{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T18:28:19Z","timestamp":1790533699441,"version":"4.1.0"},"reference-count":47,"publisher":"American Chemical Society (ACS)","issue":"10","license":[{"start":{"date-parts":[[2015,7,28]],"date-time":"2015-07-28T00:00:00Z","timestamp":1438041600000},"content-version":"vor","delay-in-days":365,"URL":"https:\/\/pubs.acs.org\/page\/policy\/authorchoice_termsofuse.html"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["AI064184"],"award-info":[{"award-number":["AI064184"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["AI76322"],"award-info":[{"award-number":["AI76322"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["GM103655"],"award-info":[{"award-number":["GM103655"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["GM106112"],"award-info":[{"award-number":["GM106112"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000015","name":"U.S. Department of Energy","doi-asserted-by":"publisher","award":["NA"],"award-info":[{"award-number":["NA"]}],"id":[{"id":"10.13039\/100000015","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000183","name":"Army Research Office","doi-asserted-by":"publisher","award":["W911NF-12-1-0390"],"award-info":[{"award-number":["W911NF-12-1-0390"]}],"id":[{"id":"10.13039\/100000183","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000928","name":"Welch Foundation","doi-asserted-by":"publisher","award":["F-1155"],"award-info":[{"award-number":["F-1155"]}],"id":[{"id":"10.13039\/100000928","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2014,10,17]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The current pandemic El Tor biotype of O1 Vibrio cholerae is resistant to polymyxins, whereas the previous pandemic strain of the classical biotype is polymyxin sensitive. The almEFG operon found in El Tor V. cholerae confers &amp;gt;100-fold resistance to polymyxins through the glycylation of lipopolysaccharide. Here, we present the mechanistic determination of initial steps in the AlmEFG pathway. We verify that AlmF is an aminoacyl carrier protein and identify AlmE as the enzyme required to activate AlmF as a functional carrier protein. A combination of structural information and activity assays was used to identify a pair of active site residues that are important for mediating AlmE glycine specificity. Overall, the structure of AlmE in complex with its glycyl-adenylate intermediate reveals that AlmE is related to Gram-positive d-alanine\/d-alanyl carrier protein ligase, while the trio of proteins in the AlmEFG system forms a chemical pathway that resembles the division of labor in nonribosomal peptide synthetases.<\/jats:p>","DOI":"10.1021\/cb500438x","type":"journal-article","created":{"date-parts":[[2014,7,28]],"date-time":"2014-07-28T10:06:57Z","timestamp":1406542017000},"page":"2382-2392","source":"Crossref","is-referenced-by-count":58,"title":["Antimicrobial Peptide Resistance of\n                    <i>Vibrio cholerae<\/i>\n                    Results from an LPS Modification Pathway Related\nto Nonribosomal Peptide Synthetases"],"prefix":"10.1021","volume":"9","author":[{"given":"Jeremy C.","family":"Henderson","sequence":"first","affiliation":[{"name":"The University of Texas at Austin , , , , ,","place":["Austin, Texas, United States, 78712"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher D.","family":"Fage","sequence":"additional","affiliation":[{"name":"The University of Texas at Austin , , , , ,","place":["Austin, Texas, United States, 78712"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joe R.","family":"Cannon","sequence":"additional","affiliation":[{"name":"The University of Texas at Austin , , , , ,","place":["Austin, Texas, United States, 78712"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer S.","family":"Brodbelt","sequence":"additional","affiliation":[{"name":"The University of Texas at Austin , , , , ,","place":["Austin, Texas, United States, 78712"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adrian T.","family":"Keatinge-Clay","sequence":"additional","affiliation":[{"name":"The University of Texas at Austin , , , , ,","place":["Austin, Texas, United States, 78712"]},{"name":"The University of Texas at Austin , , , , ,","place":["Austin, Texas, United States, 78712"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. Stephen","family":"Trent","sequence":"additional","affiliation":[{"name":"The University of Texas at Austin , , , , ,","place":["Austin, Texas, United States, 78712"]},{"name":"The University of Texas at Austin , , , , ,","place":["Austin, Texas, United States, 78712"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2014,7,28]]},"reference":[{"key":"2026090203271920400_cit1","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1016\/S1473-3099(06)70580-1","article-title":"Colistin: the re-emerging antibiotic\nfor multidrug-resistant Gram-negative bacterial infections","volume":"6","author":"Li","year":"2006","journal-title":"Lancet Infect. Dis."},{"key":"2026090203271920400_cit2","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1016\/j.ijantimicag.2009.10.005","article-title":"Colistin therapy\nfor microbiologically documented multidrug-resistant Gram-negative\nbacterial infections: a retrospective cohort study of 258 patients","volume":"35","author":"Falagas","year":"2010","journal-title":"Int. J. Antimicrob. Agents"},{"key":"2026090203271920400_cit3","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3389\/fmicb.2013.00353","article-title":"Antibiotic development\nchallenges: the various mechanisms of action of antimicrobial peptides\nand of bacterial resistance","volume":"4","author":"Guilhelmelli","year":"2013","journal-title":"Front. Microbiol."},{"key":"2026090203271920400_cit4","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1016\/j.drup.2010.05.002","article-title":"Resistance\nto polymyxins: Mechanisms,\nfrequency and treatment options","volume":"13","author":"Falagas","year":"2010","journal-title":"Drug Resist.\nUpdates"},{"key":"2026090203271920400_cit5","doi-asserted-by":"crossref","first-page":"940","DOI":"10.1002\/iub.240","article-title":"Tuning the\nproperties of the bacterial membrane with aminoacylated phosphatidylglycerol","volume":"61","author":"Roy","year":"2009","journal-title":"IUBMB Life"},{"key":"2026090203271920400_cit6","doi-asserted-by":"crossref","first-page":"686","DOI":"10.1128\/MMBR.67.4.686-723.2003","article-title":"A continuum of anionic charge: structures and functions\nof D-alanyl-teichoic acids in gram-positive bacteria","volume":"67","author":"Neuhaus","year":"2003","journal-title":"Microbiol. Mol. Biol. Rev."},{"key":"2026090203271920400_cit7","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1038\/nrmicro3047","article-title":"Fortifying the barrier: the impact of lipid A remodelling\non bacterial pathogenesis","volume":"11","author":"Needham","year":"2013","journal-title":"Nat. Rev. Microbiol."},{"key":"2026090203271920400_cit8","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1146\/annurev.biochem.76.010307.145803","article-title":"Lipid A modification\nsystems in gram-negative bacteria","volume":"76","author":"Raetz","year":"2007","journal-title":"Annu. Rev.\nBiochem."},{"key":"2026090203271920400_cit9","doi-asserted-by":"crossref","first-page":"8722","DOI":"10.1073\/pnas.1201313109","article-title":"Amino acid\naddition to Vibrio cholerae LPS establishes a link between surface\nremodeling in gram-positive and gram-negative bacteria","volume":"109","author":"Hankins","year":"2012","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"2026090203271920400_cit10","first-page":"987","article-title":"Differentiation between vibrio cholerae\nand Vibrio cholerae biotype El Tor by the polymyxin B disc test: comparative\nresults with TCBS, Monsur\u2019s, Mueller-Hinton and nutrient agar\nmedia","volume":"36","author":"Gangarosa","year":"1967","journal-title":"Bull. W. H. O."},{"key":"2026090203271920400_cit11","doi-asserted-by":"crossref","first-page":"1313","DOI":"10.1111\/j.1365-2958.2011.07765.x","article-title":"Elucidation of a novel Vibrio cholerae\nlipid A secondary hydroxy-acyltransferase and its role in innate immune\nrecognition","volume":"81","author":"Hankins","year":"2011","journal-title":"Mol. Microbiol."},{"key":"2026090203271920400_cit12","doi-asserted-by":"crossref","first-page":"4488","DOI":"10.1128\/IAI.73.8.4488-4493.2005","article-title":"Transcriptional\nprofiling of Vibrio cholerae recovered directly from patient specimens\nduring early and late stages of human infection","volume":"73","author":"LaRocque","year":"2005","journal-title":"Infect. Immun."},{"key":"2026090203271920400_cit13","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1016\/j.chom.2011.07.007","article-title":"RNA-Seq-based monitoring of infection-linked changes\nin Vibrio cholerae gene expression","volume":"10","author":"Mandlik","year":"2011","journal-title":"Cell Host\nMicrobe"},{"key":"2026090203271920400_cit14","doi-asserted-by":"crossref","first-page":"1111","DOI":"10.1039\/c2np20062g","article-title":"The structural role\nof the carrier protein \u2013\nactive controller or passive carrier","volume":"29","author":"Crosby","year":"2012","journal-title":"Nat. Prod.\nRep."},{"key":"2026090203271920400_cit15","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1039\/C3NP70054B","article-title":"The phosphopantetheinyl\ntransferases: catalysis of a post-translational modification crucial\nfor life","volume":"31","author":"Beld","year":"2014","journal-title":"Nat. Prod. Rep."},{"key":"2026090203271920400_cit16","doi-asserted-by":"crossref","first-page":"1089","DOI":"10.1126\/science.1176667","article-title":"Antibiotics for emerging pathogens","volume":"325","author":"Fischbach","year":"2009","journal-title":"Science"},{"key":"2026090203271920400_cit17","doi-asserted-by":"crossref","first-page":"422","DOI":"10.1038\/nature12679","article-title":"Chasing acyl carrier protein through a catalytic cycle of lipid A\nproduction","volume":"505","author":"Masoudi","year":"2013","journal-title":"Nature"},{"key":"2026090203271920400_cit18","doi-asserted-by":"crossref","first-page":"17406","DOI":"10.1073\/pnas.1207028109","article-title":"Structure of the\nenzyme-acyl carrier protein (ACP) substrate gatekeeper complex required\nfor biotin synthesis","volume":"109","author":"Agarwal","year":"2012","journal-title":"Proc. Natl. Acad. Sci.\nU.S.A."},{"key":"2026090203271920400_cit19","doi-asserted-by":"crossref","first-page":"2669","DOI":"10.1016\/S0021-9258(19)69666-3","article-title":"Molecular\nproperties of acyl carrier\nprotein derivatives","volume":"256","author":"Rock","year":"1981","journal-title":"J. Biol. Chem."},{"key":"2026090203271920400_cit20","doi-asserted-by":"crossref","first-page":"5201","DOI":"10.1016\/S0021-9258(18)96417-3","article-title":"Acyl carrier protein\nVIII. Studies of acyl carrier\nprotein and coenzyme A in Escherichia coli pantothenate or \u0392-alanine\nauxotrophs","volume":"241","author":"Alberts","year":"1966","journal-title":"J. Biol. Chem."},{"key":"2026090203271920400_cit21","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1021\/bi061930j","article-title":"Characterization\nof the aminocarboxycyclopropane-forming\nenzyme CmaC","volume":"46","author":"Kelly","year":"2007","journal-title":"Biochemistry (Moscow)"},{"key":"2026090203271920400_cit22","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1016\/0003-2697(91)90194-X","article-title":"A malachite green colorimetric assay\nfor protein phosphatase activity","volume":"192","author":"Geladopoulos","year":"1991","journal-title":"Anal. Biochem."},{"key":"2026090203271920400_cit23","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1016\/j.jmb.2009.03.040","article-title":"Crystal structure of Bacillus cereus\nd-alanyl carrier protein ligase (DltA) in complex with ATP","volume":"388","author":"Osman","year":"2009","journal-title":"J. Mol. Biol."},{"key":"2026090203271920400_cit24","doi-asserted-by":"crossref","first-page":"3112","DOI":"10.1073\/pnas.97.7.3112","article-title":"Heterologous expression in Escherichia coli of the\nfirst module of the nonribosomal peptide synthetase for chloroeremomycin,\na vancomycin-type glycopeptide antibiotic","volume":"97","author":"Trauger","year":"2000","journal-title":"Proc.\nNatl. Acad. Sci. U.S.A."},{"key":"2026090203271920400_cit25","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1016\/j.ab.2008.12.014","article-title":"A nonradioactive high-throughput\nassay for screening and characterization of adenylation domains for\nnonribosomal peptide combinatorial biosynthesis","volume":"386","author":"McQuade","year":"2009","journal-title":"Anal. Biochem."},{"key":"2026090203271920400_cit26","doi-asserted-by":"crossref","first-page":"4174","DOI":"10.1093\/emboj\/16.14.4174","article-title":"Structural basis for\nthe activation of phenylalanine in the non-ribosomal biosynthesis\nof gramicidin S","volume":"16","author":"Conti","year":"1997","journal-title":"EMBO J."},{"key":"2026090203271920400_cit27","doi-asserted-by":"crossref","first-page":"1425","DOI":"10.1021\/bi035911a","article-title":"Crystal structure of yeast acetyl-coenzyme\nA synthetase in complex\nwith AMP","volume":"43","author":"Jogl","year":"2004","journal-title":"Biochemistry (Moscow)"},{"key":"2026090203271920400_cit28","doi-asserted-by":"crossref","first-page":"2866","DOI":"10.1021\/bi0271603","article-title":"The 1.75\n\u00c5 crystal structure of acetyl-CoA synthetase bound to adenosine-5\u2032-propylphosphate\nand coenzyme A","volume":"42","author":"Gulick","year":"2003","journal-title":"Biochemistry (Moscow)"},{"key":"2026090203271920400_cit29","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1016\/S0969-2126(96)00033-0","article-title":"Crystal structure\nof firefly luciferase\nthrows light on a superfamily of adenylate-forming enzymes","volume":"4","author":"Conti","year":"1996","journal-title":"Structure"},{"key":"2026090203271920400_cit30","doi-asserted-by":"crossref","first-page":"4115","DOI":"10.1021\/bi9002327","article-title":"The mechanism\nof domain alternation in the acyl-adenylate forming ligase superfamily\nmember 4-chlorobenzoate: coenzyme A ligase","volume":"48","author":"Wu","year":"2009","journal-title":"Biochemistry (Moscow)"},{"key":"2026090203271920400_cit31","doi-asserted-by":"crossref","first-page":"32484","DOI":"10.1074\/jbc.M800557200","article-title":"Crystal structure of DltA: implications for the reaction\nmechanism of non-ribosomal peptide synthetase adenylation domains","volume":"283","author":"Yonus","year":"2008","journal-title":"J. Biol. Chem."},{"key":"2026090203271920400_cit32","doi-asserted-by":"crossref","first-page":"11473","DOI":"10.1021\/bi801363b","article-title":"Crystal structure and enantiomer selection by d-alanyl carrier protein ligase DltA from Bacillus cereus","volume":"47","author":"Du","year":"2008","journal-title":"Biochemistry (Moscow)"},{"key":"2026090203271920400_cit33","doi-asserted-by":"crossref","first-page":"3389","DOI":"10.1093\/nar\/25.17.3389","article-title":"Gapped\nBLAST and PSI-BLAST: a new\ngeneration of protein database search programs","volume":"25","author":"Altschul","year":"1997","journal-title":"Nucleic Acids Res."},{"key":"2026090203271920400_cit34","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1016\/j.chembiol.2010.12.014","article-title":"Enzymatic extender unit generation for in vitro polyketide\nsynthase reactions: structural and func-tional showcasing of Streptomyces\ncoelicolor MatB","volume":"18","author":"Hughes","year":"2011","journal-title":"Chem. Biol."},{"key":"2026090203271920400_cit35","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1016\/j.chembiol.2011.11.013","article-title":"Structural and functional\ninvestigation of the intermolecular interaction between NRPS adenylation\nand carrier protein domains","volume":"19","author":"Sundlov","year":"2012","journal-title":"Chem. Biol."},{"key":"2026090203271920400_cit36","doi-asserted-by":"crossref","first-page":"1868","DOI":"10.1099\/mic.0.069898-0","article-title":"Revised mechanism\nof D-alanine incorporation\ninto cell wall polymers in Gram-positive bacteria","volume":"159","author":"Reichmann","year":"2013","journal-title":"Microbiology"},{"key":"2026090203271920400_cit37","doi-asserted-by":"crossref","first-page":"1985","DOI":"10.1038\/ismej.2013.90","article-title":"Comparative genomics of pathogenic lineages of Vibrio\nnigripulchritudo identifies virulence-associated traits","volume":"7","author":"Goudene\u0300ge","year":"2013","journal-title":"ISME J."},{"key":"2026090203271920400_cit38","doi-asserted-by":"crossref","first-page":"14704","DOI":"10.1021\/bi701229k","article-title":"Mass spectrometric\nanalysis of intact lipooligosaccharide: direct evidence for O-acetylated sialic acids and discovery of O-linked glycine expressed by Campylobacter jejuni","volume":"46","author":"Dzieciatkowska","year":"2007","journal-title":"Biochemistry (Moscow)"},{"key":"2026090203271920400_cit39","doi-asserted-by":"crossref","first-page":"1241","DOI":"10.1016\/j.carres.2011.04.030","article-title":"Detailed\nstructural features of lipopolysaccharide glycoforms in nontypeable\nHaemophilus influenzae strain 2019","volume":"346","author":"Engskog","year":"2011","journal-title":"Carbohydr.\nRes."},{"key":"2026090203271920400_cit40","doi-asserted-by":"crossref","first-page":"260","DOI":"10.1093\/glycob\/cwm140","article-title":"Full structural\ncharacterization of Shigella flexneri M90T serotype 5 wild-type R-LPS\nand its galU mutant: glycine residue location in the inner core of\nthe lipopolysaccharide","volume":"18","author":"Molinaro","year":"2007","journal-title":"Glycobiology"},{"key":"2026090203271920400_cit41","doi-asserted-by":"crossref","first-page":"e43","DOI":"10.1093\/nar\/gkm067","article-title":"Vectors for co-expression of an unrestricted\nnumber\nof proteins","volume":"35","author":"Scheich","year":"2007","journal-title":"Nucleic Acids Res."},{"key":"2026090203271920400_cit42","doi-asserted-by":"crossref","first-page":"12646","DOI":"10.1021\/ja4029654","article-title":"Complete protein\ncharacterization using top-down mass\nspectrometry and ultraviolet photodissociation","volume":"135","author":"Shaw","year":"2013","journal-title":"J. Am. Chem. Soc."},{"key":"2026090203271920400_cit43","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1016\/S0076-6879(97)76066-X","article-title":"Processing of X-ray diffraction data collected in oscillation mode","volume":"276","author":"Otwinowski","year":"1997","journal-title":"Methods Enzymol."},{"key":"2026090203271920400_cit44","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1107\/S0907444910045749","article-title":"Overview\nof the CCP 4 suite and current developments","volume":"67","author":"Winn","year":"2011","journal-title":"Acta Crystallogr., Sect. D"},{"key":"2026090203271920400_cit45","doi-asserted-by":"crossref","first-page":"1171","DOI":"10.1038\/nprot.2008.91","article-title":"Automated macromolecular\nmodel building for X-ray crystallography using ARP\/wARP version 7","volume":"3","author":"Langer","year":"2008","journal-title":"Nat. Protoc."},{"key":"2026090203271920400_cit46","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1107\/S0907444909052925","article-title":"PHENIX: a comprehensive\nPython-based system for macromolecular structure solution","volume":"66","author":"Adams","year":"2010","journal-title":"Acta Crystallogr., Sect. D"},{"key":"2026090203271920400_cit47","doi-asserted-by":"crossref","first-page":"2126","DOI":"10.1107\/S0907444904019158","article-title":"Coot: model-building tools for molecular\ngraphics","volume":"60","author":"Emsley","year":"2004","journal-title":"Acta Crystallogr., Sect. D"}],"container-title":["ACS Chemical Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pubs.acs.org\/doi\/pdf\/10.1021\/cb500438x","content-type":"application\/pdf","content-version":"vor","intended-application":"unspecified"},{"URL":"https:\/\/pubs.acs.org\/acbcct\/article-pdf\/9\/10\/2382\/15724642\/cb500438x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pubs.acs.org\/acbcct\/article-pdf\/9\/10\/2382\/15724642\/cb500438x.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T07:27:30Z","timestamp":1788334050000},"score":1,"resource":{"primary":{"URL":"https:\/\/pubs.acs.org\/acbcct\/article\/9\/10\/2382\/1479173\/Antimicrobial-Peptide-Resistance-of-Vibrio"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,7,28]]},"references-count":47,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2014,7,28]]},"published-print":{"date-parts":[[2014,10,17]]}},"URL":"https:\/\/doi.org\/10.1021\/cb500438x","relation":{},"ISSN":["1554-8929","1554-8937"],"issn-type":[{"value":"1554-8929","type":"print"},{"value":"1554-8937","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,7,28]]}}}