{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T07:33:47Z","timestamp":1781854427031,"version":"3.54.5"},"reference-count":173,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2021,8,23]],"date-time":"2021-08-23T00:00:00Z","timestamp":1629676800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000268","name":"Biotechnology and Biological Sciences Research Council","doi-asserted-by":"publisher","award":["BB\/D001641\/1"],"award-info":[{"award-number":["BB\/D001641\/1"]}],"id":[{"id":"10.13039\/501100000268","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000268","name":"Biotechnology and Biological Sciences Research Council","doi-asserted-by":"publisher","award":["BB\/M013081\/1"],"award-info":[{"award-number":["BB\/M013081\/1"]}],"id":[{"id":"10.13039\/501100000268","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000268","name":"Biotechnology and Biological Sciences Research Council","doi-asserted-by":"publisher","award":["24\/P13277"],"award-info":[{"award-number":["24\/P13277"]}],"id":[{"id":"10.13039\/501100000268","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000268","name":"Biotechnology and Biological Sciences Research Council","doi-asserted-by":"publisher","award":["24\/B12958"],"award-info":[{"award-number":["24\/B12958"]}],"id":[{"id":"10.13039\/501100000268","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>There is an urgent need to find new antibacterial agents to combat bacterial infections, including agents that inhibit novel, hitherto unexploited targets in bacterial cells. Amongst novel targets are two-component signal transduction systems (TCSs) which are the main mechanism by which bacteria sense and respond to environmental changes. TCSs typically comprise a membrane-embedded sensory protein (the sensor histidine kinase, SHK) and a partner response regulator protein. Amongst promising targets within SHKs are those involved in environmental signal detection (useful for targeting specific SHKs) and the common themes of signal transmission across the membrane and propagation to catalytic domains (for targeting multiple SHKs). However, the nature of environmental signals for the vast majority of SHKs is still lacking, and there is a paucity of structural information based on full-length membrane-bound SHKs with and without ligand. Reasons for this lack of knowledge lie in the technical challenges associated with investigations of these relatively hydrophobic membrane proteins and the inherent flexibility of these multidomain proteins that reduces the chances of successful crystallisation for structural determination by X-ray crystallography. However, in recent years there has been an explosion of information published on (a) methodology for producing active forms of full-length detergent-, liposome- and nanodisc-solubilised membrane SHKs and their use in structural studies and identification of signalling ligands and inhibitors; and (b) mechanisms of signal sensing and transduction across the membrane obtained using sensory and transmembrane domains in isolation, which reveal some commonalities as well as unique features. Here we review the most recent advances in these areas and highlight those of potential use in future strategies for antibiotic discovery. This Review is part of a Special Issue entitled \u201cInteractions of Bacterial Molecules with Their Ligands and Other Chemical Agents\u201d edited by Mary K. Phillips-Jones.<\/jats:p>","DOI":"10.3390\/molecules26165110","type":"journal-article","created":{"date-parts":[[2021,8,23]],"date-time":"2021-08-23T10:24:17Z","timestamp":1629714257000},"page":"5110","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Membrane Sensor Histidine Kinases: Insights from Structural, Ligand and Inhibitor Studies of Full-Length Proteins and Signalling Domains for Antibiotic Discovery"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4080-2908","authenticated-orcid":false,"given":"Pikyee","family":"Ma","sequence":"first","affiliation":[{"name":"Laboratory of Biomolecular Research, Paul Scherrer Institute, CH-5232 Villigen, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary K.","family":"Phillips-Jones","sequence":"additional","affiliation":[{"name":"National Centre for Macromolecular Hydrodynamics, School of Biosciences, University of Nottingham, Sutton Bonington LE12 5RD, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,8,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"7850","DOI":"10.1073\/pnas.83.20.7850","article-title":"Two-component regulatory systems responsive to environmental stimuli share strongly conserved domains with the nitrogen assimilation regulatory genes ntrB and ntrC","volume":"83","author":"Nixon","year":"1986","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Hoch, J.A., and Silhavy, T.J. (1995). Historical Perspective. Two-Component Signal Transduction, American Society for Microbiology. Chapter 1.","DOI":"10.1128\/9781555818319"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"7024","DOI":"10.1128\/jb.175.21.7024-7032.1993","article-title":"Mechanism of autophosphorylation of Escherichia coli nitrogen regulator II (NRII or NtrB): Transphosphorylation between subunits","volume":"175","author":"Ninfa","year":"1993","journal-title":"J. Bacteriol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1111\/j.1365-2958.1993.tb01588.x","article-title":"Intermolecular complementation of the kinase activity of CheA","volume":"8","author":"Swanson","year":"1993","journal-title":"Mol. Microbiol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1016\/j.cell.2009.08.032","article-title":"Structural insight into partner specificity and phosphoryl transfer in two-component signal transduction","volume":"139","author":"Casino","year":"2009","journal-title":"Cell"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1735","DOI":"10.1128\/JB.01401-09","article-title":"The ArcB sensor kinase of Escherichia coli autophosphorylates by an intramolecular reaction","volume":"192","author":"Georgellis","year":"2010","journal-title":"J. Bacteriol."},{"key":"ref_7","unstructured":"Gross, R., and Beier, D. (2012). Structural basis of signal transduction and specificity in two-component systems. Two-Component Systems in Bacteria, Caister Academic Press. Chapter 2."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1146\/annurev-micro-102215-095331","article-title":"Feedback control of two-component regulatory systems","volume":"70","author":"Groisman","year":"2016","journal-title":"Ann. Rev. Microbiol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"3752","DOI":"10.1016\/j.jmb.2016.08.003","article-title":"Molecular mechanisms of two-component signal transduction","volume":"428","author":"Zschiedrich","year":"2016","journal-title":"J. Mol. Biol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1146\/annurev-micro-030117-020355","article-title":"A life in Bacillus subtilis signal transduction","volume":"71","author":"Hoch","year":"2017","journal-title":"Ann. Rev. Microbiol."},{"key":"ref_11","first-page":"990","article-title":"General aspects of two-component regulatory circuits in bacteria: Domains, signals and roles","volume":"18","author":"Mongradon","year":"2017","journal-title":"Curr. Protein Pep. Sci."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1016\/bs.mie.2018.04.004","article-title":"Quantitative analysis of intracellular response regulator phosphatase activity of histidine kinases","volume":"607","author":"Gao","year":"2018","journal-title":"Meth. Enzymol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1700197","DOI":"10.1002\/bies.201700197","article-title":"Transmembrane signal transduction in two-component systems: Piston, scissoring, or helical rotation?","volume":"40","author":"Gushchin","year":"2018","journal-title":"Bioessays"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1016\/S1471-4892(02)00194-7","article-title":"Two-component and phosphorelay signal-transduction systems as therapeutic targets","volume":"2","author":"Stephenson","year":"2002","journal-title":"Curr. Opin. Pharmacol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"3447","DOI":"10.1099\/mic.0.28423-0","article-title":"Genome update: Distribution of two-component transduction systems in 250 bacterial genomes","volume":"151","author":"Kiil","year":"2005","journal-title":"Microbiology"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"386","DOI":"10.1016\/S0076-6879(06)22019-6","article-title":"Targeting two-component signal transduction: A novel drug discovery system. Two-component signalling systems Part A","volume":"422","author":"Okada","year":"2007","journal-title":"Meth. Enzymol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1016\/j.mib.2010.01.008","article-title":"Two-component signal transduction as potential drug targets in pathogenic bacteria","volume":"13","author":"Gotoh","year":"2010","journal-title":"Curr. Opin. Microbiol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1002\/ddr.20362","article-title":"Bacterial protein kinase inhibitors","volume":"71","author":"Kurosu","year":"2010","journal-title":"Drug Devel. Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1248\/yakushi.132.51","article-title":"Two-component signal transduction as attractive drug targets in pathogenic bacteria","volume":"132","author":"Utsumi","year":"2012","journal-title":"Yakugaku Zasshi-J. Pharmaceut. Soc. Jpn."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1016\/j.mib.2009.12.011","article-title":"Evolution and phyletic distribution of two-component signal transduction systems","volume":"13","author":"Wuichet","year":"2010","journal-title":"Curr. Opin. Microbiol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1265","DOI":"10.4155\/fmc.13.58","article-title":"Small-molecule inhibition of bacterial two-component systems to combat antibiotic resistance and virulence","volume":"5","author":"Worthington","year":"2013","journal-title":"Future Med. Chem."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"93","DOI":"10.3103\/S0891416814030082","article-title":"Two-component bacterial regulation systems: Targets of a search for new antibacterial drugs","volume":"29","author":"Tiganova","year":"2014","journal-title":"Mol. Gen. Microbiol. Virol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1878","DOI":"10.3389\/fmicb.2017.01878","article-title":"Two-component signal transduction systems of pathogenic bacteria as targets for antimicrobial therapy: An overview","volume":"8","author":"Tiwari","year":"2017","journal-title":"Front. Microbiol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"e00681-17","DOI":"10.1128\/JB.00681-17","article-title":"Phyletic distribution and lineage-specific domain architectures of Archaeal two-component signal transduction systems","volume":"200","author":"Galperin","year":"2018","journal-title":"J. Bacteriol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"49","DOI":"10.3389\/fmicb.2019.00049","article-title":"Signal transduction proteins in Acinetobacter baumannii: Role in antibiotic resistance, virulence, and potential as drug targets","volume":"10","author":"Kumar","year":"2019","journal-title":"Front. Microbiol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1146\/annurev.micro.091208.073214","article-title":"Biological insights from structures of two-component proteins","volume":"63","author":"Gao","year":"2009","journal-title":"Ann. Rev. Microbiol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"D142","DOI":"10.1093\/nar\/gkh088","article-title":"SMART 4.0: Towards genomic data integration","volume":"32","author":"Letunic","year":"2004","journal-title":"Nucl. Acids Res."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Barakat, M., Ortet, P., Jourlin-Castelli, C., Mejean, V., and Whitworth, D.E. (2009). P2CS: A two-component system resource for prokaryotic signal transduction research. BMC Genom., 10.","DOI":"10.1186\/1471-2164-10-315"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"D401","DOI":"10.1093\/nar\/gkp940","article-title":"The MiST2 database: A comprehensive genomics resource on microbial signal transduction","volume":"38","author":"Ulrich","year":"2010","journal-title":"Nucl. Ac. Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1016\/j.mib.2010.01.005","article-title":"Diversity of structure and function of response regulator output domains","volume":"13","author":"Galperin","year":"2010","journal-title":"Curr. Opin. Microbiol."},{"key":"ref_31","unstructured":"Gross, R., and Beier, D. (2012). Classification and organisation of two-component systems. Two-Component Systems in Bacteria, Caister Academic Press. Chapter 1."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1448","DOI":"10.1074\/jbc.M410104200","article-title":"Functional characterization in vitro of all two-component signal transduction systems from Escherichia coli","volume":"280","author":"Yamamoto","year":"2005","journal-title":"J. Biol. Chem."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"5819","DOI":"10.1128\/JB.184.21.5819-5825.2002","article-title":"Two-Component signal transduction in Enterococcus faecalis","volume":"184","author":"Hancock","year":"2002","journal-title":"J. Bacteriol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1080\/09687680802359885","article-title":"Expression, purification and activities of the entire family of intact membrane sensor kinases from Enterococcus faecalis","volume":"25","author":"Ma","year":"2008","journal-title":"Mol. Membr. Biol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"14240","DOI":"10.1073\/pnas.0403302101","article-title":"Genomic plasticity of the causative agent of melioidosis, Burkholderia pseudomallei","volume":"101","author":"Holden","year":"2004","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"959","DOI":"10.1038\/35023079","article-title":"Complete genome sequence of Pseudomonas aeruginosa PAO1, an opportunistic pathogen","volume":"406","author":"Stover","year":"2000","journal-title":"Nature"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1038\/nature01586","article-title":"The genome sequence of Bacillus anthracis Ames and comparison to closely related bacteria","volume":"423","author":"Read","year":"2003","journal-title":"Nature"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1453","DOI":"10.1126\/science.277.5331.1453","article-title":"The complete genome sequence of Escherichia coli K-12","volume":"277","author":"Blattner","year":"1997","journal-title":"Science"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1038\/31159","article-title":"Deciphering the biology of Mycobacterium tuberculosis from the complete genome sequence","volume":"393","author":"Cole","year":"1998","journal-title":"Nature"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1038\/ng1227","article-title":"Comparative analysis of the genome sequences of Bordetella pertussis, Bordetella parapertussis and Bordetella bronchiseptica","volume":"35","author":"Parkhill","year":"2003","journal-title":"Nat. Genet."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"601","DOI":"10.1101\/gad.1510307","article-title":"New insights into Acinetobacter baumannii pathogenesis revealed by high-density pyrosequencing and transposon mutagenesis","volume":"21","author":"Smith","year":"2007","journal-title":"Genes Devel."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"8053","DOI":"10.1128\/JB.00834-08","article-title":"Comparative genome sequence analysis of multidrug-resistant Acinetobacter Baumannii","volume":"190","author":"Adams","year":"2008","journal-title":"J. Bacteriol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"2071","DOI":"10.1126\/science.1080613","article-title":"Role of mobile DNA in the evolution of vancomycin-resistant Enterococcus faecalis","volume":"299","author":"Paulsen","year":"2003","journal-title":"Science"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1073\/pnas.221575398","article-title":"The genome sequence of the facultative intracellular pathogen Brucella melitensis","volume":"99","author":"DelVecchio","year":"2002","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"2715","DOI":"10.1128\/JB.187.8.2715-2726.2005","article-title":"Completion of the genome sequence of Brucella abortus and comparison to the highly similar genomes of Brucella melitensis and Brucella suis","volume":"187","author":"Halling","year":"2005","journal-title":"J. Bacteriol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"996","DOI":"10.1073\/pnas.022493799","article-title":"Complete genome sequence of Clostridium perfringens, an anaerobic flesh-eater","volume":"99","author":"Shimizu","year":"2002","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1225","DOI":"10.1016\/S0140-6736(00)04403-2","article-title":"Whole genome sequencing of methicillin-resistant Staphylococcus aureus","volume":"357","author":"Kuroda","year":"2001","journal-title":"Lancet"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1499","DOI":"10.1046\/j.1365-2958.2002.03126.x","article-title":"Genome sequence of Streptococcus agalactiae, a pathogen causing invasive neonatal disease","volume":"45","author":"Glaser","year":"2002","journal-title":"Mol. Microbiol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"e00931-19","DOI":"10.1128\/IAI.00931-19","article-title":"Two-component signal transduction systems in the human pathogen Streptococcus agalactiae","volume":"88","author":"Thomas","year":"2020","journal-title":"Infect. Immun."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1016\/S0378-1119(99)00266-8","article-title":"Domain organization and molecular characterization of 13 two-component systems identified by genome sequencing of Streptococcus pneumoniae","volume":"237","author":"Lange","year":"1999","journal-title":"Gene"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1089\/10766290152044995","article-title":"Annotated draft genomic sequence from a Streptococcus pneumoniae type 19F clinical isolate","volume":"7","author":"Dopazo","year":"2001","journal-title":"Microb. Drug Res."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"4658","DOI":"10.1073\/pnas.071559398","article-title":"Complete genome sequence of an M1 strain of Streptococcus pyogenes","volume":"98","author":"Ferretti","year":"2001","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"496","DOI":"10.1126\/science.7542800","article-title":"Whole-genome random sequencing and assembly of Haemophilus influenzae Rd","volume":"269","author":"Fleischmann","year":"1995","journal-title":"Science"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1038\/41483","article-title":"The complete genome sequence of the gastric pathogen Helicobacter pylori","volume":"388","author":"Tomb","year":"1997","journal-title":"Nature"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"665","DOI":"10.1038\/35001088","article-title":"The genome sequence of the food-borne pathogen Campylobacter jejuni reveals hypervariable sequences","volume":"403","author":"Parkhill","year":"2000","journal-title":"Nature"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1126\/science.270.5235.397","article-title":"The minimal gene complement of Mycoplasma genitalium","volume":"270","author":"Fraser","year":"1995","journal-title":"Science"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"2819","DOI":"10.1099\/mic.0.26460-0","article-title":"Transcriptional regulation of efflux genes by EvgAS, a two-component system in Escherichia coli","volume":"149","author":"Eguchi","year":"2003","journal-title":"Microbiology"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"2068","DOI":"10.1128\/JB.182.8.2068-2076.2000","article-title":"Molecular characterization of two-component systems of Helicobacter pylori","volume":"182","author":"Beier","year":"2000","journal-title":"J. Bacteriol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"6375","DOI":"10.1128\/JB.180.23.6375-6383.1998","article-title":"A two-component signal transduction system essential for growth of Bacillus subtilis: Implications for anti-infective therapy","volume":"180","author":"Fabret","year":"1998","journal-title":"J. Bacteriol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"741","DOI":"10.1080\/09168451.2018.1444466","article-title":"Essentiality and function of WalK\/WalR two-component system: The past, present, and future of research","volume":"82","author":"Takada","year":"2018","journal-title":"Biosci. Biotechol. Biochem."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1440","DOI":"10.1002\/med.21651","article-title":"Synthesis of histidine kinase inhibitors and their biological properties","volume":"40","author":"Meffre","year":"2020","journal-title":"Med. Res. Rev."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1016\/j.jbiotec.2020.04.014","article-title":"Inhibition of biofilm and biofilm-associated virulence factor production in methicillin-resistant Staphylococcus aureus by docosanol","volume":"317","author":"Lakshmi","year":"2020","journal-title":"J. Biotechol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"793","DOI":"10.1016\/j.chembiol.2020.04.005","article-title":"Targeting two-component systems uncovers a small-molecule inhibitor of Salmonella virulence","volume":"27","author":"Tsai","year":"2020","journal-title":"Cell Chem. Biol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"457","DOI":"10.4155\/fmc-2019-0263","article-title":"Inhibiting DosRST as a new approach to tuberculosis therapy","volume":"12","author":"Zheng","year":"2020","journal-title":"Future Med. Chem."},{"key":"ref_65","first-page":"e01744-19","article-title":"Quinazoline-based antivirulence compounds selectively target Salmonella PhoP\/PhoQ signal transduction system","volume":"64","author":"Asquith","year":"2020","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Hirakawa, H., Kurushima, J., Hashimoto, Y., and Tomita, H. (2020). Progress overview of bacterial two-component regulatory systems as potential targets for antimicrobial chemotherapy. Antibiotics, 9.","DOI":"10.3390\/antibiotics9100635"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1127","DOI":"10.1016\/j.str.2013.04.024","article-title":"Full-length structure of a sensor histidine kinase pinpoints coaxial coiled coils as signal transducers and modulators","volume":"21","author":"Diensthuber","year":"2013","journal-title":"Structure"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"17839","DOI":"10.1073\/pnas.1413983111","article-title":"Full-length structure of a monomeric histidine kinase reveals basis for sensory regulation","volume":"111","author":"Ko","year":"2014","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_69","first-page":"39","article-title":"Crystallization and initial X-ray diffraction analysis of the multidomain Brucella blue light-activated histidine kinase LOV-HK in its illuminated state","volume":"16","author":"Rinaldi","year":"2018","journal-title":"Biochem. Biophys. Rep."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"eaaq0825","DOI":"10.1126\/scisignal.aaq0825","article-title":"Architecture of the complete oxygen-sensing FixL-FixJ two-component signal transduction system","volume":"11","author":"Wright","year":"2018","journal-title":"Sci. Signal."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1923","DOI":"10.1002\/pro.3705","article-title":"Signal transduction in photoreceptor histidine kinases","volume":"28","author":"Moeglich","year":"2019","journal-title":"Protein Sci."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"e00264-21","DOI":"10.1128\/mBio.00264-21","article-title":"Dimer asymmetry and light activation mechanism in Brucella blue-light sensor histidine kinase","volume":"12","author":"Rinaldi","year":"2021","journal-title":"MBio"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1016\/j.bbamem.2013.07.010","article-title":"Membrane protein structure determination-the next generation","volume":"1838","author":"Moraes","year":"2014","journal-title":"Biochim. Biophys. Acta Biomembr."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1595","DOI":"10.1016\/j.bbamem.2012.02.015","article-title":"Interactions of the intact FsrC membrane histidine kinase with its pheromone ligand GBAP revealed through synchrotron radiation circular dichroism","volume":"1818","author":"Patching","year":"2012","journal-title":"Biochim. Biophys. Acta Biomembr."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"46180","DOI":"10.1038\/srep46180","article-title":"Hydrodynamics of the VanA-type VanS histidine kinase: An extended solution conformation and first evidence for interactions with vancomycin","volume":"7","author":"Channell","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"2660","DOI":"10.1016\/j.febslet.2011.07.026","article-title":"Anti-HIV siamycin I directly inhibits autophosphorylation activity of the bacterial FsrC quorum sensor and other ATP-dependent enzyme activities","volume":"585","author":"Ma","year":"2011","journal-title":"FEBS Lett."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"4368","DOI":"10.1021\/acs.biochem.8b00485","article-title":"Exploration of the effects of \u03b3-phosphate-modified ATP analogues on histidine kinase autophosphorylation","volume":"57","author":"Chase","year":"2018","journal-title":"Biochemistry"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"113765","DOI":"10.1016\/j.ab.2020.113765","article-title":"An immuno-dot blot assay for screening histidine kinase inhibitors","volume":"600","author":"Maruta","year":"2020","journal-title":"Anal. Biochem."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"1078","DOI":"10.1126\/science.1160354","article-title":"Targeting QseC signaling and virulence for antibiotic development","volume":"321","author":"Rasko","year":"2008","journal-title":"Science"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"4436","DOI":"10.1128\/AAC.00719-15","article-title":"The carbonic anhydrase inhibitor ethoxzolamide inhibits the Mycobacterium tuberculosis PhoPR regulon and Esx-1 secretion and attenuates virulence","volume":"59","author":"Johnson","year":"2015","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1038\/nchembio.2259","article-title":"Inhibitors of Mycobacterium tuberculosis DosRST signaling and persistence","volume":"13","author":"Zheng","year":"2017","journal-title":"Nat. Chem. Biol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"5322","DOI":"10.1016\/j.bmc.2018.04.047","article-title":"Screening serine\/threonine and tyrosine kinase inhibitors for histidine kinase inhibition","volume":"26","author":"Wilke","year":"2018","journal-title":"Bioorg. Med. Chem."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1021\/acschembio.8b00849","article-title":"Inhibiting Mycobacterium tuberculosis DosRST signaling by targeting response regulator DNA binding and sensor kinase heme","volume":"15","author":"Zheng","year":"2019","journal-title":"ACS Chem. Biol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"1358","DOI":"10.1128\/JB.00969-06","article-title":"Siamycin attenuates fsr quorum sensing mediated by a gelatinase biosynthesis-activating pheromone in Enterococcus faecalis","volume":"189","author":"Nakayama","year":"2007","journal-title":"J. Bacteriol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"7332","DOI":"10.1039\/C8SC02496K","article-title":"Disarming the virulence arsenal of Pseudomonas aeruginosa by blocking two-component system signalling","volume":"9","author":"Goswami","year":"2018","journal-title":"Chem. Sci."},{"key":"ref_86","doi-asserted-by":"crossref","unstructured":"Qin, Z., Zhang, J., Xu, B., Chen, L., Wu, Y., Yang, X., Shen, X., Molin, S., Danchin, A., and Jiang, H. (2006). Structure-based discovery of inhibitors of the YycG histidine kinase: New chemical leads to combat Staphylococcus epidermidis infections. BMC Microbiol., 6.","DOI":"10.1186\/1471-2180-6-96"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1016\/S0022-2836(02)00424-2","article-title":"Expression, purification and characterisation of full-length heterologously expressed histidine protein kinase RegB from Rhodobacter sphaeroides","volume":"320","author":"Potter","year":"2002","journal-title":"J. Mol. Biol."},{"key":"ref_88","unstructured":"Baldwin, S.A. (1999). The amplified expression, identification, purification, assay and properties of hexahistidine-tagged bacterial membrane transport proteins. Membrane Transport\u2014A Practical Approach, Oxford University Press."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1007\/s12551-018-0404-9","article-title":"Antimicrobial resistance (AMR) nanomachines-mechanisms for fluoroquinolone and glycopeptide recognition, efflux and deactivation","volume":"10","author":"Harding","year":"2018","journal-title":"Biophys. Rev."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"723","DOI":"10.1007\/s00249-018-1325-z","article-title":"Production of membrane proteins for characterisation of their pheromone-sensing and antimicrobial resistance functions","volume":"47","author":"Azam","year":"2018","journal-title":"Eur. Biophys. J."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"3206","DOI":"10.1016\/j.febslet.2006.04.079","article-title":"Redox-responsive in vitro modulation of the signalling state of the isolated PrrB sensor kinase of Rhodobacter sphaeroides NCIB 8253","volume":"580","author":"Potter","year":"2006","journal-title":"FEBS Lett."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"7915","DOI":"10.1021\/bi0496440","article-title":"Reconstitution of the Rhodobacter sphaeroides cbb3-PrrBA signal transduction pathway in vitro","volume":"43","author":"Oh","year":"2004","journal-title":"Biochemistry"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"1074","DOI":"10.1073\/pnas.82.4.1074","article-title":"A bacteriophage T7 RNA polymerase\/promoter system for controlled exclusive expression of specific genes","volume":"82","author":"Tabor","year":"1985","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"5727","DOI":"10.1038\/s41598-020-62557-z","article-title":"The extracellular domain of two-component system sensor kinase VanS from Streptomyces coelicolor binds vancomycin at a newly identified binding site","volume":"10","author":"Lockey","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_95","doi-asserted-by":"crossref","unstructured":"Upton, E.C., Maciunas, L.J., and Loll, P.J. (2019). Vancomycin does not affect the enzymatic activities of purified VanSA. PLoS ONE, 14.","DOI":"10.1371\/journal.pone.0210627"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1016\/j.pep.2006.12.006","article-title":"Ligation independent cloning vectors for expression of SUMO fusions","volume":"53","author":"Weeks","year":"2007","journal-title":"Protein Expr. Purif."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"867","DOI":"10.1042\/BST0330867","article-title":"Active membrane transport and receptor proteins from bacteria","volume":"33","author":"Saidijam","year":"2005","journal-title":"Biochem. Soc. Trans."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"3329","DOI":"10.1128\/JB.188.9.3329-3336.2006","article-title":"The hydantoin transport protein from Microbacterium liquefaciens","volume":"188","author":"Suzuki","year":"2006","journal-title":"J. Bacteriol."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"2178","DOI":"10.1110\/ps.062312706","article-title":"Comparative analysis and \u2018\u2018expression space\u2019\u2019 coverage of the production of prokaryotic membrane proteins for structural genomics","volume":"15","author":"Surade","year":"2006","journal-title":"Protein Sci."},{"key":"ref_100","unstructured":"Ma, P. (2010). Structure-Activity Relationships of Membrane Proteins: The NCS1 Family of Transporters and Sensor Kinases of Two-Component Systems. [Ph.D. Thesis, University of Leeds]."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/S0076-6879(03)72004-7","article-title":"Reconstitution of membrane proteins into liposomes","volume":"372","author":"Rigaud","year":"2003","journal-title":"Meth. Enzymol."},{"key":"ref_102","doi-asserted-by":"crossref","unstructured":"T\u00fcrck, M., and Bierbaum, G. (2012). Purification and activity testing of the full-length YycFGHI proteins of Staphylococcus aureus. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0030403"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"13954","DOI":"10.1021\/bi0616706","article-title":"Amphipathic polymers: Tools to fold integral membrane proteins to their active form","volume":"45","author":"Pocanschi","year":"2006","journal-title":"Biochemistry"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1016\/S0076-6879(07)23014-9","article-title":"Using nanodiscs to create water-soluble transmembrane chemoreceptors inserted in lipid bilayers","volume":"423","author":"Boldog","year":"2007","journal-title":"Meth. Enzymol."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"809","DOI":"10.1016\/j.bbamem.2017.08.012","article-title":"Structure and function of membrane proteins encapsulated in a polymer-bound lipid bilayer","volume":"1860","author":"Pollock","year":"2018","journal-title":"Biochim. Biophys. Acta Biomembr."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1016\/j.sbi.2021.03.008","article-title":"Structural biology of endogenous membrane protein assemblies in native nanodiscs","volume":"69","author":"Brown","year":"2021","journal-title":"Curr. Opin. Struct. Biol."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"929","DOI":"10.1016\/j.molcel.2014.02.029","article-title":"Activation and inhibition of the receptor histidine kinase AgrC occurs through opposite helical transduction motions","volume":"53","author":"Wang","year":"2014","journal-title":"Mol. Cell."},{"key":"ref_108","doi-asserted-by":"crossref","unstructured":"Hoernschemeyer, P., Liss, V., Heermann, R., Jung, K., and Hunke, S. (2016). Interaction analysis of a two-component system using nanodiscs. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0149187"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1042\/BCJ20180577","article-title":"Mechanism of metal ion-induced activation of a two-component sensor kinase","volume":"476","author":"Affandi","year":"2019","journal-title":"Biochem. J."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"e01295-19","DOI":"10.1128\/mBio.01295-19","article-title":"Cryo-electron microscopy structure of an Acinetobacter baumannii multidrug efflux pump","volume":"10","author":"Su","year":"2019","journal-title":"MBio"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"5665","DOI":"10.1016\/j.jmb.2020.08.017","article-title":"The multidrug transporter MdfA deviates from the canonical model of alternating access of MFS transporters","volume":"432","author":"Yardeni","year":"2020","journal-title":"J. Mol. Biol."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"183191","DOI":"10.1016\/j.bbamem.2020.183191","article-title":"Solution structure and oligomeric state of the E. coli glycerol facilitator","volume":"1862","author":"Hernando","year":"2020","journal-title":"Biochim. Biophys. Acta. Biomembr."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1016\/j.bpj.2019.11.3381","article-title":"Folding of the \u03b2-Barrel membrane protein OmpA into nanodiscs","volume":"118","author":"Asamoto","year":"2020","journal-title":"Biophys. J."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"7786","DOI":"10.1021\/acs.analchem.0c00917","article-title":"Detergent titration as an efficient method for NMR resonance assignments of membrane proteins in lipid-bilayer nanodiscs","volume":"92","author":"Bibow","year":"2020","journal-title":"Anal. Chem."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"15227","DOI":"10.1038\/s41598-017-15151-9","article-title":"Polymer nanodiscs: Discoidal amphiphilic block copolymer membranes as a new platform for membrane proteins","volume":"7","author":"Fiori","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"1951","DOI":"10.1016\/j.bbamem.2017.06.017","article-title":"Modulation of protein function in membrane mimetics: Characterization of P. denitrificans cNOR in nanodiscs or liposomes","volume":"1859","author":"Kahle","year":"2017","journal-title":"Biochim. Biophys. Acta Biomembr."},{"key":"ref_117","doi-asserted-by":"crossref","unstructured":"Liu, Y., Moura, E.C.C.M., D\u00f6rr, J.M., Scheidelaar, S., Heger, M., Egmond, M.R., Killian, J.A., Mohammadi, T., and Breukink, E. (2018). Bacillus subtilis MraY in detergent-free system of nanodiscs wrapped by styrene-maleic acid copolymers. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0210135"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"1000","DOI":"10.1177\/1087057114520975","article-title":"Overview of recent progress in protein-expression technologies for small-molecule screening","volume":"19","author":"Cuozzo","year":"2014","journal-title":"J. Biomol. Screen."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1046\/j.1365-2958.2001.02486.x","article-title":"Gelatinase biosynthesis-activating pheromone: A peptide lactone that mediates a quorum sensing in Enterococcus faecalis","volume":"41","author":"Nakayama","year":"2001","journal-title":"Mol. Microbiol."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"2579","DOI":"10.1128\/IAI.68.5.2579-2586.2000","article-title":"Effects of Enterococcus faecalis fsr genes on production of gelatinase and a serine protease and virulence","volume":"68","author":"Qin","year":"2000","journal-title":"Infect. Immun."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"3372","DOI":"10.1128\/JB.183.11.3372-3382.2001","article-title":"Characterization of fsr, a regulator controlling expression of gelatinase and serine protease in Enterococcus faecalis OG1RF","volume":"183","author":"Qin","year":"2001","journal-title":"J. Bacteriol."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"5629","DOI":"10.1128\/JB.186.17.5629-5639.2004","article-title":"The Enterococcus faecalis fsr two-component system controls biofilm development through production of gelatinase","volume":"186","author":"Hancock","year":"2004","journal-title":"J. Bacteriol."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"967","DOI":"10.1086\/423139","article-title":"Effects of glucose on fsr-mediated biofilm formation in Enterococcus faecalis","volume":"190","author":"Pillai","year":"2004","journal-title":"J. Infect. Dis."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"444","DOI":"10.1039\/C2CP43722H","article-title":"Interactions of the intact FsrC membrane histidine kinase with the tricyclic peptide siamycin I revealed through synchrotron radiation circular dichroism","volume":"15","author":"Patching","year":"2013","journal-title":"Phys. Chem. Chem. Phys."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1128\/AAC.40.1.133","article-title":"Characterization of siamycin I, a human immunodeficiency virus fusion inhibitor","volume":"40","author":"Lin","year":"1996","journal-title":"Antimicr. Agents Chemother."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"433","DOI":"10.7164\/antibiotics.48.433","article-title":"Siamycins I and II, new anti-HIV peptides: I. Fermentation, isolation, biological activity and initial characterization","volume":"48","author":"Tsunakawa","year":"1995","journal-title":"J. Antibiot."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"5917","DOI":"10.1021\/bi0340595","article-title":"Identification of basic amino acids important for citrate binding by the periplasmic receptor domain of the sensor kinase CitA","volume":"42","author":"Gerharz","year":"2003","journal-title":"Biochem."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"2582","DOI":"10.1128\/jb.174.8.2582-2591.1992","article-title":"The VanS-VanR two-component regulatory system controls synthesis of depsipeptide peptidoglycan precursors in Enterococcus faecium BM4147","volume":"174","author":"Arthur","year":"1992","journal-title":"J. Bacteriol."},{"key":"ref_129","unstructured":"Utsumi, R. (2008). Vancomycin resistance VanS\/VanR two-component systems. Bacterial Signal Transduction: Networks and Drug Targets, Landes Bioscience & Springer Science & Business Media."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"686","DOI":"10.1128\/CMR.13.4.686","article-title":"Vancomycin-resistant enterococci","volume":"13","author":"Cetinkaya","year":"2000","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1016\/j.ijmm.2004.10.002","article-title":"Genetics of glycopeptide resistance in Gram-positive pathogens","volume":"294","author":"Courvalin","year":"2005","journal-title":"Int. J. Med. Microbiol."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"1645","DOI":"10.1128\/AAC.40.7.1645","article-title":"Induction signals for vancomycin resistance encoded by the vanA gene cluster in Enterococcus faecium","volume":"40","author":"Lai","year":"1996","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"2291","DOI":"10.1128\/AAC.40.10.2291","article-title":"Specificity of induction of glycopeptide resistance genes in Enterococcus faecalis","volume":"40","author":"Baptista","year":"1996","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"1951","DOI":"10.1016\/j.bbagen.2017.05.011","article-title":"Characterisation of the selective binding of antibiotics vancomycin and teicoplanin by the VanS receptor regulating type A vancomycin resistance in the enterococci","volume":"1861","author":"Hughes","year":"2017","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1128\/jb.179.1.97-106.1997","article-title":"The VanS sensor negatively controls VanR-mediated transcriptional activation of glycopeptide resistance genes of Tn1546 and related elements in the absence of induction","volume":"179","author":"Arthur","year":"1997","journal-title":"J. Bacteriol."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1046\/j.1365-2958.1999.01308.x","article-title":"Single-cell analysis of glycopeptide resistance gene expression in teicoplanin-resistant mutants of a VanB-type Enterococcus faecalis","volume":"32","author":"Baptista","year":"1999","journal-title":"Mol. Microbiol."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1128\/AAC.45.2.375-381.2001","article-title":"Regulation of VanA- and VanB-type glycopeptide resistance in enterococci","volume":"45","author":"Arthur","year":"2001","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1038\/nchembio.350","article-title":"A vancomycin photoprobe identifies the histidine kinase VanSsc as a vancomycin receptor","volume":"6","author":"Koteva","year":"2010","journal-title":"Nat. Chem. Biol."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"4470","DOI":"10.1128\/AAC.00523-13","article-title":"In vivo studies suggest that induction of VanS-dependent vancomycin resistance requires binding of the drug to D-Ala-D-Ala termini in the peptidoglycan cell wall","volume":"57","author":"Novotna","year":"2013","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"1302","DOI":"10.1128\/jb.178.5.1302-1309.1996","article-title":"Regulation of VanB-type vancomycin resistance gene expression by the VanSB-VanRB two-component regulatory system in Enterococcus faecalis V583","volume":"178","author":"Evers","year":"1996","journal-title":"J. Bacteriol."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"4831","DOI":"10.1128\/JB.00301-08","article-title":"Role of the global transcriptional regulator PrrA in Rhodobacter sphaeroides 2.4.1: Combined transcriptome and proteome analysis","volume":"190","author":"Eraso","year":"2008","journal-title":"J. Bacteriol."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"6654","DOI":"10.1128\/JB.184.23.6654-6664.2002","article-title":"Differential expression of the CO2 fixation operons of Rhodobacter sphaeroides by the Prr\/Reg two-component system during chemoautotrophic growth","volume":"184","author":"Gibson","year":"2002","journal-title":"J. Bacteriol."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"6778","DOI":"10.1093\/nar\/gkg891","article-title":"Solution structure and DNA binding of the effector domain from the global regulator PrrA (RegA) from Rhodobacter sphaeroides: Insights into DNA binding specificity","volume":"31","author":"Laguri","year":"2003","journal-title":"Nucl. Acids Res."},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"26840","DOI":"10.1016\/j.ijhydene.2020.07.108","article-title":"The adherence-associated Fdp fasciclin I domain protein of the biohydrogen producer Rhodobacter sphaeroides is regulated by the global Prr pathway","volume":"45","author":"Jeong","year":"2020","journal-title":"Int. J. Hydr. Energ."},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"4044","DOI":"10.1128\/JB.180.16.4044-4050.1998","article-title":"A redox-responsive pathway for aerobic regulation of photosynthesis gene expression in Rhodobacter sphaeroides 2.4.1","volume":"180","author":"Eraso","year":"1998","journal-title":"J. Bacteriol."},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"2688","DOI":"10.1021\/bi9825100","article-title":"The cbb(3) terminal oxidase of Rhodobacter sphaeroides 2.4.1: Structural and functional implications for the regulation of spectral complex formation","volume":"38","author":"Oh","year":"1999","journal-title":"Biochem."},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"4237","DOI":"10.1093\/emboj\/19.16.4237","article-title":"Redox signalling: Globalization of gene expression","volume":"19","author":"Oh","year":"2000","journal-title":"EMBO J."},{"key":"ref_148","doi-asserted-by":"crossref","unstructured":"Gajdiss, M., Monk, I.R., Bertsche, U., Kienemund, J., Funk, T., Dietrich, A., Hort, M., Sib, E., Stinear, T.P., and Bierbaum, G. (2020). YycH and YycI regulate expression of Staphylococcus aureus autolysins by activation of WalRK phosphorylation. Microorganisms, 8.","DOI":"10.3390\/microorganisms8060870"},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"1573","DOI":"10.1099\/00221287-146-7-1573","article-title":"The essential two-component regulatory system encoded by yycF and yycG modulates expression of the ftsAZ operon in Bacillus subtilis","volume":"146","author":"Fukuchi","year":"2000","journal-title":"Microbiology"},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1111\/j.1365-2958.2007.05782.x","article-title":"The essential YycFG two-component system controls cell wall metabolism in Bacillus subtilis","volume":"65","author":"Bisicchia","year":"2007","journal-title":"Mol. Microbiol."},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"1639","DOI":"10.1046\/j.1365-2958.2003.03661.x","article-title":"Genes controlled by the essential YycG\/YycF two-component system of Bacillus subtilis revealed through a novel hybrid regulator approach","volume":"49","author":"Howell","year":"2003","journal-title":"Mol. Microbiol."},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"3666","DOI":"10.1128\/JB.181.12.3666-3673.1999","article-title":"Role in cell permeability of an essential two-component system in Staphylococcus aureus","volume":"181","author":"Martin","year":"1999","journal-title":"J. Bacteriol."},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"8257","DOI":"10.1128\/JB.00645-07","article-title":"New insights into the WalK\/WalR (YycG\/YycF) essential signal transduction pathway reveal a major role in controlling cell wall metabolism and biofilm formation in Staphylococcus aureus","volume":"189","author":"Dubrac","year":"2007","journal-title":"J. Bacteriol."},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1111\/j.1365-2958.2008.06308.x","article-title":"A sensor histidine kinase coordinates cell wall architecture with cell division in Bacillus subtilis","volume":"69","author":"Fukushima","year":"2008","journal-title":"Mol. Microbiol."},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1111\/j.1365-2958.2010.07464.x","article-title":"A role for the essential YycG sensor histidine kinase in sensing cell division","volume":"79","author":"Fukushima","year":"2011","journal-title":"Mol. Microbiol."},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"5419","DOI":"10.1128\/JB.187.15.5419-5426.2005","article-title":"YycH regulates the activity of the essential YycFG two-component system in Bacillus subtilis","volume":"187","author":"Szurmant","year":"2005","journal-title":"J. Bacteriol."},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"3280","DOI":"10.1128\/JB.01936-06","article-title":"YycH and YycI interact to regulate the essential YycFG two-component system in Bacillus subtilis","volume":"189","author":"Szurmant","year":"2007","journal-title":"J. Bacteriol."},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"30823","DOI":"10.1038\/srep30823","article-title":"Vancomycin susceptibility in methicillin-resistant Staphylococcus aureus is mediated by YycHI activation of the WalRK essential two-component regulatory system","volume":"6","author":"Cameron","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_159","doi-asserted-by":"crossref","unstructured":"Poupel, O., Moyat, M., Groizeleau, J., Antunes, L.C.S., Gribaldo, S., Msadek, T., and Dubrac, S. (2016). Transcriptional analysis and subcellular protein localization reveal specific features of the essential WalKR system in Staphylococcus aureus. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0151449"},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"3477","DOI":"10.1021\/ja0393574","article-title":"Directed self-assembly of monodisperse phospholipid bilayer Nanodiscs with controlled size","volume":"126","author":"Denisov","year":"2004","journal-title":"J. Amer. Chem. Soc."},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"524","DOI":"10.1186\/1471-2164-14-524","article-title":"Reductive evolution and the loss of PDC\/PAS domains from the genus Staphylococcus","volume":"14","author":"Shah","year":"2013","journal-title":"BMC Genom."},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"512","DOI":"10.1016\/j.jmb.2008.01.024","article-title":"A ligand-induced switch in the periplasmic domain of sensor histidine kinase CitA","volume":"377","author":"Sevvana","year":"2008","journal-title":"J. Mol. Biol."},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"3115","DOI":"10.1073\/pnas.1620286114","article-title":"Sensory domain contraction in histidine kinase CitA triggers transmembrane signalling in the membrane-bound sensor","volume":"114","author":"Salvi","year":"2017","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1016\/j.str.2008.12.013","article-title":"Structural analysis of ligand stimulation of the histidine kinase NarX","volume":"17","author":"Cheung","year":"2009","journal-title":"Structure"},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"eaah6345","DOI":"10.1126\/science.aah6345","article-title":"Mechanism of transmembrane signaling by sensor histidine kinases","volume":"356","author":"Gushchin","year":"2017","journal-title":"Science"},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"30433","DOI":"10.1073\/pnas.1912080117","article-title":"Interface switch mediates signal transmission in a two-component system","volume":"117","author":"Wang","year":"2020","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"981","DOI":"10.1016\/j.str.2015.04.002","article-title":"Signal transduction in histidine kinases: Insights from new structures","volume":"23","author":"Bhate","year":"2015","journal-title":"Structure"},{"key":"ref_168","doi-asserted-by":"crossref","unstructured":"Gushchin, I., Orekhov, P., Melnikov, I., Polovinkin, V., Yuzhakova, A., and Gordeliy, V. (2020). Sensor histidine kinase NarQ activates via helical rotation, diagonal scissoring, and eventually piston-like shifts. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21093110"},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"1539","DOI":"10.1016\/j.cub.2010.06.074","article-title":"Membrane thickness cue for cold sensing in a bacterium","volume":"20","author":"Cybulski","year":"2010","journal-title":"Curr. Biol."},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"e02564-19","DOI":"10.1128\/mBio.02564-19","article-title":"Transmembrane prolines mediate signal sensing and decoding in Bacillus subtilis DesK histidine kinase","volume":"10","author":"Porrini","year":"2019","journal-title":"MBio"},{"key":"ref_171","doi-asserted-by":"crossref","first-page":"8141","DOI":"10.1073\/pnas.1003166107","article-title":"Transmembrane polar interactions are required for signaling in the Escherichia coli sensor kinase PhoQ","volume":"107","author":"Goldberg","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_172","doi-asserted-by":"crossref","unstructured":"Lemmin, T., Soto, C.S., Clinthorne, G., DeGrado, W.F., and Dal Peraro, M. (2013). Assembly of the transmembrane domain of E. coli PhoQ histidine kinase: Implications for signal transduction from molecular simulations. PLoS Comput. Biol., 9.","DOI":"10.1371\/journal.pcbi.1002878"},{"key":"ref_173","doi-asserted-by":"crossref","first-page":"5891","DOI":"10.1073\/pnas.0800247105","article-title":"An essential sensor histidine kinase controlled by transmembrane helix interactions with its auxiliary proteins","volume":"105","author":"Szurmant","year":"2008","journal-title":"Proc. Natl. Acad. Sci. USA"}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/26\/16\/5110\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T06:49:58Z","timestamp":1760165398000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/26\/16\/5110"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,8,23]]},"references-count":173,"journal-issue":{"issue":"16","published-online":{"date-parts":[[2021,8]]}},"alternative-id":["molecules26165110"],"URL":"https:\/\/doi.org\/10.3390\/molecules26165110","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,8,23]]}}}