1w3o
From Proteopedia
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'''CRYSTAL STRUCTURE OF NIMA FROM D. RADIODURANS''' | '''CRYSTAL STRUCTURE OF NIMA FROM D. RADIODURANS''' | ||
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[[Category: Terradot, L.]] | [[Category: Terradot, L.]] | ||
[[Category: 5-nitroimidazole resistance]] | [[Category: 5-nitroimidazole resistance]] | ||
| - | [[Category: | + | [[Category: Antibiotic resistance]] |
| - | [[Category: | + | [[Category: Catalytic mechanism]] |
| - | [[Category: | + | [[Category: Deinococcus radioduran]] |
| - | [[Category: | + | [[Category: Nim gene]] |
| - | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 13:06:55 2008'' | |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | |
Revision as of 10:06, 3 May 2008
CRYSTAL STRUCTURE OF NIMA FROM D. RADIODURANS
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
1W3O is a Single protein structure of sequence from Deinococcus radiodurans. 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 Sat May 3 13:06:55 2008
