6LJ8

Crystal structure of NDM-1 in complex with D-captopril derivative wss04134

Summary for 6LJ8

• Entry DOI: 10.2210/pdb6lj8/pdb
• Related: 5ZJ2 6LIP 6LIZ 6LJ0 6LJ1 6LJ2 6LJ4 6LJ5 6LJ6 6LJ7
• Descriptor: Metallo-beta-lactamase type 2, 2-[1-[(2S)-2-methyl-3-sulfanyl-propanoyl]piperidin-4-yl]ethanoic acid, 1,2-ETHANEDIOL, ... (5 entities in total)
• Functional Keywords: ndm-1, metallo-beta-lactamase, antibiotic resistent, inhibitor, thio compounds, antibiotic, hydrolase
• Biological source: Klebsiella pneumoniae
• Total number of polymer chains: 1
• Total formula weight: 26194.18

Authors

Zhang, H.,Ma, G. (deposition date: 2019-12-13, release date: 2020-12-16, Last modification date: 2023-11-22)

Primary citation

Ma, G.,Wang, S.,Wu, K.,Zhang, W.,Ahmad, A.,Hao, Q.,Lei, X.,Zhang, H.
Structure-guided optimization of D-captopril for discovery of potent NDM-1 inhibitors.
Bioorg.Med.Chem., 29:115902-115902, 2020

PubMed Abstract: β-lactam antibiotics have long been the mainstay for the treatment of bacterial infections. New Delhi metallo-β-lactamase 1 (NDM-1) is able to hydrolyze nearly all β-lactam antibiotics and even clinically used serine-β-lactamase inhibitors. The wide and rapid spreading of NDM-1 gene among pathogenic bacteria has attracted extensive attention, therefore high potency NDM-1 inhibitors are urgently needed. Here we report a series of structure-guided design of D-captopril derivatives that can inhibit the activity of NDM-1 in vitro and at cellular levels. Structural comparison indicates the mechanisms of inhibition enhancement and provides insights for further inhibitor optimization.

PubMed: 33302045
DOI: 10.1016/j.bmc.2020.115902

Experimental method

X-RAY DIFFRACTION (1.4 Å)