{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T14:09:19Z","timestamp":1789135759525,"version":"build-2803163510"},"reference-count":149,"publisher":"American Chemical Society (ACS)","issue":"9","license":[{"start":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T00:00:00Z","timestamp":1787702400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T00:00:00Z","timestamp":1787702400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T00:00:00Z","timestamp":1787702400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-045"}],"funder":[{"DOI":"10.13039\/100006206","name":"Biological and Environmental Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006206","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["1R01AI155723"],"award-info":[{"award-number":["1R01AI155723"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["P30GM133894"],"award-info":[{"award-number":["P30GM133894"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,9,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The \u03b2-lactam class of antibiotics remains indispensable for treating bacterial infections, yet their effectiveness is increasingly compromised by the emergence of carbapenem-hydrolyzing class D \u03b2-lactamases, the principal mechanism of carbapenem resistance in Acinetobacter baumannii and an important contributor to resistance in Enterobacterales. This review focuses on the structural biology and enzymatic mechanisms of these enzymes, with particular emphasis on the post-translationally carboxylated Lys73 and the solvent-restricted pocket that encloses this residue. This pocket maintains the lysine in its catalytically essential carboxylated state, enabling it to function as the general base during both acylation and deacylation. A unique gating mechanism enables the entry of a deacylating water into the catalytic lysine pocket via the opening of a hydrophobic cap induced by the 6\u03b1-hydroxyethyl group of the carbapenem following acylation of the enzyme. These insights provide a mechanistic framework for the development of next-generation therapeutics capable of overcoming carbapenem resistance. Recently designed carbapenem derivatives perturb carboxylation of the catalytic lysine or disrupt proper positioning of the catalytic water in the active site, which severely impairs deacylation and results in potent inhibition of CHDLs.<\/jats:p>","DOI":"10.1021\/acsinfecdis.6c00611","type":"journal-article","created":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T11:50:05Z","timestamp":1788263405000},"page":"2965-2984","source":"Crossref","is-referenced-by-count":0,"title":["Molecular Architecture\nand Catalytic Mechanisms of\nClass D Carbapenemases: Insights into Antibiotic Resistance and Carbapenem\nDesign"],"prefix":"10.1021","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1885-1511","authenticated-orcid":true,"given":"Clyde A.","family":"Smith","sequence":"first","affiliation":[{"name":"SLAC National Accelerator Laboratory , , , ,","place":["Menlo Park, California, United States, 94025"]},{"name":"Stanford University , , , ,","place":["Stanford, California, United States, 94303"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Toth","sequence":"additional","affiliation":[{"name":"University of Notre Dame , , , ,","place":["Notre Dame, Indiana, United States, 46556"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nichole K.","family":"Stewart","sequence":"additional","affiliation":[{"name":"University of Notre Dame , , , ,","place":["Notre Dame, Indiana, United States, 46556"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5327-8124","authenticated-orcid":true,"given":"Sergei B.","family":"Vakulenko","sequence":"additional","affiliation":[{"name":"University of Notre Dame , , , ,","place":["Notre Dame, Indiana, United States, 46556"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,8,26]]},"reference":[{"key":"2026091109101163100_cit1","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1515\/9781400874910-012","volume-title":"The Chemistry of Penicillin","author":"Crowfoot","year":"1949"},{"key":"2026091109101163100_cit2","doi-asserted-by":"publisher","first-page":"a025247","DOI":"10.1101\/cshperspect.a025247","article-title":"\u03b2-lactams\nand \u03b2-lactamase inhibitors: An\noverview","volume":"6","author":"Bush","year":"2016","journal-title":"Cold Spring Harbor Perspect. Med."},{"key":"2026091109101163100_cit3","doi-asserted-by":"publisher","first-page":"1623","DOI":"10.1039\/D1MD00200G","article-title":"\u03b2-Lactam antibiotic\ntargets and resistance mechanisms:\nfrom covalent inhibitors to substrates","volume":"12","author":"Mora-Ochomogo","year":"2021","journal-title":"RSC\nMed. Chem."},{"key":"2026091109101163100_cit4","doi-asserted-by":"publisher","first-page":"1300","DOI":"10.1016\/j.cell.2014.11.017","article-title":"Beta-lactam\nantibiotics induce a\nlethal malfunctioning of the bacterial cell wall synthesis machinery","volume":"159","author":"Cho","year":"2014","journal-title":"Cell"},{"key":"2026091109101163100_cit5","doi-asserted-by":"publisher","first-page":"112829","DOI":"10.1016\/j.ejmech.2020.112829","article-title":"\u03b2-lactam antibiotics:\nAn overview from a medicinal chemistry perspective","volume":"208","author":"Lima","year":"2020","journal-title":"Eur. J. Med. Chem."},{"key":"2026091109101163100_cit6","doi-asserted-by":"publisher","first-page":"440","DOI":"10.1128\/CMR.00001-07","article-title":"Carbapenemases: The versatile \u03b2-lactamases","volume":"20","author":"Queenan","year":"2007","journal-title":"Clin. Microbiol. Rev."},{"key":"2026091109101163100_cit7","doi-asserted-by":"publisher","first-page":"413","DOI":"10.3390\/antibiotics15040413","article-title":"Clinically significant carbapenemases in gram-negative\npathogens: Molecular diversity and advances in \u03b2-lactamase inhibitor\ntherapy","volume":"15","author":"Grossman","year":"2026","journal-title":"Antibiotics"},{"key":"2026091109101163100_cit8","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1038\/nchembio.1950","article-title":"Class D\n\u03b2-lactamases do exist\nin Gram-positive bacteria","volume":"12","author":"Toth","year":"2016","journal-title":"Nat. Chem. Biol."},{"key":"2026091109101163100_cit9","doi-asserted-by":"publisher","first-page":"917","DOI":"10.1080\/14756366.2017.1344235","article-title":"Beta-Lactamase DataBase\n(BLDB) - Structure and Function","volume":"32","author":"Naas","year":"2017","journal-title":"J. Enzyme Inhib.\nMed. Chem."},{"key":"2026091109101163100_cit10","doi-asserted-by":"publisher","first-page":"1","DOI":"10.7164\/antibiotics.32.1","article-title":"Thienamycin,\na new \u03b2-lactam antibiotic. I. Discovery, taxonomy, isolation\nand physical properties","volume":"32","author":"Kahan","year":"1979","journal-title":"J. Antibiot."},{"key":"2026091109101163100_cit11","doi-asserted-by":"publisher","first-page":"563","DOI":"10.1128\/AAC.41.3.563","article-title":"Imipenem resistance\nin Klebsiella pneumoniae is\nassociated with the combination of ACT-1, a plasmid-mediated AmpC\n\u03b2-lactamase, and the loss of an outer membrane protein","volume":"41","author":"Bradford","year":"1997","journal-title":"Antimicrob. Agents Chemother."},{"key":"2026091109101163100_cit12","doi-asserted-by":"publisher","first-page":"907","DOI":"10.1111\/j.1365-2958.2006.05146.x","article-title":"Structural\nbasis for the extended\nsubstrate spectrum of CMY-10, a plasmid-encoded class C \u03b2-lactamase","volume":"60","author":"Kim","year":"2006","journal-title":"Mol. Microbiol."},{"key":"2026091109101163100_cit13","doi-asserted-by":"publisher","first-page":"201","DOI":"10.1016\/j.ijantimicag.2006.09.006","article-title":"Reduced imipenem susceptibility\nin Klebsiella pneumoniae clinical isolates with plasmid-mediated\nCMY-2 and DHA-1 \u03b2-lactamases co-mediated by porin loss","volume":"29","author":"Lee","year":"2007","journal-title":"Int. J. Antimicrob. Agents"},{"key":"2026091109101163100_cit14","doi-asserted-by":"publisher","first-page":"4556","DOI":"10.1128\/AAC.01762-09","article-title":"Phenotypic and biochemical\ncomparison of the carbapenem-hydrolyzing activities of five plasmid-borne\nAmpC \u03b2-lactamases","volume":"54","author":"Mammeri","year":"2010","journal-title":"Antimicrob. Agents\nChemother."},{"key":"2026091109101163100_cit15","doi-asserted-by":"publisher","DOI":"10.1128\/mbio.00185-25","article-title":"Evolution\nof carbapenemase activity in the class C \u03b2-lactamase ADC-1","volume":"16","author":"Stewart","year":"2025","journal-title":"mBio"},{"key":"2026091109101163100_cit16","doi-asserted-by":"publisher","first-page":"826","DOI":"10.1111\/j.1469-0691.2006.01456.x","article-title":"Carbapenem resistance\nin Acinetobacter baumannii: Mechanisms and epidemiology","volume":"12","author":"Poirel","year":"2006","journal-title":"Clin. Microbiol.\nInfect."},{"key":"2026091109101163100_cit17","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1128\/jb.117.1.56-62.1974","article-title":"Molecular specificities\nof R factor-determined \u03b2-lactamases: Correlation with plasmid\ncompatibility","volume":"117","author":"Hedges","year":"1974","journal-title":"J. Bacteriol."},{"key":"2026091109101163100_cit18","doi-asserted-by":"publisher","first-page":"115","DOI":"10.1093\/jac\/2.2.115","article-title":"The \u03b2-lactamases\nof gram-negative bacteria and\ntheir role in resistance to \u03b2-lactam antibiotics","volume":"2","author":"Sykes","year":"1976","journal-title":"J. Antimicrob. Chemother."},{"key":"2026091109101163100_cit19","doi-asserted-by":"publisher","first-page":"715","DOI":"10.1128\/AAC.27.5.715","article-title":"Five novel plasmid-determined \u03b2-lactamases","volume":"27","author":"Medeiros","year":"1985","journal-title":"Antimicrob. Agents Chemother."},{"key":"2026091109101163100_cit20","doi-asserted-by":"publisher","first-page":"7378","DOI":"10.1073\/pnas.84.21.7378","article-title":"Precise insertion of antibiotic resistance\ndeterminants into Tn21-like transposons: Nucleotide sequence of the\nOXA-1 \u03b2-lactamase gene","volume":"84","author":"Ouellette","year":"1987","journal-title":"Proc. Natl. Acad.\nSci. U. S. A."},{"key":"2026091109101163100_cit21","doi-asserted-by":"publisher","first-page":"241","DOI":"10.1128\/CMR.00117-13","article-title":"OXA \u03b2-lactamases","volume":"27","author":"Evans","year":"2014","journal-title":"Clin.\nMicrobiol. Rev."},{"key":"2026091109101163100_cit22","doi-asserted-by":"publisher","first-page":"398","DOI":"10.3390\/antibiotics3030398","article-title":"Acquired class D \u03b2-lactamases","volume":"3","author":"Antunes","year":"2014","journal-title":"Antibiotics"},{"issue":"2","key":"2026091109101163100_cit23","doi-asserted-by":"publisher","first-page":"81","DOI":"10.1016\/0924-8579(93)90045-7","article-title":"ARI 1: \u03b2-lactamase-mediated\nimipenem resistance\nin Acinetobacter baumannii","volume":"2","author":"Paton","year":"1993","journal-title":"Int. J. Antimicrob. Agents"},{"key":"2026091109101163100_cit24","doi-asserted-by":"publisher","first-page":"585","DOI":"10.1093\/jac\/36.3.585","article-title":"Transferable\nimipenem-resistance\nin Acinetobacter species from a clinical source","volume":"36","author":"Scaife","year":"1995","journal-title":"J. Antimicrob. Chemother."},{"key":"2026091109101163100_cit25","doi-asserted-by":"publisher","first-page":"1556","DOI":"10.1128\/AAC.44.6.1556-1561.2000","article-title":"OXA-24, a\nnovel class D \u03b2-lactamase\nwith carbapenemase activity in an Acinetobacter baumannii clinical strain","volume":"44","author":"Bou","year":"2000","journal-title":"Antimicrob. Agents Chemother."},{"key":"2026091109101163100_cit26","doi-asserted-by":"publisher","first-page":"268","DOI":"10.1128\/AAC.47.1.268-273.2003","article-title":"Genetic and functional\nanalysis of the chromosome-encoded carbapenem-hydrolyzing oxacillinase\nOXA-40 of Acinetobacter baumannii","volume":"47","author":"Heritier","year":"2003","journal-title":"Antimicrob. Agents Chemother."},{"issue":"6","key":"2026091109101163100_cit27","doi-asserted-by":"publisher","first-page":"2268","DOI":"10.1128\/AAC.00166-06","article-title":"First report\nof the carbapenem-hydrolyzing oxacillinase\nOXA-58 in Acinetobacter baumannii isolates in Italy","volume":"50","author":"Bertini","year":"2006","journal-title":"Antimicrob. Agents Chemother."},{"key":"2026091109101163100_cit28","doi-asserted-by":"publisher","first-page":"5372","DOI":"10.1128\/AAC.00629-10","article-title":"OXA-134, a naturally occurring carbapenem-hydrolyzing\nclass D \u03b2-lactamase from Acinetobacter lwoffii","volume":"54","author":"Figueiredo","year":"2010","journal-title":"Antimicrob. Agents Chemother."},{"key":"2026091109101163100_cit29","doi-asserted-by":"publisher","first-page":"5035","DOI":"10.1128\/AAC.00856-09","article-title":"OXA-143, a\nnovel carbapenem-hydrolyzing class D \u03b2-lactamase in Acinetobacter baumannii","volume":"53","author":"Higgins","year":"2009","journal-title":"Antimicrob.\nAgents Chemother."},{"key":"2026091109101163100_cit30","doi-asserted-by":"publisher","first-page":"907","DOI":"10.1111\/j.1469-0691.2011.03708.x","article-title":"Identification of the naturally occurring genes encoding\ncarbapenem-hydrolysing oxacillinases from Acinetobacter haemolyticus Acinetobacter Johnsonii, And Acinetobacter Calcoaceticus","volume":"18","author":"Figueiredo","year":"2012","journal-title":"Clin. Microbiol. Infect."},{"key":"2026091109101163100_cit31","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1111\/j.1469-0691.2004.01016.x","article-title":"Characterisation\nof OXA-51, a novel\nclass D carbapenemase found in genetically unrelated clinical strains\nof Acinetobacter baumannii from Argentina","volume":"11","author":"Brown","year":"2005","journal-title":"Clin. Microbiol. Infect."},{"key":"2026091109101163100_cit32","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1128\/AAC.48.1.15-22.2004","article-title":"Emergence of oxacillinase-mediated\nresistance to imipenem in Klebsiella pneumoniae","volume":"48","author":"Poirel","year":"2004","journal-title":"Antimicrob. Agents Chemother."},{"key":"2026091109101163100_cit33","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1128\/mBio.01803-18","article-title":"Intrinsic\nclass D \u03b2-lactamases of Clostridium difficile","volume":"9","author":"Toth","year":"2018","journal-title":"mBio"},{"issue":"3","key":"2026091109101163100_cit34","doi-asserted-by":"publisher","first-page":"1073913","DOI":"10.1016\/j.jsb.2019.09.008","article-title":"The crystal\nstructures of CDD-1, the intrinsic class D \u03b2-lactamase from\nthe pathogenic Gram-positive bacterium Clostridioides difficile, and its complex with cefotaxime","volume":"208","author":"Stewart","year":"2019","journal-title":"J. Struct.\nBiol."},{"key":"2026091109101163100_cit35","doi-asserted-by":"publisher","first-page":"1765","DOI":"10.1021\/acsinfecdis.1c00094","article-title":"In Crystallo time-resolved\ninteraction\nof the Clostridioides difficile CDD-1 enzyme with\navibactam provides new insights into the catalytic mechanism of class\nD \u03b2-lactamases","volume":"7","author":"Stewart","year":"2021","journal-title":"ACS Infect. Dis."},{"key":"2026091109101163100_cit36","doi-asserted-by":"publisher","first-page":"720","DOI":"10.3390\/biom10050720","article-title":"Carbapenemases:\ntransforming Acinetobacter baumannii into a yet more\ndangerous menace","volume":"10","author":"Ramirez","year":"2020","journal-title":"Biomolecules"},{"key":"2026091109101163100_cit37","doi-asserted-by":"publisher","first-page":"35","DOI":"10.3201\/eid1601.090852","article-title":"Worldwide dissemination\nof the blaOXA-23 carbapenemase gene of Acinetobacter baumannii","volume":"16","author":"Mugnier","year":"2009","journal-title":"Emerg. Infect. Dis."},{"key":"2026091109101163100_cit38","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1128\/AAC.01512-08","article-title":"Diversity,\nepidemiology, and genetics\nof class D \u03b2-lactamases","volume":"54","author":"Poirel","year":"2010","journal-title":"Antimicrob. Agents\nChemother."},{"key":"2026091109101163100_cit39","doi-asserted-by":"publisher","first-page":"2749","DOI":"10.1093\/jac\/dkv181","article-title":"OXA-372,\na novel carbapenem-hydrolysing class D \u03b2-lactamase from a Citrobacter freundii isolated from a hospital wastewater\nplant","volume":"70","author":"Antonelli","year":"2015","journal-title":"J. Antimicrob. Chemother."},{"key":"2026091109101163100_cit40","doi-asserted-by":"publisher","first-page":"2469","DOI":"10.1093\/jac\/dkx184","article-title":"OXA-427, a\nnew plasmid-borne carbapenem-hydrolysing class D \u03b2-lactamase\nin Enterobacteriaceae","volume":"72","author":"Bogaerts","year":"2017","journal-title":"J. Antimicrob.\nChemother."},{"key":"2026091109101163100_cit41","doi-asserted-by":"publisher","DOI":"10.1128\/mSphere.00593-21","article-title":"Genetic Environment\nSurrounding blaOXA-55-like in Clinical Isolates of Shewanella algae Clade and Enhanced Expression of blaOXA-55-like in a Carbapenem-Resistant Isolate","volume":"6","author":"Ohama","year":"2021","journal-title":"mSphere"},{"key":"2026091109101163100_cit42","doi-asserted-by":"publisher","first-page":"4217","DOI":"10.1128\/AAC.48.11.4217-4225.2004","article-title":"OXA-60, a chromosomal, inducible,\nand imipenem-hydrolyzing class D \u03b2-lactamase from Ralstonia pickettii","volume":"48","author":"Girlich","year":"2004","journal-title":"Antimicrob. Agents Chemother."},{"issue":"2","key":"2026091109101163100_cit43","doi-asserted-by":"publisher","DOI":"10.1128\/jcm.01515-24","article-title":"Rapidly spreading\nEnterobacterales with OXA-48-like\ncarbapenemases","volume":"63","author":"Peirano","year":"2025","journal-title":"J. Clin. Microbiol."},{"key":"2026091109101163100_cit44","doi-asserted-by":"publisher","first-page":"761","DOI":"10.3390\/pathogens14080761","article-title":"Diversity in the Common Fold: Structural\nInsights into\nClass D \u03b2-Lactamases from Gram-Negative Pathogens","volume":"14","author":"Smith","year":"2025","journal-title":"Pathogens"},{"issue":"4","key":"2026091109101163100_cit45","doi-asserted-by":"publisher","first-page":"2119","DOI":"10.1128\/AAC.02522-13","article-title":"Class D\n\u03b2-lactamases: Are they all carbapenemases?","volume":"58","author":"Antunes","year":"2014","journal-title":"Antimicrob. Agents Chemother."},{"key":"2026091109101163100_cit46","doi-asserted-by":"publisher","first-page":"805","DOI":"10.1021\/acsinfecdis.5c00060","article-title":"Standardized residue numbering and secondary structure\nnomenclature in the class D \u03b2-lactamases","volume":"11","author":"Stasyuk","year":"2025","journal-title":"ACS Infect. Dis."},{"key":"2026091109101163100_cit47","doi-asserted-by":"publisher","DOI":"10.1128\/aac.00150-25","article-title":"SAND: A comprehensive\nannotation of class D \u03b2-lactamases using\nstructural alignment-based numbering","volume":"69","author":"Attana","year":"2025","journal-title":"Antimicrob.\nAgents Chemother."},{"key":"2026091109101163100_cit48","doi-asserted-by":"publisher","first-page":"15397","DOI":"10.1021\/ja051592u","article-title":"Ab initio QM\/MM study of class A \u03b2-lactamase acylation:\nDual participation of Glu166 and Lys73 in a concerted base promotion\nof Ser70","volume":"127","author":"Meroueh","year":"2005","journal-title":"J. Am. Chem. Soc."},{"key":"2026091109101163100_cit49","doi-asserted-by":"publisher","first-page":"2407","DOI":"10.1021\/ar300327a","article-title":"Class D\n\u03b2-lactamases: A reappraisal\nafter five decades","volume":"46","author":"Leonard","year":"2013","journal-title":"Acc. Chem. Res."},{"key":"2026091109101163100_cit50","doi-asserted-by":"publisher","first-page":"474","DOI":"10.1021\/acs.jmedchem.5b01215","article-title":"Exploring\nthe mechanism of \u03b2-lactam ring protonation in the class A \u03b2-lactamase\nacylation mechanism using neutron and X-ray crystallography","volume":"59","author":"Vandavasi","year":"2016","journal-title":"J. Med. Chem."},{"key":"2026091109101163100_cit51","doi-asserted-by":"publisher","first-page":"01636","DOI":"10.1128\/AAC.01636-16","article-title":"Active-site protonation\nstates in\nan acyl-enzyme intermediate of a class A \u03b2-lactamase with a\nmonobactam substrate","volume":"61","author":"Vandavasi","year":"2016","journal-title":"Antimicrob. Agents Chemother."},{"key":"2026091109101163100_cit52","doi-asserted-by":"publisher","first-page":"87","DOI":"10.1111\/febs.14315","article-title":"Mechanisms of proton\nrelay and product release by Class A \u03b2-lactamase\nat ultrahigh resolution","volume":"285","author":"Lewandowski","year":"2018","journal-title":"FEBS J."},{"key":"2026091109101163100_cit53","doi-asserted-by":"publisher","first-page":"1633","DOI":"10.1110\/ps.0302903","article-title":"Identification\nof residues critical for catalysis in a class C \u03b2-lactamase\nby combinatorial scanning mutagenesis","volume":"12","author":"Goldberg","year":"2003","journal-title":"Protein\nSci."},{"key":"2026091109101163100_cit54","doi-asserted-by":"publisher","first-page":"1282","DOI":"10.1002\/anie.201711308","article-title":"A New Mechanism\nfor \u03b2-Lactamases: Class D Enzymes Degrade 1\u03b2-Methyl Carbapenems\nthrough Lactone Formation","volume":"57","author":"Lohans","year":"2018","journal-title":"Angew. Chem. Int.\nEd."},{"key":"2026091109101163100_cit55","doi-asserted-by":"publisher","first-page":"16604","DOI":"10.1074\/jbc.RA120.014607","article-title":"Analysis\nof \u03b2-lactone formation by clinically observed carbapenemases\ninforms on a novel antibiotic resistance mechanism","volume":"295","author":"Aertker","year":"2020","journal-title":"J. Biol. Chem."},{"issue":"1","key":"2026091109101163100_cit56","doi-asserted-by":"publisher","first-page":"13608","DOI":"10.1038\/s41598-019-49264-0","article-title":"Mechanistic\ninsights into \u03b2-lactamase-catalysed carbapenem degradation through\nproduct characterisation","volume":"9","author":"Lohans","year":"2019","journal-title":"Sci. Rep."},{"key":"2026091109101163100_cit57","doi-asserted-by":"publisher","first-page":"11840","DOI":"10.1021\/bi901690r","article-title":"The 1.4\n\u00c5 crystal structure of the class D \u03b2-lactamase OXA-1 complexed\nwith doripenem","volume":"48","author":"Schneider","year":"2009","journal-title":"Biochemistry"},{"key":"2026091109101163100_cit58","doi-asserted-by":"publisher","first-page":"859","DOI":"10.1006\/jmbi.2001.4805","article-title":"Crystal structures\nof the class D \u03b2-lactamase\nOXA-13 in the native form and in complex with Meropenem","volume":"310","author":"Pernot","year":"2001","journal-title":"J. Mol. Biol."},{"key":"2026091109101163100_cit59","doi-asserted-by":"publisher","first-page":"1107","DOI":"10.1016\/j.chembiol.2013.07.015","article-title":"Structural\nbasis for carbapenemase activity of the OXA-23 \u03b2-lactamase from Acinetobacter baumannii","volume":"20","author":"Smith","year":"2013","journal-title":"Chem. Biol."},{"key":"2026091109101163100_cit60","doi-asserted-by":"publisher","first-page":"583","DOI":"10.1016\/j.jmb.2010.12.042","article-title":"Structures of the\nclass D carbapenemase OXA-24 from Acinetobacter baumanii in complex with doripenem","volume":"406","author":"Schneider","year":"2011","journal-title":"J. Mol. Biol."},{"key":"2026091109101163100_cit61","doi-asserted-by":"publisher","first-page":"273","DOI":"10.1042\/BCJ20170702","article-title":"Multiple substitutions\nlead to increased loop flexibility\nand expanded specificity in Acinetobacter baumannii carbapenemase OXA-239","volume":"475","author":"Harper","year":"2018","journal-title":"Biochem. J."},{"key":"2026091109101163100_cit62","doi-asserted-by":"publisher","first-page":"2152","DOI":"10.1002\/pro.3040","article-title":"The structure of\na doripenem-bound OXA-51 class D \u03b2-lactamase variant with enhanced\ncarbapenemase activity","volume":"25","author":"June","year":"2016","journal-title":"Protein Sci."},{"key":"2026091109101163100_cit63","doi-asserted-by":"publisher","first-page":"836","DOI":"10.1093\/jac\/dkaa513","article-title":"Class D \u03b2-lactamases","volume":"76","author":"Yoon","year":"2021","journal-title":"J.\nAntimicrob. Chemother."},{"key":"2026091109101163100_cit64","doi-asserted-by":"publisher","first-page":"801","DOI":"10.1093\/protein\/gzr041","article-title":"The Class D \u03b2-lactamase family: Residues governing\nthe maintenance and diversity of function","volume":"24","author":"Szarecka","year":"2011","journal-title":"Protein\nEng., Des. Sel."},{"key":"2026091109101163100_cit65","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.02329-19","article-title":"Role of Arginine\n214 in the Substrate Specificity of OXA-48","volume":"64","author":"Oueslati","year":"2020","journal-title":"Antimicrob. Agents Chemother."},{"key":"2026091109101163100_cit66","doi-asserted-by":"publisher","first-page":"24","DOI":"10.3390\/microorganisms8010024","article-title":"Biochemical and Structural Characterization\nof OXA-405, an OXA-48 Variant with Extended-Spectrum \u03b2-Lactamase\nActivity","volume":"8","author":"Oueslati","year":"2020","journal-title":"Microorganisms"},{"key":"2026091109101163100_cit67","doi-asserted-by":"publisher","first-page":"111","DOI":"10.1016\/j.drup.2004.02.003","article-title":"Evolution of the serine \u03b2-lactamases:\nPast, present\nand future","volume":"7","author":"Hall","year":"2004","journal-title":"Drug Resist. Updates"},{"key":"2026091109101163100_cit68","doi-asserted-by":"publisher","first-page":"32516","DOI":"10.1074\/jbc.M805375200","article-title":"A new family\nof cyanobacterial penicillin-binding\nproteins. A missing link in the evolution of class A \u03b2-lactamases","volume":"283","author":"Urbach","year":"2008","journal-title":"J. Biol. Chem."},{"key":"2026091109101163100_cit69","doi-asserted-by":"publisher","first-page":"gzab013","DOI":"10.1093\/protein\/gzab013","article-title":"Evolution\nof \u03b2-lactamases and enzyme promiscuity","volume":"34","author":"Fro\u0308hlich","year":"2021","journal-title":"Protein Eng., Des. Sel."},{"key":"2026091109101163100_cit70","doi-asserted-by":"publisher","first-page":"6132","DOI":"10.1021\/ja0013881","article-title":"The first\nstructural and mechanistic insights for class D \u03b2-lactamases:\nEvidence for a novel catalytic process for turnover of \u03b2-lactam\nantibiotics","volume":"122","author":"Golemi","year":"2000","journal-title":"J. Am. Chem. Soc."},{"key":"2026091109101163100_cit71","doi-asserted-by":"publisher","first-page":"918","DOI":"10.1038\/79688","article-title":"Crystal\nstructure of the class D\n\u03b2-lactamase OXA-10","volume":"7","author":"Paetzel","year":"2000","journal-title":"Nat. Struct. Biol."},{"key":"2026091109101163100_cit72","doi-asserted-by":"publisher","first-page":"14280","DOI":"10.1073\/pnas.241442898","article-title":"Critical involvement\nof a carbamylated lysine in catalytic function of class D \u03b2-lactamases","volume":"98","author":"Golemi","year":"2001","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"2026091109101163100_cit73","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01202-19","article-title":"Structural\ninsights into the mechanism of carbapenemase activity of the OXA-48\n\u03b2-lactamase","volume":"63","author":"Smith","year":"2019","journal-title":"Antimicrob. Agents Chemother."},{"key":"2026091109101163100_cit74","doi-asserted-by":"publisher","first-page":"495","DOI":"10.1042\/BJ20101122","article-title":"Three factors that\nmodulate the activity\nof class D \u03b2-lactamases and interfere with the post-translational\ncarboxylation of Lys70","volume":"432","author":"Vercheval","year":"2010","journal-title":"Biochem. J."},{"key":"2026091109101163100_cit75","doi-asserted-by":"publisher","first-page":"333","DOI":"10.1128\/AAC.01483-13","article-title":"Structural\norigins of oxacillinase specificity in class D \u03b2-lactamases","volume":"58","author":"June","year":"2014","journal-title":"Antimicrob. Agents Chemother."},{"key":"2026091109101163100_cit76","doi-asserted-by":"publisher","first-page":"1976","DOI":"10.1021\/bi501547k","article-title":"Structural basis\nof activity against aztreonam and extended spectrum cephalosporins\nfor two carbapenem-hydrolyzing class D \u03b2-lactamases from Acinetobacter baumannii","volume":"54","author":"Mitchell","year":"2015","journal-title":"Biochemistry"},{"key":"2026091109101163100_cit77","doi-asserted-by":"publisher","first-page":"145","DOI":"10.3390\/antibiotics8030145","article-title":"Structural Analysis of the OXA-48 Carbapenemase Bound to a \u201cPoor\u201d\nCarbapenem Substrate, Doripenem","volume":"8","author":"Papp-Wallace","year":"2019","journal-title":"Antibiotics"},{"key":"2026091109101163100_cit78","doi-asserted-by":"publisher","first-page":"445","DOI":"10.1021\/acsinfecdis.0c00798","article-title":"Mechanistic\nbasis of OXA-48-like \u03b2-lactamases\u2019\nhydrolysis of carbapenems","volume":"7","author":"Stojanoski","year":"2021","journal-title":"ACS Infect. Dis."},{"key":"2026091109101163100_cit79","doi-asserted-by":"publisher","first-page":"102127","DOI":"10.1016\/j.jbc.2022.102127","article-title":"Conformational flexibility\nin carbapenem hydrolysis drives substrate specificity of the class\nD carbapenemase OXA-24\/40","volume":"298","author":"Mitchell","year":"2022","journal-title":"J. Biol. Chem."},{"issue":"12","key":"2026091109101163100_cit80","doi-asserted-by":"publisher","first-page":"168603","DOI":"10.1016\/j.jmb.2024.168603","article-title":"Structural\nand dynamic features of Acinetobacter baumannii OXA-66\n\u03b2-lactamase explain\nits stability and evolution of novel variants","volume":"436","author":"Klamer","year":"2024","journal-title":"J. Mol. Biol."},{"key":"2026091109101163100_cit81","doi-asserted-by":"publisher","first-page":"1289","DOI":"10.1016\/S0969-2126(00)00534-7","article-title":"Insights Into class D \u03b2-lactamases\nare revealed by the crystal structure of the OXA10 enzyme from Pseudomonas aeruginosa","volume":"8","author":"Maveyraud","year":"2000","journal-title":"Structure"},{"key":"2026091109101163100_cit82","doi-asserted-by":"publisher","first-page":"82","DOI":"10.1110\/ps.0224303","article-title":"Comparison\nof \u03b2-lactamases of classes A and D: 1.5-\u00c5 crystallographic\nstructure of the class D OXA-1 oxacillinase","volume":"12","author":"Sun","year":"2003","journal-title":"Protein Sci."},{"key":"2026091109101163100_cit83","doi-asserted-by":"publisher","first-page":"540","DOI":"10.1016\/j.chembiol.2009.04.010","article-title":"Crystal structure of\nthe OXA-48 \u03b2-lactamase reveals mechanistic diversity among class\nD carbapenemases","volume":"16","author":"Docquier","year":"2009","journal-title":"Chem. Biol."},{"key":"2026091109101163100_cit84","doi-asserted-by":"publisher","first-page":"13320","DOI":"10.1021\/ja104092z","article-title":"Design,\nsynthesis, and crystal structures of 6-alkylidene-2\u2019-substituted\npenicillanic acid sulfones as potent inhibitors of Acinetobacter baumannii OXA-24 carbapenemase","volume":"132","author":"Bou","year":"2010","journal-title":"J.\nAm. Chem. Soc."},{"key":"2026091109101163100_cit85","doi-asserted-by":"publisher","first-page":"2167","DOI":"10.1128\/AAC.01517-09","article-title":"Crystal structure of\nthe narrow-spectrum OXA-46 class D \u03b2-lactamase: relationship\nbetween active-site lysine carbamylation and inhibition by polycarboxylates","volume":"54","author":"Docquier","year":"2010","journal-title":"Antimicrob. Agents Chemother."},{"key":"2026091109101163100_cit86","doi-asserted-by":"publisher","first-page":"2135","DOI":"10.1128\/AAC.01983-13","article-title":"Crystal\nStructure of Carbapenemase OXA-58 from Acinetobacter baumannii","volume":"58","author":"Smith","year":"2014","journal-title":"Antimicrob. Agents Chemother."},{"key":"2026091109101163100_cit87","doi-asserted-by":"publisher","first-page":"1791","DOI":"10.1021\/acschembio.5b00090","article-title":"Structural basis for enhancement\nof carbapenemase activity in the OXA-51 family of class D \u03b2-lactamases","volume":"10","author":"Smith","year":"2015","journal-title":"ACS Chem. Biol."},{"key":"2026091109101163100_cit88","doi-asserted-by":"publisher","first-page":"3370","DOI":"10.1021\/acs.biochem.5b00298","article-title":"Structural\nbasis for different substrate profiles of two closely related class\nD \u03b2-lactamases and their inhibition by halogens","volume":"54","author":"Stojanoski","year":"2015","journal-title":"Biochemistry"},{"key":"2026091109101163100_cit89","doi-asserted-by":"publisher","first-page":"692","DOI":"10.1107\/S2059798317008671","article-title":"The role of conserved surface hydrophobic\nresidues\nin the carbapenemase activity of the class D \u03b2-lactamases","volume":"D73","author":"Toth","year":"2017","journal-title":"Acta Crystallogr."},{"key":"2026091109101163100_cit90","doi-asserted-by":"publisher","first-page":"579","DOI":"10.1107\/S2053230X17013838","article-title":"Structure,\nactivity\nand thermostability investigations of OXA-163, OXA-181 and OXA-245\nusing biochemical analysis, crystal structures and differential scanning\ncalorimetry analysis","volume":"F73","author":"Lund","year":"2017","journal-title":"Acta Crystallogr."},{"issue":"34","key":"2026091109101163100_cit91","doi-asserted-by":"publisher","first-page":"3604","DOI":"10.1021\/acs.biochem.9b00365","article-title":"Importance of the\n\u03b25\u2212\u03b26 Loop for the Structure, Catalytic Efficiency,\nand Stability of Carbapenem-Hydrolyzing Class D \u03b2-Lactamase\nSubfamily OXA-143","volume":"58","author":"Antunes","year":"2019","journal-title":"Biochemistry"},{"key":"2026091109101163100_cit92","doi-asserted-by":"publisher","first-page":"107544","DOI":"10.1016\/j.jsb.2020.107544","article-title":"A surface\nloop modulates activity of the bacillus class D \u03b2-lactamases","volume":"211","author":"Stewart","year":"2020","journal-title":"J. Struct. Biol."},{"issue":"10","key":"2026091109101163100_cit93","doi-asserted-by":"publisher","DOI":"10.1128\/aac.00985-22","article-title":"Functional and structural\ncharacterization of OXA-935, a novel OXA-10-family \u03b2-lactamase\nfrom Pseudomonas aeruginosa","volume":"66","author":"Pincus","year":"2022","journal-title":"Antimicrob. Agents Chemother."},{"issue":"47","key":"2026091109101163100_cit94","doi-asserted-by":"publisher","first-page":"11252","DOI":"10.1021\/bi901548c","article-title":"Critical Role of Tryptophan 154 for the\nActivity and Stability of Class D \u03b2-Lactamases","volume":"48","author":"Baurin","year":"2009","journal-title":"Biochemistry"},{"key":"2026091109101163100_cit95","doi-asserted-by":"publisher","first-page":"395","DOI":"10.1093\/jac\/dkv375","article-title":"Structural\ninsights into the loss of penicillinase and the gain of ceftazidimase\nactivities by OXA-145 \u03b2-lactamase in Pseudomonas aeruginosa","volume":"71","author":"Meziane-Cherif","year":"2016","journal-title":"J. Antimicrob. Chemother."},{"key":"2026091109101163100_cit96","doi-asserted-by":"publisher","first-page":"499","DOI":"10.1038\/s41929-024-01117-4","article-title":"Epistasis\narises from shifting the rate-limiting step during enzyme evolution\nof a \u03b2-lactamase","volume":"7","author":"Fro\u0308hlich","year":"2024","journal-title":"Nat. Catal."},{"key":"2026091109101163100_cit97","doi-asserted-by":"publisher","first-page":"634","DOI":"10.1016\/j.ejmech.2017.12.085","article-title":"A focused fragment\nlibrary targeting the antibiotic resistance enzyme Oxacillinase-48:\nSynthesis, structural evaluation and inhibitor design","volume":"145","author":"Akhter","year":"2018","journal-title":"Eur. J. Med. Chem."},{"key":"2026091109101163100_cit98","doi-asserted-by":"publisher","first-page":"261","DOI":"10.1021\/acsinfecdis.9b00304","article-title":"Structural Basis for\nSubstrate Specificity\nand Carbapenemase Activity of OXA-48 Class D \u03b2-Lactamase","volume":"6","author":"Akhtar","year":"2020","journal-title":"ACS Infect. Dis."},{"key":"2026091109101163100_cit99","doi-asserted-by":"publisher","DOI":"10.1101\/2024.12.23.630153","article-title":"Structure and dynamics of Burkholderia pseudomallei OXA-57, a distinctive\nlow efficiency class D \u03b2-lactamase with carbapenem-hydrolyzing\nactivity","author":"Bragginton","year":"2024","journal-title":"bioRxiv"},{"key":"2026091109101163100_cit100","doi-asserted-by":"publisher","first-page":"1177","DOI":"10.1002\/prot.25039","article-title":"Molprobity\u2019s ultimate rotamer-library distributions\nfor model validation","volume":"84","author":"Hintze","year":"2016","journal-title":"Proteins"},{"issue":"10","key":"2026091109101163100_cit101","doi-asserted-by":"publisher","DOI":"10.1128\/aac.00918-25","article-title":"Dual mechanism\nof the OXA-23 carbapenemase inhibition by the carbapenem NA-1-157","volume":"69","author":"Toth","year":"2025","journal-title":"Antimicrob. Agents Chemother."},{"key":"2026091109101163100_cit102","doi-asserted-by":"publisher","first-page":"515","DOI":"10.1002\/pro.3100","article-title":"Exploring the potential of boronic acids as inhibitors\nof OXA-24\/40 \u03b2-lactamase","volume":"26","author":"Werner","year":"2017","journal-title":"Protein Sci."},{"key":"2026091109101163100_cit103","doi-asserted-by":"publisher","first-page":"644","DOI":"10.3390\/antibiotics12040644","article-title":"Sulfonamidoboronic\nacids as \u201ccross-class\u201d\ninhibitors of an expanded-spectrum class C cephalosporinase, ADC-33,\nand a class d carbapenemase, OXA-24\/40: Strategic compound design\nto combat resistance in Acinetobacter baumannii","volume":"12","author":"Introvigne","year":"2023","journal-title":"Antibiotics"},{"issue":"10","key":"2026091109101163100_cit104","doi-asserted-by":"publisher","first-page":"4848","DOI":"10.1128\/AAC.00762-13","article-title":"Structures\nof the\nClass D Carbapenemases OXA-23 and OXA-146: Mechanistic Basis of Activity\nagainst Carbapenems, Extended-Spectrum Cephalosporins, and Aztreonam","volume":"57","author":"Kaitany","year":"2013","journal-title":"Antimicrob. Agents Chemother."},{"key":"2026091109101163100_cit105","doi-asserted-by":"publisher","first-page":"175","DOI":"10.1021\/acsinfecdis.5b00007","article-title":"Molecular mechanism of avibactam-mediated \u03b2-lactamase\ninhibition","volume":"1","author":"King","year":"2015","journal-title":"ACS Infect. Dis."},{"key":"2026091109101163100_cit106","doi-asserted-by":"publisher","first-page":"6024","DOI":"10.1039\/C7OB01514C","article-title":"13C-Carbamylation as a mechanistic\nprobe for the inhibition of class D \u03b2-lactamases by avibactam\nand halide ions","volume":"15","author":"Lohans","year":"2017","journal-title":"Org. Biomol. Chem."},{"key":"2026091109101163100_cit107","doi-asserted-by":"publisher","first-page":"591","DOI":"10.1021\/cb500703p","article-title":"Molecular Basis\nof Selective Inhibition\nand Slow Reversibility of Avibactam against Class D Carbapenemases:\nA Structure-Guided Study of OXA-24 and OXA-48","volume":"10","author":"Lahiri","year":"2015","journal-title":"ACS Chem. Biol."},{"key":"2026091109101163100_cit108","doi-asserted-by":"publisher","first-page":"4067","DOI":"10.1021\/acs.jmedchem.8b00091","article-title":"Strategic Approaches\nto Overcome Resistance against Gram-Negative Pathogens Using \u03b2-Lactamase\nInhibitors and \u03b2-Lactam Enhancers: Activity of Three Novel Diazabicyclooctanes\nWCK 5153, Zidebactam (WCK 5107), and WCK 4234","volume":"61","author":"Papp-Wallace","year":"2018","journal-title":"J. Med. Chem."},{"key":"2026091109101163100_cit109","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.00159-19","article-title":"Targeting Multidrug-Resistant\nAcinetobacter spp.: Sulbactam and the Diazabicyclooctenone \u03b2-Lactamase\nInhibitor ETX2514 as a Novel Therapeutic Agent","volume":"10","author":"Barnes","year":"2019","journal-title":"mBio"},{"key":"2026091109101163100_cit110","doi-asserted-by":"publisher","first-page":"864","DOI":"10.1021\/acschembio.5b00944","article-title":"Structural and kinetic characterization of diazabicyclooctanes\nas dual inhibitors of both serine-\u03b2-lactamases and penicillin-binding\nproteins","volume":"11","author":"King","year":"2016","journal-title":"ACS Chem. Biol."},{"key":"2026091109101163100_cit111","doi-asserted-by":"publisher","first-page":"15802","DOI":"10.1021\/acs.jmedchem.0c01535","article-title":"Discovery of ANT3310, a Novel Broad-Spectrum\nSerine \u03b2-Lactamase Inhibitor of the Diazabicyclooctane Class,\nWhich Strongly Potentiates Meropenem Activity against Carbapenem-Resistant Enterobacterales and Acinetobacter baumannii","volume":"63","author":"Davies","year":"2020","journal-title":"J. Med. Chem."},{"key":"2026091109101163100_cit112","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1128\/AAC.01393-15","article-title":"Active-site plasticity is essential\nto carbapenem hydrolysis\nby OXA-58 class D \u03b2-lactamase of Acinetobacter baumannii","volume":"60","author":"Pratap","year":"2016","journal-title":"Antimicrob. Agents Chemother."},{"key":"2026091109101163100_cit113","doi-asserted-by":"publisher","first-page":"2396","DOI":"10.1021\/acsinfecdis.6c00415","article-title":"The novel\ncarbapenem, JDB\/PQ-1\u2013219, has potent broad spectrum activity\nagainst multi-drug resistant Acinetobacter baumannii","volume":"12","author":"Toth","year":"2026","journal-title":"ACS Infect. Dis."},{"key":"2026091109101163100_cit114","doi-asserted-by":"publisher","first-page":"4347","DOI":"10.1021\/acsinfecdis.4c00671","article-title":"Decarboxylation\nof the Catalytic Lysine Residue by the C5\u03b1-Methyl-Substituted\nCarbapenem NA-1\u2013157 Leads to Potent Inhibition of the OXA-58\nCarbapenemase","volume":"10","author":"Toth","year":"2024","journal-title":"ACS Infect. Dis."},{"key":"2026091109101163100_cit115","doi-asserted-by":"publisher","first-page":"5191","DOI":"10.1021\/acs.biochem.6b00461","article-title":"Insight into\nthe mechanism\nof hydrolysis of Meropenem by OXA-23 serine-\u03b2-lactamase gained\nby quantum mechanics\/molecular mechanics calculations Biochemistry","volume":"55","author":"Sgrignani","year":"2016","journal-title":"Biochemistry"},{"key":"2026091109101163100_cit116","doi-asserted-by":"publisher","first-page":"3285","DOI":"10.1021\/acs.jpcb.6b07884","article-title":"A distal disulfide bridge in OXA-1\n\u03b2-lactamase\nstabilizes the catalytic center and alters the dynamics of the specificity\ndetermining \u03a9 loop","volume":"121","author":"Simakov","year":"2017","journal-title":"J. Phys. Chem. B"},{"key":"2026091109101163100_cit117","doi-asserted-by":"publisher","first-page":"9356","DOI":"10.1021\/acsomega.0c00356","article-title":"Structure-based screening of non-\u03b2-lactam\ninhibitors against class D \u03b2-lactamases: An approach of docking\nand molecular dynamics","volume":"5","author":"Gupta","year":"2020","journal-title":"ACS Omega"},{"key":"2026091109101163100_cit118","doi-asserted-by":"publisher","first-page":"6188","DOI":"10.1021\/acscatal.0c00596","article-title":"Small changes in hydration determine cephalosporinase\nactivity of OXA-48 \u03b2-lactamases","volume":"10","author":"Hirvonen","year":"2020","journal-title":"ACS Catal."},{"key":"2026091109101163100_cit119","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00184-21","article-title":"Antimicrobial\nresistance conferred by OXA-48 \u03b2-lactamases: Towards a detailed\nmechanistic understanding","volume":"65","author":"Hirvonen","year":"2021","journal-title":"Antimicrob. Agents\nChemother."},{"key":"2026091109101163100_cit120","doi-asserted-by":"publisher","first-page":"24319","DOI":"10.1039\/D2RA02939A","article-title":"OXA-376\nand OXA-530\nvariants of \u03b2-lactamase: computational study uncovers potential\ntherapeutic targets of Acinetobacter baumannii","volume":"12","author":"Halder","year":"2022","journal-title":"RSC Adv."},{"key":"2026091109101163100_cit121","doi-asserted-by":"publisher","first-page":"4534","DOI":"10.1021\/acscatal.1c05694","article-title":"Multiscale simulations identify origins\nof differential carbapenem hydrolysis by the OXA-48 \u03b2-lactamase","volume":"12","author":"Hirvonen","year":"2022","journal-title":"ACS Catal."},{"issue":"3","key":"2026091109101163100_cit122","doi-asserted-by":"publisher","DOI":"10.1128\/mbio.00367-22","article-title":"C6 Hydroxymethyl-Substituted Carbapenem\nMA-1-206 Inhibits the Major Acinetobacter baumannii Carbapenemase OXA-23 by Impeding Deacylation","volume":"13","author":"Stewart","year":"2022","journal-title":"mBio"},{"key":"2026091109101163100_cit123","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1021\/acsinfecdis.6c00512","article-title":"Deciphering the role of the non-active site ancillary\nresidues in maintaining the activity and substrate specificity of\nOXA-232 beta-lactamase","author":"Ajith","year":"2026","journal-title":"ACS Infect. Dis."},{"key":"2026091109101163100_cit124","doi-asserted-by":"publisher","DOI":"10.64898\/2026.04.15.718664","article-title":"Acyl-enzyme dynamics,\ntautomerisation and hydration regulate turnover of carbapenem antibiotics\nby the OXA-48 \u03b2-lactamase.","author":"Hoff","year":"2026","journal-title":"bioRxiv"},{"key":"2026091109101163100_cit125","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.02191-18","article-title":"Role of the hydrophobic bridge in\nthe carbapenemase\nactivity of class D \u03b2-lactamases","volume":"63","author":"Stewart","year":"2019","journal-title":"Antimicrob.\nAgents Chemother."},{"key":"2026091109101163100_cit126","doi-asserted-by":"publisher","first-page":"1821","DOI":"10.1002\/2211-5463.12935","article-title":"Structural insights\ninto the enhanced carbapenemase efficiency of OXA-655 compared to\nOXA-10","volume":"10","author":"Leiros","year":"2020","journal-title":"FEBS Open Bio"},{"issue":"1","key":"2026091109101163100_cit127","doi-asserted-by":"publisher","first-page":"2412631","DOI":"10.1080\/22221751.2024.2412631","article-title":"Structural insights\ninto alterations in the substrate\nspectrum of serine-\u03b2-lactamase OXA-10 from Pseudomonas aeruginosa by single amino acid substitutions","volume":"13","author":"Lee","year":"2024","journal-title":"Emerg. Microbes Infect."},{"issue":"9","key":"2026091109101163100_cit128","doi-asserted-by":"publisher","first-page":"17104","DOI":"10.1038\/nmicrobiol.2017.104","article-title":"ETX2514\nis a broad-spectrum \u03b2-lactamase inhibitor for the treatment\nof drug-resistant Gram-negative bacteria including Acinetobacter baumannii","volume":"2","author":"Durand-Re\u0301ville","year":"2017","journal-title":"Nat. Microbiol."},{"key":"2026091109101163100_cit129","doi-asserted-by":"publisher","first-page":"1164","DOI":"10.1021\/acsinfecdis.0c00714","article-title":"Inhibition of the Clostridioides difficile class D \u03b2-lactamase CDD-1 by avibactam","volume":"7","author":"Stewart","year":"2021","journal-title":"ACS Infect. Dis."},{"key":"2026091109101163100_cit130","doi-asserted-by":"publisher","first-page":"5354","DOI":"10.1073\/pnas.0607557104","article-title":"Crystal structure\nof the carbapenemase OXA-24 reveals insights into the mechanism of\ncarbapenem hydrolysis","volume":"104","author":"Santillana","year":"2007","journal-title":"Proc. Natl. Acad. Sci.\nU. S. A."},{"key":"2026091109101163100_cit131","doi-asserted-by":"publisher","first-page":"626","DOI":"10.1093\/jac\/dkaa488","article-title":"Characterization\nof the novel OXA-213-like \u03b2-lactamase OXA-822 from Acinetobacter calcoaceticus","volume":"76","author":"Tietgen","year":"2021","journal-title":"J. Antimicrob. Chemother."},{"key":"2026091109101163100_cit132","doi-asserted-by":"publisher","first-page":"6136","DOI":"10.1021\/bi900448u","article-title":"Mutation of the\nactive site carboxy-lysine\n(K70) of OXA-1 \u03b2-lactamase results in a deacylation-deficient\nenzyme","volume":"48","author":"Schneider","year":"2009","journal-title":"Biochemistry"},{"key":"2026091109101163100_cit133","doi-asserted-by":"publisher","first-page":"598","DOI":"10.1038\/s41579-024-01054-w","article-title":"ESKAPE pathogens:\nantimicrobial resistance,\nepidemiology, clinical impact and therapeutics","volume":"22","author":"Miller","year":"2024","journal-title":"Nat. Rev. Microbiol."},{"key":"2026091109101163100_cit134","doi-asserted-by":"publisher","first-page":"491","DOI":"10.1038\/s41579-025-01169-8","article-title":"The global resistance problem and\nthe clinical antibacterial\npipeline","volume":"23","author":"Theuretzbacher","year":"2025","journal-title":"Nat. Rev. Microbiol."},{"key":"2026091109101163100_cit135","doi-asserted-by":"publisher","first-page":"168","DOI":"10.3390\/pathogens14020168","article-title":"\u0392-lactam\/\u03b2-lactamase\ninhibitor combination antibiotics under development","volume":"14","author":"Katsarou","year":"2025","journal-title":"Pathogens"},{"issue":"2","key":"2026091109101163100_cit136","doi-asserted-by":"publisher","DOI":"10.1128\/aac.01614-24","article-title":"Advancements in the\nfight against globally distributed OXA-48 carbapenemase:\nEvaluating the new generation of carbapenemase inhibitors","volume":"69","author":"Outeda-Garci\u0301a","year":"2025","journal-title":"Antimicrob. Agents Chemother."},{"key":"2026091109101163100_cit137","doi-asserted-by":"publisher","first-page":"dkaf467","DOI":"10.1093\/jac\/dkaf467","article-title":"In vitro activity\nof cefepime\/zidebactam against sulbactam\/durlobactam-susceptible and\n-resistant Acinetobacter baumannii clinical isolates","volume":"81","author":"Tascini","year":"2026","journal-title":"J. Antimicrob. Chemother."},{"key":"2026091109101163100_cit138","doi-asserted-by":"publisher","DOI":"10.1128\/aac.01691-25","article-title":"Disarming carbapenemase-producing Acinetobacter baumannii: High potency of the novel therapeutic combination of Meropenem\nand the innovative diazabicyclooctane \u03b2-lactamase inhibitor\npilabactam (formerly ANT3310)","volume":"70","author":"Rodri\u0301guez-Pallares","year":"2026","journal-title":"Antimicrob. Agents\nChemother."},{"issue":"29","key":"2026091109101163100_cit139","doi-asserted-by":"publisher","first-page":"11663","DOI":"10.1073\/pnas.1205073109","article-title":"Avibactam is a covalent,\nreversible, non\u2212\u03b2-lactam \u03b2-lactamase inhibitor","volume":"109","author":"Ehmann","year":"2012","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"2026091109101163100_cit140","doi-asserted-by":"publisher","first-page":"2321","DOI":"10.1093\/jac\/dkac171","article-title":"The primary\npharmacology of ceftazidime\/avibactam: in vitro translational\nbiology","volume":"77","author":"Nichols","year":"2022","journal-title":"J. Antimicrob. Chemother."},{"issue":"4","key":"2026091109101163100_cit141","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.02260-16","article-title":"Cyclic Boronates Inhibit\nAll Classes of \u03b2-Lactamases","volume":"61","author":"Cahill","year":"2017","journal-title":"Antimicrob.\nAgents Chemother."},{"key":"2026091109101163100_cit142","doi-asserted-by":"publisher","first-page":"8544","DOI":"10.1021\/acs.jmedchem.9b00911","article-title":"Bicyclic boronate VNRX-5133 inhibits\nmetallo- and serine-\u03b2-lactamases","volume":"62","author":"Krajnc","year":"2019","journal-title":"J. Med.\nChem."},{"key":"2026091109101163100_cit143","doi-asserted-by":"publisher","first-page":"101","DOI":"10.1016\/j.cbpa.2019.03.001","article-title":"Will morphing\nboron-based inhibitors\nbeat the \u03b2-lactamases?","volume":"50","author":"Krajnc","year":"2019","journal-title":"Curr. Opin. Chem.\nBiol."},{"key":"2026091109101163100_cit144","doi-asserted-by":"publisher","first-page":"528","DOI":"10.3390\/antibiotics14050528","article-title":"Breaking through\nresistance: A comparative review of new \u03b2-lactamase inhibitors\n(avibactam, vaborbactam, relebactam) against multidrug-resistant superbugs","volume":"14","author":"Karaiskos","year":"2025","journal-title":"Antibiotics"},{"key":"2026091109101163100_cit145","doi-asserted-by":"publisher","DOI":"10.71150\/jm.2510019","article-title":"Structural\nperspectives\non clinical \u03b2-lactamase inhibitors: From mechanism to resistance","volume":"64","author":"Park","year":"2026","journal-title":"J. Microbiol."},{"key":"2026091109101163100_cit146","doi-asserted-by":"publisher","first-page":"1123","DOI":"10.1021\/acsinfecdis.3c00059","article-title":"The C5\u03b1-methyl-substituted\ncarbapenem NA-1\u2013157 exhibits potent activity against Klebsiella spp. isolates producing OXA-48-type carbapenemases","volume":"9","author":"Smith","year":"2023","journal-title":"ACS Infect. Dis."},{"key":"2026091109101163100_cit147","doi-asserted-by":"publisher","first-page":"1232","DOI":"10.1021\/acsinfecdis.3c00683","article-title":"Restricted\nrotational flexibility of the C5\u03b1-methyl-substituted carbapenem\nNA-1\u2013157 leads to potent inhibition of the GES-5 carbapenemase","volume":"10","author":"Stewart","year":"2024","journal-title":"ACS Infect. Dis."},{"key":"2026091109101163100_cit148","doi-asserted-by":"publisher","first-page":"1521","DOI":"10.1021\/acsinfecdis.2c00152","article-title":"QM\/MM Simulations\nReveal the Determinants of Carbapenemase Activity in Class A \u03b2-Lactamases","volume":"8","author":"Chudyk","year":"2022","journal-title":"ACS Infect. Dis."},{"key":"2026091109101163100_cit149","doi-asserted-by":"publisher","first-page":"379","DOI":"10.1016\/0022-2836(71)90324-X","article-title":"The interpretation of protein structures:\nEstimation\nof static accessibility","volume":"55","author":"Lee","year":"1971","journal-title":"J. Mol. Biol."}],"container-title":["ACS Infectious Diseases"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pubs.acs.org\/doi\/pdf\/10.1021\/acsinfecdis.6c00611","content-type":"application\/pdf","content-version":"vor","intended-application":"unspecified"},{"URL":"https:\/\/pubs.acs.org\/aidcbc\/article-pdf\/12\/9\/2965\/67426723\/acsinfecdis.6c00611.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pubs.acs.org\/aidcbc\/article-pdf\/12\/9\/2965\/67426723\/acsinfecdis.6c00611.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T13:32:23Z","timestamp":1789133543000},"score":1,"resource":{"primary":{"URL":"https:\/\/pubs.acs.org\/aidcbc\/article\/12\/9\/2965\/5330457\/Molecular-Architecture-and-Catalytic-Mechanisms-of"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,26]]},"references-count":149,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2026,8,26]]},"published-print":{"date-parts":[[2026,9,11]]}},"URL":"https:\/\/doi.org\/10.1021\/acsinfecdis.6c00611","relation":{},"ISSN":["2373-8227"],"issn-type":[{"value":"2373-8227","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,26]]}}}