ArticleAntimicrobial agents and chemotherapy2013
Structures of the class D Carbapenemases OXA-23 and OXA-146: mechanistic basis of activity against carbapenems, extended-spectrum cephalosporins, and aztreonam.
Article in Antimicrobial agents and chemotherapy, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers, 1 of them a synthesis that pooled it.
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Who cites it
57 citing papers in PubMed, 1 synthesis or guideline pooled it, 91 citations in OpenAlex.
- Structural basis for carbapenem-hydrolyzing mechanisms of carbapenemases conferring antibiotic resistance.International journal of molecular sciences · 2015Pooled it
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- Carbapenem resistance genes and biofilm-virulence uncoupling inFrontiers in antibiotics · 2026Article
- Structural insights into the activity of carbapenemases: understanding the mechanism of action of current inhibitors and informing the design of new carbapenem adjuvants.RSC medicinal chemistry · 2025Review
- Structural comparison of substrate-binding pockets of serine β-lactamases in classes A, C, and D.Journal of enzyme inhibition and medicinal chemistry · 2025Review
- Dissemination of OXA-23 carbapenemase-producingMicrobial genomics · 2025Article
- Diversity in the Common Fold: Structural Insights into Class D β-Lactamases from Gram-Negative Pathogens.Pathogens (Basel, Switzerland) · 2025Article
- SAND: a comprehensive annotation of class D β-lactamases using structural alignment-based numbering.Antimicrobial agents and chemotherapy · 2025Article
- Clinical outcomes of phenotype-guided treatment in group D carbapenemase-producingMicrobiology spectrum · 2025Article
- A microbiological and structural analysis of the interplay between sulbactam/durlobactam and imipenem against penicillin-binding proteins (PBPs) ofAntimicrobial agents and chemotherapy · 2025Article
- Structural insights into alterations in the substrate spectrum of serine-β-lactamase OXA-10 fromEmerging microbes & infections · 2024Article
- Agents Targeting the Bacterial Cell Wall as Tools to Combat Gram-Positive Pathogens.Molecules (Basel, Switzerland) · 2024Review
- Structural and Dynamic Features of Acinetobacter baumannii OXA-66 β-Lactamase Explain Its Stability and Evolution of Novel Variants.Journal of molecular biology · 2024Article
- The Dynamics of OXA-23 β-Lactamase fromInternational journal of molecular sciences · 2023Article
- Molecular drivers of resistance to sulbactam-durlobactam in contemporary clinical isolates ofAntimicrobial agents and chemotherapy · 2023Article
- Two non-active site residues W165 and L166 prominently influence the beta-lactam hydrolytic ability of OXA-23 beta-lactamase.The Journal of antibiotics · 2023Article
- Synthesis of a Novel Boronic Acid Transition State Inhibitor, MB076: A Heterocyclic Triazole Effectively InhibitsJournal of medicinal chemistry · 2023Article
- A review on the mechanistic details of OXA enzymes of ESKAPE pathogens.Pathogens and global health · 2023Review
- Sulfonamidoboronic Acids as "Cross-Class" Inhibitors of an Expanded-Spectrum Class C Cephalosporinase, ADC-33, and a Class D Carbapenemase, OXA-24/40: Strategic Compound Design to Combat Resistance inAntibiotics (Basel, Switzerland) · 2023Article
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7 authors at 2 institutions in 1 country.
Funding
Abstract
Class D β-lactamases that hydrolyze carbapenems such as imipenem and doripenem are a recognized danger to the efficacy of these "last-resort" β-lactam antibiotics. Like all known class D carbapenemases, OXA-23 cannot hydrolyze the expanded-spectrum cephalosporin ceftazidime. OXA-146 is an OXA-23 subfamily clinical variant that differs from the parent enzyme by a single alanine (A220) inserted in the loop connecting β-strands β5 and β6. We discovered that this insertion enables OXA-146 to bind and hydrolyze ceftazidime with an efficiency comparable to those of other extended-spectrum class D β-lactamases. OXA-146 also binds and hydrolyzes aztreonam, cefotaxime, ceftriaxone, and ampicillin with higher efficiency than OXA-23 and preserves activity against doripenem. In this study, we report the X-ray crystal structures of both the OXA-23 and OXA-146 enzymes at 1.6-Å and 1.2-Å resolution. A comparison of the two structures shows that the extra alanine moves a methionine (M221) out of its normal position, where it forms a bridge over the top of the active site. This single amino acid insertion also lengthens the β5-β6 loop, moving the entire backbone of this region further away from the active site. A model of ceftazidime bound in the active site reveals that these two structural alterations are both likely to relieve steric clashes between the bulky R1 side chain of ceftazidime and OXA-23. With activity against all four classes of β-lactam antibiotics, OXA-146 represents an alarming new threat to the treatment of infections caused by Acinetobacter spp.
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