ArticleAntimicrobial agents and chemotherapy2014
Molecular mechanisms of substrate recognition and specificity of New Delhi metallo-β-lactamase.
Article in Antimicrobial agents and chemotherapy, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed.
- The global epidemiology and treatment of metallo-β-lactamase-producing gram-negative pathogens.JAC-antimicrobial resistance · 2026Review
- Contributions of β-lactamase substrate specificity and outer membrane permeability to the antibiotic sheltering of β-lactam-susceptible bacteria.RSC chemical biology · 2025Article
- Article
- Pharmacophore-Based Study: An In Silico Perspective for the Identification of Potential New Delhi Metallo-β-lactamase-1 (NDM-1) Inhibitors.Pharmaceuticals (Basel, Switzerland) · 2024Article
- Current Strategy for Targeting Metallo-β-Lactamase with Metal-Ion-Binding Inhibitors.Molecules (Basel, Switzerland) · 2024Review
- Design, synthesis and antibacterial activity evaluation of ebselen derivatives in NDM-1 producing bacteria.RSC medicinal chemistry · 2024Article
- Involvement of the non-active site Residues in the Catalytic Activity of NDM-4 Metallo beta-lactamase.The protein journal · 2023Article
- Specific Amino Acid Substitutions in OXA-51-TypeInternational journal of molecular sciences · 2022Article
- Enzyme Inhibitors: The Best Strategy to Tackle Superbug NDM-1 and Its Variants.International journal of molecular sciences · 2021Review
- Identification of a Novel Metallo-β-Lactamase, VAM-1, in a Foodborne Vibrio alginolyticus Isolate from China.Antimicrobial agents and chemotherapy · 2021Article
- Metallo-β-lactamases in the Age of Multidrug Resistance: From Structure and Mechanism to Evolution, Dissemination, and Inhibitor Design.Chemical reviews · 2021Review
- Identifying novel β-lactamase substrate activity throughMicrobial genomics · 2021Article
- Structural and biochemical characterization of the environmental MBLs MYO-1, ECV-1 and SHD-1.The Journal of antimicrobial chemotherapy · 2020Article
- Elusive structural changes of New Delhi metallo-β-lactamase revealed by ultraviolet photodissociation mass spectrometry.Chemical science · 2020Article
- Metallo-β-Lactamase Inhibitors Inspired on Snapshots from the Catalytic Mechanism.Biomolecules · 2020Review
- A Kinetic Study of the Replacement by Site Saturation Mutagenesis of Residue 119 in NDM-1 Metallo-β-Lactamase.Antimicrobial agents and chemotherapy · 2018Article
- Structural Insights into TMB-1 and the Role of Residues 119 and 228 in Substrate and Inhibitor Binding.Antimicrobial agents and chemotherapy · 2017Article
- Molecular Basis of Substrate Recognition and Product Release by the Klebsiella pneumoniae Carbapenemase (KPC-2).Journal of medicinal chemistry · 2017Article
- Ethyl 3-oxo-2-(2,5-dioxopyrrolidin-3-yl)butanoate Derivatives: Anthelmintic and Cytotoxic Potentials, Antimicrobial, and Docking Studies.Frontiers in chemistry · 2017Article
- Crystal Structure of Escherichia coli originated MCR-1, a phosphoethanolamine transferase for Colistin Resistance.Scientific reports · 2016Article
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Abstract
Carbapenems are one of the last lines of defense for Gram-negative pathogens, such as members of the Enterobacteriaceae. Despite the fact that most carbapenems are resistant to extended-spectrum β-lactamase (ESBL), emerging metallo-β-lactamases (MBLs), including New Delhi metallo-β-lactamase 1 (NDM-1), that can hydrolyze carbapenems have become prevalent and are frequently associated with the so-called "superbugs," for which treatments are extremely limited. Crystallographic study sheds light on the modes of antibiotic binding to NDM-1, yet the mechanisms governing substrate recognition and specificity are largely unclear. This study provides a connection between crystallographic study and the functional significance of NDM-1, with an emphasis on the substrate specificity and catalysis of various β-lactams. L1 loop residues L59, V67, and W87 were important for the activity of NDM-1, most likely through maintaining the partial folding of the L1 loop or active site conformation through hydrophobic interaction with the R groups of β-lactams or the β-lactam ring. Substitution of alanine for L59 showed greater reduction of MICs to ampicillin and selected cephalosporins, whereas substitutions of alanine for V67 had more impact on the MICs of carbapenems. K224 and N233 on the L3 loop played important roles in the recognition of substrate and contributed to substrate hydrolysis. These data together with the structure comparison of the B1 and B2 subclasses of MBLs revealed that the broad substrate specificity of NDM-1 could be due to the ability of its wide active site cavity to accommodate a wide range of β-lactams. This study provides insights into the development of efficient inhibitors for NDM-1 and offers an efficient tactic with which to study the substrate specificities of other β-lactamases.
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