Target intelligence / Profile preview

New Delhi metallo-beta-lactamase 1 (NDM-1)

Target
NDM-1
Molecular classification
Enzyme, Metallo-beta-lactamase (MBL), subclass B1, Oxidoreductase/metallo-hydrolase superfamily, Beta-lactamase (class B1)
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Overview

New Delhi metallo-beta-lactamase 1 (NDM-1) is a zinc-dependent hydrolase enzyme found primarily in Gram-negative bacteria, most notably in Enterobacteriaceae such as Klebsiella pneumoniae. NDM-1 hydrolyzes a broad spectrum of beta-lactam antibiotics—including penicillins, cephalosporins, and carbapenems—by cleaving the beta-lactam ring, thereby rendering these antibiotics ineffective. Its active site contains two zinc ions coordinated by conserved residues and is distinguished by flexibility, allowing accommodation of diverse substrates. Discovered in 2009, NDM-1 has become a major cause of multidrug-resistant infections worldwide, mostly due to the mobility of its encoding blaNDM-1 gene on plasmids. Development of effective inhibitors is challenged by its broad substrate tolerance and structural adaptability. NDM-1's presence is a serious global health threat due to its role in the spread of antibiotic resistance.

Other names
NDM-1New Delhi metallo-beta-lactamase-1Metallo-beta-lactamase NDM-1NDM enzyme
02

Mechanism of action

Enzymatic hydrolysis of beta-lactam ring (zinc ion activates water/hydroxide that cleaves the beta-lactam ring, inactivating antibiotics); Inhibitors block active site, usually by chelating zinc or mimicking substrate.

03

Biological functions

Hydrolysis of beta-lactam antibioticsBacterial antibiotic resistance mechanismOther (mediating resistance via hydrolytic breakdown of antibiotics)
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Disease associations

Infection (major clinical target in multidrug-resistant bacterial infections)Other (spreads in Gram-negative Enterobacteriaceae, critical in hospital- and community-acquired infections)
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Safety considerations

Therapeutic challenge: extreme breadth of substrate specificity makes development of inhibitors difficultSpread of resistance gene (blaNDM-1) via plasmids (contributes to rapid global dissemination of resistance)Lack of clinically effective inhibitorsPotential for pan-resistant infections
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Interacting drugs

Beta-lactam antibiotics (substrates: penicillins, cephalosporins, carbapenems)

2 more in the full profile.

07

Biomarkers

Presence of blaNDM-1 gene in pathogens (can be used as a biomarker for resistance)NDM-1 protein expression/activity (indicative of drug resistance)

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