{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T11:02:31Z","timestamp":1789988551790,"version":"4.0.1"},"reference-count":39,"publisher":"American Chemical Society (ACS)","issue":"34","license":[{"start":{"date-parts":[[2020,8,18]],"date-time":"2020-08-18T00:00:00Z","timestamp":1597708800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/pubs.acs.org\/page\/policy\/authorchoice_ccby_termsofuse.html"}],"funder":[{"DOI":"10.13039\/501100004359","name":"Vetenskapsr?det","doi-asserted-by":"publisher","award":["2013-8804"],"award-info":[{"award-number":["2013-8804"]}],"id":[{"id":"10.13039\/501100004359","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,9,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Metallo-\u03b2-lactamase (MBL)-producing bacteria resistant to \u03b2-lactam antibiotics are a serious threat to human health. Despite great efforts and important progress in the discovery of MBL inhibitors (MBLIs), there is none in clinical use. Herein, inhibitor complexes of the MBL CcrA were investigated by NMR spectroscopy to provide perspectives on the further development of 2-(triazolylthio)acetamide-type MBLIs. By using the NMR-based chemical shift perturbation (CSP) and direction of CSP methodologies together with molecular docking, the spatial orientation of three compounds in the CcrA active site was investigated (4\u20136). Inhibitor 6 showed the best binding affinity (Kd \u2248 2.3 \u00b1 0.3 \u03bcM), followed by 4 (Kd = 11 \u00b1 11 \u03bcM) and 5 (Kd = 34 \u00b1 43 \u03bcM), as determined from the experimental NMR data. Based on the acquired knowledge, analogues of other MBLIs (1\u20133) were designed and evaluated in silico with the purpose of examining a strategy for promoting their interactions with the catalytic zinc ions.<\/jats:p>","DOI":"10.1021\/acsomega.0c02187","type":"journal-article","created":{"date-parts":[[2020,8,18]],"date-time":"2020-08-18T17:36:43Z","timestamp":1597772203000},"page":"21570-21578","source":"Crossref","is-referenced-by-count":5,"title":["Binding of 2-(Triazolylthio)acetamides to Metallo-\u03b2-lactamase\nCcrA Determined with NMR"],"prefix":"10.1021","volume":"5","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3798-3322","authenticated-orcid":true,"given":"Hanna","family":"Andersson","sequence":"first","affiliation":[{"name":"Uppsala University , , P.O. Box 576, ,","place":["Uppsala, Sweden, SE-751 23"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrik","family":"Jarvoll","sequence":"additional","affiliation":[{"name":"Centre for Antibiotic Resistance Research (CARe) at the University of Gothenburg , P.O. Box 440, ,","place":["Gothenburg, Sweden, SE-405 30"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shao-Kang","family":"Yang","sequence":"additional","affiliation":[{"name":"Northwest University , , ,","place":["Xi\u2019an, P. R. China, 710127"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2560-9659","authenticated-orcid":true,"given":"Ke-Wu","family":"Yang","sequence":"additional","affiliation":[{"name":"Northwest University , , ,","place":["Xi\u2019an, P. R. China, 710127"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0359-5970","authenticated-orcid":true,"given":"Ma\u0301te\u0301","family":"Erde\u0301lyi","sequence":"additional","affiliation":[{"name":"Uppsala University , , P.O. Box 576, ,","place":["Uppsala, Sweden, SE-751 23"]},{"name":"Centre for Antibiotic Resistance Research (CARe) at the University of Gothenburg , P.O. Box 440, ,","place":["Gothenburg, Sweden, SE-405 30"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2020,8,18]]},"reference":[{"key":"2026092106174032300_cit1","unstructured":"Antibacterial Agents in clinical\nDevelopment: An Analysis of the\nAntibacterial Clinical Development Pipeline, Including Tuberculosis; World Health Organization: Geneva, 2017."},{"key":"2026092106174032300_cit2","doi-asserted-by":"publisher","first-page":"490","DOI":"10.1093\/femsre\/fuz014","article-title":"Antibiotic resistance breakers: current\napproaches and future directions","volume":"43","author":"Laws","year":"2019","journal-title":"FEMS Microbiol.\nRev."},{"key":"2026092106174032300_cit3","doi-asserted-by":"publisher","first-page":"3472","DOI":"10.1016\/j.jmb.2019.04.002","article-title":"\u03b2-Lactamases and \u03b2-Lactamase\nInhibitors in the 21st Century","volume":"431","author":"Tooke","year":"2019","journal-title":"J. Mol. Biol."},{"key":"2026092106174032300_cit4","doi-asserted-by":"publisher","first-page":"321","DOI":"10.1098\/rstb.1980.0049","article-title":"The structure\nof beta-lactamases","volume":"289","author":"Ambler","year":"1980","journal-title":"Philos. Trans. R. Soc. London,\nSer. B"},{"key":"2026092106174032300_cit5","doi-asserted-by":"publisher","first-page":"969","DOI":"10.1128\/aac.01009-09","article-title":"Updated Functional\nClassification of \u03b2-Lactamases","volume":"54","author":"Bush","year":"2010","journal-title":"Antimicrob.\nAgents Chemother."},{"key":"2026092106174032300_cit6","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1016\/j.drup.2017.11.002","article-title":"An update on \u03b2-lactamase\ninhibitor discovery\nand development","volume":"36","author":"Docquier","year":"2018","journal-title":"Drug Resist. Updates"},{"key":"2026092106174032300_cit7","doi-asserted-by":"publisher","first-page":"593","DOI":"10.1128\/cmr.00008-07","article-title":"Bacteroides:\nthe Good, the Bad, and the Nitty-Gritty","volume":"20","author":"Wexler","year":"2007","journal-title":"Clin.\nMicrobiol. Rev."},{"key":"2026092106174032300_cit8","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.clinmicnews.2018.12.003","article-title":"Antimicrobial\nResistance in Clinically Important Anaerobes","volume":"41","author":"Pence","year":"2019","journal-title":"Clin. Microbiol. Newsl."},{"key":"2026092106174032300_cit9","doi-asserted-by":"publisher","first-page":"1590","DOI":"10.1128\/aac.34.8.1590","article-title":"Cloning\nand sequencing of the class\nB beta-lactamase gene (ccrA) from Bacteroides fragilis TAL3636","volume":"34","author":"Rasmussen","year":"1990","journal-title":"Antimicrob. 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Chem. Lett."},{"key":"2026092106174032300_cit16","doi-asserted-by":"publisher","first-page":"1014","DOI":"10.1021\/acsomega.7b01212","article-title":"Effect of Dimethyl Sulfoxide on the\nBinding of 1-Adamantane Carboxylic Acid to \u03b2- and \u03b3-Cyclodextrins","volume":"3","author":"Senac","year":"2018","journal-title":"ACS Omega"},{"key":"2026092106174032300_cit17","doi-asserted-by":"publisher","first-page":"326","DOI":"10.1002\/cphc.201800626","article-title":"Minute Additions of\nDMSO Affect Protein Dynamics Measurements by\nNMR Relaxation Experiments through Significant Changes in Solvent\nViscosity","volume":"20","author":"Wallerstein","year":"2019","journal-title":"ChemPhysChem"},{"key":"2026092106174032300_cit18","doi-asserted-by":"publisher","first-page":"2741","DOI":"10.1016\/s0960-894x(99)00458-8","article-title":"Structure-activity\nrelationships of biphenyl tetrazoles as metallo-\u03b2-lactamase\ninhibitors","volume":"9","author":"Toney","year":"1999","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"2026092106174032300_cit20","doi-asserted-by":"publisher","first-page":"413","DOI":"10.1021\/acsmedchemlett.5b00495","article-title":"Triazolylthioacetamide:\nA Valid Scaffold for the Development of New Delhi Metallo-\u03b2-Lactmase-1\n(NDM-1) Inhibitors","volume":"7","author":"Zhai","year":"2016","journal-title":"ACS Med. Chem. Lett."},{"key":"2026092106174032300_cit21","doi-asserted-by":"publisher","first-page":"5225","DOI":"10.1016\/j.bmcl.2017.10.038","article-title":"Azolylthioacetamides\nas a potent scaffold for the development of metallo-\u03b2-lactamase\ninhibitors","volume":"27","author":"Xiang","year":"2017","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"2026092106174032300_cit22","doi-asserted-by":"publisher","first-page":"1174","DOI":"10.3390\/molecules24061174","article-title":"Halogen-Substituted\nTriazolethioacetamides as a Potent Skeleton for\nthe Development of Metallo-\u03b2-Lactamase Inhibitors","volume":"24","author":"Zhang","year":"2019","journal-title":"Molecules"},{"key":"2026092106174032300_cit23","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.pnmrs.2013.02.001","article-title":"Using chemical\nshift perturbation to characterise ligand binding","volume":"73","author":"Williamson","year":"2013","journal-title":"Prog. Nucl. Magn. Reson. Spectrosc."},{"key":"2026092106174032300_cit24","doi-asserted-by":"publisher","first-page":"1407","DOI":"10.1021\/acsinfecdis.8b00137","article-title":"Synthesis\nand Preclinical Evaluation of TPA-Based Zinc Chelators as Metallo-\u03b2-lactamase\nInhibitors","volume":"4","author":"Schnaars","year":"2018","journal-title":"ACS Infect. Dis."},{"key":"2026092106174032300_cit25","doi-asserted-by":"publisher","first-page":"12126","DOI":"10.1021\/bi960976h","article-title":"Characterization\nof the Metal-Binding Sites of the \u03b2-Lactamase from Bacteroides\nfragilis","volume":"35","author":"Crowder","year":"1996","journal-title":"Biochemistry"},{"key":"2026092106174032300_cit26","doi-asserted-by":"publisher","first-page":"813","DOI":"10.1107\/s2053230x16016113","article-title":"The structure\nof the metallo-\u03b2-lactamase VIM-2 in complex with a triazolylthioacetamide\ninhibitor","volume":"72","author":"Christopeit","year":"2016","journal-title":"Acta Crystallogr., Sect. F: Struct.\nBiol. Commun."},{"key":"2026092106174032300_cit27","doi-asserted-by":"publisher","first-page":"14507","DOI":"10.1021\/bi990986t","article-title":"NMR Characterization\nof the Metallo-\u03b2-lactamase\nfrom Bacteroides fragilis and Its Interaction with a Tight-Binding\nInhibitor: Role of an Active-Site Loop","volume":"38","author":"Scrofani","year":"1999","journal-title":"Biochemistry"},{"key":"2026092106174032300_cit28","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1111\/j.1749-6632.2012.06796.x","article-title":"Metallo-\u03b2-lactamase\nstructure and function","volume":"1277","author":"Palzkill","year":"2013","journal-title":"Ann. N.Y. Acad. Sci."},{"key":"2026092106174032300_cit29","doi-asserted-by":"publisher","first-page":"660","DOI":"10.1128\/aac.45.3.660-663.2001","article-title":"Standard\nNumbering Scheme for Class B \u03b2-Lactamases","volume":"45","author":"Galleni","year":"2001","journal-title":"Antimicrob. Agents Chemother."},{"key":"2026092106174032300_cit30","doi-asserted-by":"publisher","first-page":"958","DOI":"10.1021\/ci800004w","article-title":"MM-GB\/SA Rescoring\nof Docking Poses in Structure-Based\nLead Optimization","volume":"48","author":"Guimara\u0303es","year":"2008","journal-title":"J. Chem. Inf. Model."},{"key":"2026092106174032300_cit31","doi-asserted-by":"publisher","first-page":"337","DOI":"10.1021\/jm030331x","article-title":"Structural Interaction Fingerprint\n(SIFt): A Novel Method for Analyzing Three-Dimensional Protein\u2013Ligand\nBinding Interactions","volume":"47","author":"Deng","year":"2004","journal-title":"J. Med. Chem."},{"key":"2026092106174032300_cit32","doi-asserted-by":"publisher","first-page":"4111","DOI":"10.1021\/jm500010b","article-title":"3-Substituted-N-(4-Hydroxynaphthalen-1-yl)arylsulfonamides\nas a Novel Class of Selective Mcl-1 Inhibitors: Structure-Based Design,\nSynthesis, SAR, and Biological Evaluation","volume":"57","author":"Abulwerdi","year":"2014","journal-title":"J.\nMed. Chem."},{"key":"2026092106174032300_cit33","doi-asserted-by":"publisher","first-page":"16038","DOI":"10.1021\/ja8062088","article-title":"Analysis\nof Chemical Shift Changes\nReveals the Binding Modes of Isoindolinone Inhibitors of the MDM2-p53\nInteraction","volume":"130","author":"Riedinger","year":"2008","journal-title":"J. Am. Chem. Soc."},{"key":"2026092106174032300_cit35","doi-asserted-by":"publisher","first-page":"10466","DOI":"10.1021\/acsomega.0c00590","article-title":"NMR Characterization\nof the Influence of Zinc(II) Ions on the Structural and Dynamic Behavior\nof the New Delhi Metallo-\u03b2-Lactamase-1 and on the Binding with\nFlavonols as Inhibitors","volume":"5","author":"Rivie\u0300re","year":"2020","journal-title":"ACS Omega"},{"key":"2026092106174032300_cit36","doi-asserted-by":"publisher","first-page":"150","DOI":"10.3389\/fchem.2018.00150","article-title":"Automated Fragmentation\nQM\/MM Calculation\nof NMR Chemical Shifts for Protein-Ligand Complexes","volume":"6","author":"Jin","year":"2018","journal-title":"Front. Chem."},{"key":"2026092106174032300_cit37","doi-asserted-by":"publisher","first-page":"39","DOI":"10.2174\/1568026033392705","article-title":"NMR Methods\nfor the Determination of Protein- Ligand Dissociation Constants","volume":"3","author":"Fielding","year":"2003","journal-title":"Curr. Top. Med. Chem."},{"key":"2026092106174032300_cit38","doi-asserted-by":"publisher","first-page":"436","DOI":"10.1002\/pro.3105","article-title":"(S)Pinning\ndown protein interactions by NMR","volume":"26","author":"Teilum","year":"2017","journal-title":"Protein Sci."},{"key":"2026092106174032300_cit39","doi-asserted-by":"publisher","first-page":"82","DOI":"10.1002\/jcb.10068","article-title":"Incorporating target heterogeneity in drug design","volume":"84","author":"Velazquez-Campoy","year":"2001","journal-title":"J. Cell. Biochem."},{"key":"2026092106174032300_cit40","doi-asserted-by":"publisher","first-page":"2819","DOI":"10.2174\/0929867322666150619104007","article-title":"Heterocyclic N-Oxides\n- An Emerging Class of Therapeutic\nAgents","volume":"22","author":"Mfuh","year":"2015","journal-title":"Curr. Med. Chem."},{"key":"2026092106174032300_cit41","doi-asserted-by":"publisher","first-page":"1142","DOI":"10.1111\/php.13100","article-title":"Optical Characterization\nof Zinc Pyrithione","volume":"95","author":"Sandiford","year":"2019","journal-title":"Photochem. Photobiol."}],"container-title":["ACS Omega"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pubs.acs.org\/doi\/pdf\/10.1021\/acsomega.0c02187","content-type":"application\/pdf","content-version":"vor","intended-application":"unspecified"},{"URL":"https:\/\/pubs.acs.org\/acsodf\/article-pdf\/5\/34\/21570\/67719709\/acsomega.0c02187.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pubs.acs.org\/acsodf\/article-pdf\/5\/34\/21570\/67719709\/acsomega.0c02187.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T10:32:28Z","timestamp":1789986748000},"score":1,"resource":{"primary":{"URL":"https:\/\/pubs.acs.org\/acsodf\/article\/5\/34\/21570\/583874\/Binding-of-2-Triazolylthio-acetamides-to-Metallo"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,8,18]]},"references-count":39,"journal-issue":{"issue":"34","published-online":{"date-parts":[[2020,8,18]]},"published-print":{"date-parts":[[2020,9,1]]}},"URL":"https:\/\/doi.org\/10.1021\/acsomega.0c02187","relation":{},"ISSN":["2470-1343"],"issn-type":[{"value":"2470-1343","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,8,18]]}}}