{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,18]],"date-time":"2026-01-18T00:34:46Z","timestamp":1768696486489,"version":"3.49.0"},"reference-count":55,"publisher":"Public Library of Science (PLoS)","issue":"11","license":[{"start":{"date-parts":[[2016,11,29]],"date-time":"2016-11-29T00:00:00Z","timestamp":1480377600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Italian Cystic Fibrosis Foundation (adopted by Gruppo di Sostegno FFC di Como Dongo, Delegazione FFC di Olbia Tempio, Delegazione FFC di Reggio Calabria)","award":["FFC#19\/2015"],"award-info":[{"award-number":["FFC#19\/2015"]}]},{"name":"Career Development Award, Armenise-Harvard Foundation"},{"name":"Rita Levi-Montalcini award, Italian Ministry of University and Education"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"DOI":"10.1371\/journal.pone.0167350","type":"journal-article","created":{"date-parts":[[2016,11,29]],"date-time":"2016-11-29T18:36:24Z","timestamp":1480444584000},"page":"e0167350","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":16,"title":["Biochemical Characterization of Glutamate Racemase\u2014A New Candidate Drug Target against Burkholderia cenocepacia Infections"],"prefix":"10.1371","volume":"11","author":[{"given":"Aygun","family":"Israyilova","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Silvia","family":"Buroni","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Federico","family":"Forneris","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Viola Camilla","family":"Scoffone","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Namiq Q.","family":"Shixaliyev","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giovanna","family":"Riccardi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0348-9764","authenticated-orcid":true,"given":"Laurent Roberto","family":"Chiarelli","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2016,11,29]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1016\/j.jcf.2012.10.004","article-title":"Treatment of lung infection in patients with cystic fibrosis: current and future strategies","volume":"11","author":"G D\u00f6ring","year":"2012","journal-title":"J Cyst Fibros"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1097\/MCP.0b013e32835f1afc","article-title":"Respiratory bacterial infections in cystic fibrosis","volume":"19","author":"O Ciofu","year":"2013","journal-title":"Curr Opin Pulm Med"},{"key":"ref3","first-page":"CD009529","article-title":"Antibiotic treatment for <italic>Burkholderia cepacia<\/italic> complex in people with cystic fibrosis experiencing a pulmonary exacerbation","volume":"10","author":"A Horsley","year":"2012","journal-title":"Cochrane Database Syst Rev"},{"key":"ref4","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1186\/s12890-015-0148-2","article-title":"<italic>Burkholderia cepacia<\/italic> complex: clinical course in cystic fibrosis patients","volume":"15","author":"TW Folescu","year":"2015","journal-title":"BMC Pulm Med"},{"key":"ref5","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1038\/nrmicro1085","article-title":"The multifarious, multireplicon <italic>Burkholderia cepacia<\/italic> complex","volume":"3","author":"E Mahenthiralingam","year":"2005","journal-title":"Nat Rev Microbiol"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"607575","DOI":"10.1155\/2011\/607575","article-title":"<italic>Burkholderia cepacia<\/italic> complex: emerging multihost pathogens equipped with a wide range of virulence factors and determinants","volume":"2011","author":"SA Sousa","year":"2011","journal-title":"Int J Microbiol"},{"key":"ref7","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1093\/jac\/dkf137","article-title":"Influence of taxonomic status on the <italic>in vitro<\/italic> antimicrobial susceptibility of the <italic>Burkholderia cepacia<\/italic> complex","volume":"50","author":"S Nzula","year":"2002","journal-title":"J Antimicrob Chemother"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1186\/1471-2180-9-200","article-title":"Assessment of three Resistance-Nodulation-Cell Division drug efflux transporters of <italic>Burkholderia cenocepacia<\/italic> in intrinsic antibiotic resistance","volume":"9","author":"S Buroni","year":"2009","journal-title":"BMC Microbiol"},{"key":"ref9","doi-asserted-by":"crossref","first-page":"815","DOI":"10.3389\/fmicb.2015.00815","article-title":"Efflux-mediated resistance to a benzothiadiazol derivative effective against <italic>Burkholderia cenocepacia<\/italic>","volume":"6","author":"VC Scoffone","year":"2015","journal-title":"Front Microbiol"},{"key":"ref10","doi-asserted-by":"crossref","first-page":"7424","DOI":"10.1128\/AAC.03800-14","article-title":"Differential roles of RND efflux pumps in antimicrobial drug resistance of sessile and planktonic <italic>Burkholderia cenocepacia<\/italic> cells","volume":"58","author":"S Buroni","year":"2014","journal-title":"Antimicrob Agents Chemother"},{"key":"ref11","first-page":"183","article-title":"<italic>Burkholderia<\/italic>: from genomes to function","author":"S Bazzini","year":"2014"},{"key":"ref12","doi-asserted-by":"crossref","first-page":"422","DOI":"10.1038\/8223","article-title":"Structure and mechanism of glutamate racemase from <italic>Aquifex pyrophilus<\/italic>","volume":"6","author":"KY Hwang","year":"1999","journal-title":"Nat Struct Biol"},{"key":"ref13","doi-asserted-by":"crossref","first-page":"817","DOI":"10.1038\/nature05689","article-title":"Exploitation of structural and regulatory diversity in glutamate racemases","volume":"447","author":"T Lundqvist","year":"2007","journal-title":"Nature"},{"key":"ref14","doi-asserted-by":"crossref","first-page":"620","DOI":"10.1128\/MMBR.00016-07","article-title":"Lipid intermediates in the biosynthesis of bacterial peptidoglycan","volume":"71","author":"J van Heijenoort","year":"2007","journal-title":"Microbiol Mol Biol Rev"},{"key":"ref15","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1039\/a804532a","article-title":"Recent advances in the formation of the bacterial peptidoglycan monomer unit","volume":"18","author":"J van Heijenoort","year":"2001","journal-title":"Nat Prod Rep"},{"key":"ref16","doi-asserted-by":"crossref","first-page":"6919","DOI":"10.1021\/cr2000702","article-title":"Drug discovery targeting amino acid racemases","volume":"111","author":"P Conti","year":"2011","journal-title":"Chem Rev"},{"key":"ref17","doi-asserted-by":"crossref","first-page":"930","DOI":"10.1016\/j.bmcl.2008.11.113","article-title":"Potent and selective inhibitors of <italic>Helicobacter pylori<\/italic> glutamate racemase (MurI): pyridodiazepine amines","volume":"19","author":"B Geng","year":"2009","journal-title":"Bioorg Med Chem Lett"},{"key":"ref18","doi-asserted-by":"crossref","first-page":"1707","DOI":"10.1016\/j.str.2005.07.024","article-title":"Substrate-induced conformational changes in <italic>Bacillus subtilis<\/italic> glutamate racemase and their implications for drug discovery","volume":"13","author":"SN Ruzheinikov","year":"2005","journal-title":"Structure"},{"key":"ref19","doi-asserted-by":"crossref","first-page":"434","DOI":"10.1016\/j.jmb.2007.05.003","article-title":"Structural basis for glutamate racemase inhibition","volume":"372","author":"KH Kim","year":"2007","journal-title":"J Mol Biol"},{"key":"ref20","doi-asserted-by":"crossref","first-page":"610","DOI":"10.1271\/bbb.59.610","article-title":"Cloning, purification, and properties of a cofactor-independent glutamate racemase from <italic>Lactobacillus brevis<\/italic> ATCC 8287","volume":"59","author":"M Yagasaki","year":"1995","journal-title":"Biosci Biotechnol Biochem"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"5265","DOI":"10.1128\/JB.00352-07","article-title":"Functional comparison of the two <italic>Bacillus anthracis<\/italic> glutamate racemases","volume":"189","author":"D Dodd","year":"2007","journal-title":"J Bacteriol"},{"key":"ref22","doi-asserted-by":"crossref","first-page":"6100","DOI":"10.1016\/j.bmcl.2008.10.022","article-title":"Exploring 8-benzyl pteridine-6,7-diones as inhibitors of glutamate racemase (MurI) in gram-positive bacteria","volume":"18","author":"GA Breault","year":"2008","journal-title":"Bioorg Med Chem Lett"},{"key":"ref23","doi-asserted-by":"crossref","first-page":"5274","DOI":"10.1021\/ja809660g","article-title":"Determinants of catalytic power and ligand binding in glutamate racemase","volume":"131","author":"MA Spies","year":"2009","journal-title":"J Am Chem Soc"},{"key":"ref24","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1002\/minf.201100014","article-title":"Hybrid steered molecular dynamics-docking: an efficient solution to the problem of ranking inhibitor affinities against a flexible drug target","volume":"30","author":"KL Whalen","year":"2011","journal-title":"Mol Inform"},{"key":"ref25","doi-asserted-by":"crossref","first-page":"3416","DOI":"10.1021\/jp201037t","article-title":"Nature of allosteric inhibition in glutamate racemase: discovery and characterization of a cryptic inhibitory pocket using atomistic MD simulations and pKa calculations","volume":"115","author":"KL Whalen","year":"2011","journal-title":"J Phys Chem B"},{"key":"ref26","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1021\/ml900005b","article-title":"Exploiting enzyme plasticity in virtual screening: high efficiency inhibitors of glutamate racemase","volume":"1","author":"KL Whalen","year":"2010","journal-title":"ACS Med Chem Lett"},{"key":"ref27","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1016\/j.cattod.2013.06.013","article-title":"Zinc(II)-1,3,5-triapentadienate complex as effective catalyst in Henry reaction","volume":"217","author":"NQ Shixaliyev","year":"2013","journal-title":"Catalysts today"},{"key":"ref28","doi-asserted-by":"crossref","first-page":"4807","DOI":"10.1039\/C4NJ00797B","article-title":"Halogen-bonded tris(2,4-bis(tricholoronethyl)-1,3,5-triazapentadienato)-M(III) [M = Mn, Fe, Co] complexes and their catalytic activity in the peroxidative oxidation of 1-phenylethanol to acetophenone","volume":"38","author":"NQ Shixaliyev","year":"2014","journal-title":"New J Chem"},{"key":"ref29","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1016\/j.pep.2012.11.012","article-title":"Recombinant expression, purification and characterisation of the native glutamate racemase from <italic>Lactobacillus plantarum<\/italic> NC8","volume":"88","author":"N B\u00f6hmer","year":"2013","journal-title":"Protein Expr Purif"},{"key":"ref30","author":"A Copeland","year":"2000"},{"key":"ref31","doi-asserted-by":"crossref","first-page":"D204","DOI":"10.1093\/nar\/gku989","article-title":"UniProt: a hub for protein information","volume":"43","author":"U Consortium","year":"2015","journal-title":"Nucleic Acids Res"},{"key":"ref32","doi-asserted-by":"crossref","first-page":"3389","DOI":"10.1093\/nar\/25.17.3389","article-title":"Gapped BLAST and PSI-BLAST: a new generation of protein database search programs","volume":"25","author":"SF Altschul","year":"1997","journal-title":"Nucleic Acids Res"},{"key":"ref33","doi-asserted-by":"crossref","first-page":"W244","DOI":"10.1093\/nar\/gki408","article-title":"The HHpred interactive server for protein homology detection and structure prediction","volume":"33","author":"J S\u00f6ding","year":"2005","journal-title":"Nucleic Acids Res"},{"key":"ref34","doi-asserted-by":"crossref","DOI":"10.1002\/0471250953.bi0506s15","article-title":"Comparative protein structure modeling using Modeller","author":"N Eswar","year":"2006","journal-title":"Curr Protoc Bioinformatics"},{"key":"ref35","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1093\/nar\/29.1.221","article-title":"PDBsum: summaries and analyses of PDB structures","volume":"29","author":"RA Laskowski","year":"2001","journal-title":"Nucleic Acids Res"},{"key":"ref36","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1186\/1472-6807-9-35","article-title":"QMEANclust: estimation of protein model quality by combining a composite scoring function with structural density information","volume":"9","author":"P Benkert","year":"2009","journal-title":"BMC Struct Biol"},{"key":"ref37","doi-asserted-by":"crossref","first-page":"10037","DOI":"10.1073\/pnas.181342398","article-title":"Electrostatics of nanosystems: application to microtubules and the ribosome","volume":"98","author":"NA Baker","year":"2001","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref38","unstructured":"Schrodinger, LLC. The PyMOL Molecular Graphics System, Version 1.3r1. 2010."},{"key":"ref39","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1016\/j.bioorg.2004.08.002","article-title":"Chemical cross-linking and protein-protein interactions-a review with illustrative protocols","volume":"32","author":"R Kluger","year":"2004","journal-title":"Bioorg Chem"},{"key":"ref40","author":"J Sambrook","year":"2001"},{"key":"ref41","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1093\/jac\/dkl231","article-title":"A new rapid and simple colorimetric method to detect pyrazinamide resistance in <italic>Mycobacterium tuberculosis<\/italic> using nicotinamide","volume":"58","author":"A Martin","year":"2006","journal-title":"J Antimicrob Chemother"},{"key":"ref42","doi-asserted-by":"crossref","first-page":"1219","DOI":"10.1016\/j.jmb.2007.05.093","article-title":"Structural and functional analysis of two glutamate racemase isozymes from <italic>Bacillus anthracis<\/italic> and implications for inhibitor design","volume":"371","author":"M May","year":"2007","journal-title":"J Mol Biol"},{"key":"ref43","doi-asserted-by":"crossref","first-page":"2031","DOI":"10.1107\/S0907444904021134","article-title":"Expression, purification and preliminary X-ray analysis of crystals of <italic>Bacillus subtilis<\/italic> glutamate racemase","volume":"60","author":"MA Taal","year":"2004","journal-title":"Acta Crystallogr D Biol Crystallogr"},{"key":"ref44","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1016\/j.abb.2009.09.009","article-title":"Kinetic characterization and quaternary structure of glutamate racemase from the periodontal anaerobe <italic>Fusobacterium nucleatum<\/italic>","volume":"491","author":"J Potrykus","year":"2009","journal-title":"Arch Biochem Biophys"},{"key":"ref45","doi-asserted-by":"crossref","first-page":"4559","DOI":"10.1021\/jm020901d","article-title":"4-Substituted D-glutamic acid analogues: the first potent inhibitors of glutamate racemase (MurI) enzyme with antibacterial activity","volume":"45","author":"A de Dios","year":"2002","journal-title":"J Med Chem"},{"key":"ref46","doi-asserted-by":"crossref","first-page":"1681","DOI":"10.1002\/cmdc.201390044","article-title":"<italic>In silico<\/italic> optimization of a fragment-based hit yields biologically active, high-efficiency inhibitors for glutamate racemase","volume":"8","author":"KL Whalen","year":"2013","journal-title":"ChemMedChem"},{"key":"ref47","doi-asserted-by":"crossref","first-page":"1567","DOI":"10.1021\/cb500149m","article-title":"Rv2466c mediates the activation of TP053 to kill replicating and non-replicating <italic>Mycobacterium tuberculosis<\/italic>","volume":"9","author":"D Albesa-Jov\u00e9","year":"2014","journal-title":"ACS Chem Biol"},{"key":"ref48","doi-asserted-by":"crossref","first-page":"705","DOI":"10.1021\/cb5007163","article-title":"2-Carboxyquinoxalines kill <italic>Mycobacterium tuberculosis<\/italic> through noncovalent inhibition of DprE1","volume":"10","author":"J Neres","year":"2015","journal-title":"ACS Chem Biol"},{"key":"ref49","doi-asserted-by":"crossref","first-page":"917","DOI":"10.1016\/j.chembiol.2015.05.016","article-title":"Thiophenecarboxamide derivatives activated by EthA kill <italic>Mycobacterium tuberculosis<\/italic> by inhibiting the CTP synthetase PyrG","volume":"22","author":"G Mori","year":"2015","journal-title":"Chem Biol"},{"issue":"Supplement","key":"ref50","doi-asserted-by":"crossref","first-page":"S27","DOI":"10.1016\/j.jbiotec.2015.06.072","article-title":"Antimicrobial activity of halogen\u2013Bonded bis-(2,4-bis (trichloromethyl)-1,3,5-triazapentadienato)\u2013Me (II) [Ni, Cu] complexes","volume":"208","author":"A Israyilova","year":"2015","journal-title":"J Biotechnol"},{"key":"ref51","doi-asserted-by":"crossref","first-page":"2415","DOI":"10.1128\/AAC.02438-13","article-title":"Mechanism of resistance to an antitubercular 2-thiopyridine derivative that is also active against <italic>Burkholderia cenocepacia<\/italic>","volume":"58","author":"VC Scoffone","year":"2014","journal-title":"Antimicrob Agents Chemother"},{"key":"ref52","doi-asserted-by":"crossref","first-page":"815","DOI":"10.3389\/fmicb.2015.00815","article-title":"Efflux-mediated resistance to a benzothiadiazol derivative effective against <italic>Burkholderia cenocepacia<\/italic>","volume":"6","author":"VC Scoffone","year":"2015","journal-title":"Front Microbiol"},{"key":"ref53","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1111\/j.1751-7915.2008.00031.x","article-title":"Glutamate racemase as a target for drug discovery","volume":"1","author":"SL Fisher","year":"2008","journal-title":"Microb Biotechnol"},{"key":"ref54","doi-asserted-by":"crossref","first-page":"7045","DOI":"10.1021\/bi9005072","article-title":"Glutamate racemase dimerization inhibits dynamic conformational flexibility and reduces catalytic rates","volume":"48","author":"S Mehboob","year":"2009","journal-title":"Biochemistry"},{"key":"ref55","doi-asserted-by":"crossref","first-page":"9","DOI":"10.3389\/fchem.2014.00009","article-title":"Allosteric modulation of protein oligomerization: an emerging approach to drug design","volume":"2","author":"R Gabizon","year":"2014","journal-title":"Front Chem"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pone.0167350","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,5,8]],"date-time":"2020-05-08T20:22:06Z","timestamp":1588969326000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0167350"}},"subtitle":[],"editor":[{"given":"Israel","family":"Silman","sequence":"first","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2016,11,29]]},"references-count":55,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2016,11,29]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0167350","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,11,29]]}}}