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1w3r
From Proteopedia
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NIMA FROM D. RADIODURANS WITH METRONIDAZOLE AND PYRUVATE
Overview
5-Nitroimidazole-based antibiotics are compounds extensively used for, treating infections in humans and animals caused by several important, pathogens. They are administered as prodrugs, and their activation depends, upon an anaerobic 1-electron reduction of the nitro group by a reduction, pathway in the cells. Bacterial resistance toward these drugs is thought, to be caused by decreased drug uptake and/or an altered reduction, efficiency. One class of resistant strains, identified in Bacteroides, has, been shown to carry Nim genes (NimA, -B, -C, -D, and -E), which encode for, reductases that convert the nitro group on the antibiotic into a, non-bactericidal amine. In this paper, we have described the crystal, structure of NimA from Deinococcus radiodurans (drNimA) at 1.6 A, resolution. We have shown that drNimA is a homodimer in which each monomer, adopts a beta-barrel fold. We have identified the catalytically important, His-71 along with the cofactor pyruvate and antibiotic binding sites, all, of which are found at the monomer-monomer interface. We have reported, three additional crystal structures of drNimA, one in which the antibiotic, metronidazole is bound to the protein, one with pyruvate covalently bound, to His-71, and one with lactate covalently bound to His-71. Based on these, structures, a reaction mechanism has been proposed in which the 2-electron, reduction of the antibiotic prevents accumulation of the toxic nitro, radical. This mechanism suggests that Nim proteins form a new class of, reductases, conferring resistance against 5-nitroimidazole-based, antibiotics.
About this Structure
1W3R is a Single protein structure of sequence from Deinococcus radiodurans with ACT, PYR and 2MN as ligands. Structure known Active Site: AC1. Full crystallographic information is available from OCA.
Reference
Structural basis of 5-nitroimidazole antibiotic resistance: the crystal structure of NimA from Deinococcus radiodurans., Leiros HK, Kozielski-Stuhrmann S, Kapp U, Terradot L, Leonard GA, McSweeney SM, J Biol Chem. 2004 Dec 31;279(53):55840-9. Epub 2004 Oct 18. PMID:15492014
Page seeded by OCA on Mon Nov 5 13:25:59 2007
