ArticleBiochemistry2015
Structural basis of activity against aztreonam and extended spectrum cephalosporins for two carbapenem-hydrolyzing class D β-lactamases from Acinetobacter baumannii.
Article in Biochemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
22 citing papers in PubMed, 38 citations in OpenAlex.
- Structural comparison of substrate-binding pockets of serine β-lactamases in classes A, C, and D.Journal of enzyme inhibition and medicinal chemistry · 2025Review
- Diversity in the Common Fold: Structural Insights into Class D β-Lactamases from Gram-Negative Pathogens.Pathogens (Basel, Switzerland) · 2025Article
- Simultaneous enhancement of multiple functional properties using evolution-informed protein design.Nature communications · 2024Article
- 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
- 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
- Simultaneous enhancement of multiple functional properties using evolution-informed protein design.bioRxiv : the preprint server for biology · 2023Article
- 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
- Resistance to aztreonam-avibactam due to CTX-M-15 in the presence of penicillin-binding protein 3 with extra amino acids inFrontiers in microbiology · 2022Article
- β-Lactam antibiotic targets and resistance mechanisms: from covalent inhibitors to substrates.RSC medicinal chemistry · 2021Review
- Arginine Modulates Carbapenem Deactivation by OXA-24/40 in Acinetobacter baumannii.Journal of molecular biology · 2021Article
- Antimicrobial Resistance Conferred by OXA-48 β-Lactamases: Towards a Detailed Mechanistic Understanding.Antimicrobial agents and chemotherapy · 2021Review
- Can We Exploit β-Lactamases Intrinsic Dynamics for Designing More Effective Inhibitors?Antibiotics (Basel, Switzerland) · 2020Review
- Structural Analysis of The OXA-48 Carbapenemase Bound to A "Poor" Carbapenem Substrate, Doripenem.Antibiotics (Basel, Switzerland) · 2019Article
- Crystal Structure of Phosphoserine BlaC fromInternational journal of molecular sciences · 2019Article
- Intrinsic Class D β-Lactamases ofmBio · 2018Article
- Multiple substitutions lead to increased loop flexibility and expanded specificity inThe Biochemical journal · 2018Article
- A gratuitous β-Lactamase inducer uncovers hidden active site dynamics of the Staphylococcus aureus BlaR1 sensor domain.PloS one · 2018Article
- Kinetic characterization of GES-22 β-lactamase harboring the M169L clinical mutation.The Journal of antibiotics · 2016Article
- The structure of a doripenem-bound OXA-51 class D β-lactamase variant with enhanced carbapenemase activity.Protein science : a publication of the Protein Society · 2016Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 3 institutions in 1 country.
Funding
Abstract
The carbapenem-hydrolyzing class D β-lactamases OXA-23 and OXA-24/40 have emerged worldwide as causative agents for β-lactam antibiotic resistance in Acinetobacter species. Many variants of these enzymes have appeared clinically, including OXA-160 and OXA-225, which both contain a P → S substitution at homologous positions in the OXA-24/40 and OXA-23 backgrounds, respectively. We purified OXA-160 and OXA-225 and used steady-state kinetic analysis to compare the substrate profiles of these variants to their parental enzymes, OXA-24/40 and OXA-23. OXA-160 and OXA-225 possess greatly enhanced hydrolytic activities against aztreonam, ceftazidime, cefotaxime, and ceftriaxone when compared to OXA-24/40 and OXA-23. These enhanced activities are the result of much lower Km values, suggesting that the P → S substitution enhances the binding affinity of these drugs. We have determined the structures of the acylated forms of OXA-160 (with ceftazidime and aztreonam) and OXA-225 (ceftazidime). These structures show that the R1 oxyimino side-chain of these drugs occupies a space near the β5-β6 loop and the omega loop of the enzymes. The P → S substitution found in OXA-160 and OXA-225 results in a deviation of the β5-β6 loop, relieving the steric clash with the R1 side-chain carboxypropyl group of aztreonam and ceftazidime. These results reveal worrying trends in the enhancement of substrate spectrum of class D β-lactamases but may also provide a map for β-lactam improvement.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.