6lj0

From Proteopedia

Crystal structure of NDM-1 in complex with D-captopril derivative wss02122

Structural highlights

6lj0 is a 1 chain structure with sequence from Klebsiella pneumoniae. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 1.2Å
Ligands:	,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

BLAN1_KLEPN Confers resistance to many beta-lactam antibiotics, including some carbapenems. Does not confer resistance to the polymixin colistin or the fluoroquinolone ciprofloxacin.

Publication Abstract from PubMed

beta-lactam antibiotics have long been the mainstay for the treatment of bacterial infections. New Delhi metallo-beta-lactamase 1 (NDM-1) is able to hydrolyze nearly all beta-lactam antibiotics and even clinically used serine-beta-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.

Structure-guided optimization of D-captopril for discovery of potent NDM-1 inhibitors.,Ma G, Wang S, Wu K, Zhang W, Ahmad A, Hao Q, Lei X, Zhang H Bioorg Med Chem. 2020 Dec 3;29:115902. doi: 10.1016/j.bmc.2020.115902. PMID:33302045^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ 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. 2020 Dec 3;29:115902. doi: 10.1016/j.bmc.2020.115902. PMID:33302045 doi:http://dx.doi.org/10.1016/j.bmc.2020.115902