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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.
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.
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