ArticleAntimicrobial agents and chemotherapy2016
Role of Non-Active-Site Residue Trp-93 in the Function and Stability of New Delhi Metallo-β-Lactamase 1.
Article in Antimicrobial agents and chemotherapy, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed.
- Computer-aided screening of marine fungal metabolites as potential inhibitors of new Delhi metallo-beta-lactamase-1.Scientific reports · 2025Article
- Active site loops of membrane-anchored metallo-β-lactamases from environmental bacteria determine cephalosporinase activity.Antimicrobial agents and chemotherapy · 2025Article
- Antibiotic Stewardship Program in a General Hospital in Abu Dhabi, UAE: Preparedness for the COVID-19 Pandemic.Cureus · 2024Article
- Origin of Antibiotics and Antibiotic Resistance, and Their Impacts on Drug Development: A Narrative Review.Pharmaceuticals (Basel, Switzerland) · 2023Review
- Identification of a Potential Inhibitor (MCULE-8777613195-0-12) of New Delhi Metallo-β-Lactamase-1 (NDM-1) Using In Silico and In Vitro Approaches.Molecules (Basel, Switzerland) · 2022Article
- Risedronate and Methotrexate Are High-Affinity Inhibitors of New Delhi Metallo-β-Lactamase-1 (NDM-1): A Drug Repurposing Approach.Molecules (Basel, Switzerland) · 2022Article
- Enzyme Inhibitors: The Best Strategy to Tackle Superbug NDM-1 and Its Variants.International journal of molecular sciences · 2021Review
- Metallo-β-lactamases in the Age of Multidrug Resistance: From Structure and Mechanism to Evolution, Dissemination, and Inhibitor Design.Chemical reviews · 2021Review
- Evaluation of the roles of hydrophobic residues in the N-terminal region of archaeal trehalase in its folding.Applied microbiology and biotechnology · 2021Article
- Benzimidazole and Benzoxazole Zinc Chelators as Inhibitors of Metallo-β-Lactamase NDM-1.ChemMedChem · 2021Article
- Application Fields, Positions, and Bioinformatic Mining of Non-active Sites: A Mini-Review.Frontiers in chemistry · 2021Review
- A mechanistic approach to prove the efficacy of combination therapy against New Delhi metallo-β-lactamases producing bacterial strain: a molecular and biochemical approach.European journal of medical research · 2020Article
- Biogenesis of ZnO nanoparticles usingRSC advances · 2019Article
- High-Throughput Virtual Screening, Molecular Dynamics Simulation, and Enzyme Kinetics Identified ZINC84525623 as a Potential Inhibitor of NDM-1.International journal of molecular sciences · 2019Article
- Significant role of Asn-247 and Arg-64 residues in close proximity of the active site in maintaining the catalytic function of CTX-M-15 type β-lactamase.RSC advances · 2019Article
- Biosynthesized Silver Nanoparticle (AgNP) FromFrontiers in microbiology · 2019Article
- The mechanism of NDM-1-catalyzed carbapenem hydrolysis is distinct from that of penicillin or cephalosporin hydrolysis.Nature communications · 2017Article
- Structure, Genetics and Worldwide Spread of New Delhi Metallo-β-lactamase (NDM): a threat to public health.BMC microbiology · 2017Review
- Onion Peel Ethylacetate Fraction and Its Derived Constituent Quercetin 4'-Frontiers in microbiology · 2017Article
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Abstract
New Delhi metallo-β-lactamase-1 (NDM-1) is expressed by various members of Enterobacteriaceae as a defense mechanism to hydrolyze β-lactam antibiotics. Despite various studies showing the significance of active-site residues in the catalytic mechanism, there is a paucity of reports addressing the role of non-active-site residues in the structure and function of NDM-1. In this study, we investigated the significance of non-active-site residue Trp-93 in the structure and function of NDM-1. We cloned blaNDM-1 from an Enterobacter cloacae clinical strain (EC-15) and introduced the mutation of Trp-93 to Ala (yielding the Trp93Ala mutant) by PCR-based site-directed mutagenesis. Proteins were expressed and purified to homogeneity by affinity chromatography. The MICs of the Trp93Ala mutant were reduced 4- to 8-fold for ampicillin, cefotaxime, ceftazidime, cefoxitin, imipenem, and meropenem. The poor hydrolytic activity of the Trp93Ala mutant was also reflected by its reduced catalytic efficiency. The overall catalytic efficiency of the Trp93Ala mutant was reduced by 40 to 55% (the Km was reduced, while the kcat was similar to that of wild-type NDM-1 [wtNDM-1]). Heat-induced denaturation showed that the ΔGD (o) and Tm of Trp93Ala mutant were reduced by 1.8 kcal/mol and 4.8°C, respectively. Far-UV circular dichroism (CD) analysis showed that the α-helical content of the Trp93Ala mutant was reduced by 2.9%. The decrease in stability and catalytic efficiency of the Trp93Ala mutant was due to the loss of two hydrogen bonds with Ser-63 and Val-73 and hydrophobic interactions with Leu-65, Val-73, Gln-123, and Asp-124. The study provided insight into the role of non-active-site amino acid residues in the hydrolytic mechanism of NDM-1.
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