1w3r
From Proteopedia
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| - | [[Image:1w3r.jpg|left|200px]] | + | [[Image:1w3r.jpg|left|200px]] |
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| - | '''NIMA FROM D. RADIODURANS WITH METRONIDAZOLE AND PYRUVATE''' | + | {{Structure |
| + | |PDB= 1w3r |SIZE=350|CAPTION= <scene name='initialview01'>1w3r</scene>, resolution 1.90Å | ||
| + | |SITE= <scene name='pdbsite=AC1:2mn+Binding+Site+For+Chain+A'>AC1</scene> | ||
| + | |LIGAND= <scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=PYR:PYRUVIC+ACID'>PYR</scene> and <scene name='pdbligand=2MN:2-(2-METHYL-5-NITRO-1H-IMIDAZOL-1-YL)ETHANOL'>2MN</scene> | ||
| + | |ACTIVITY= | ||
| + | |GENE= | ||
| + | }} | ||
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| + | '''NIMA FROM D. RADIODURANS WITH METRONIDAZOLE AND PYRUVATE''' | ||
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==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1W3R is a [ | + | 1W3R is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Deinococcus_radiodurans Deinococcus radiodurans]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1W3R OCA]. |
==Reference== | ==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:[http:// | + | 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:[http://www.ncbi.nlm.nih.gov/pubmed/15492014 15492014] |
[[Category: Deinococcus radiodurans]] | [[Category: Deinococcus radiodurans]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
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[[Category: antibiotic resistance]] | [[Category: antibiotic resistance]] | ||
[[Category: catalytic mechanism]] | [[Category: catalytic mechanism]] | ||
| - | [[Category: deinococcus | + | [[Category: deinococcus radioduran]] |
[[Category: nim gene]] | [[Category: nim gene]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 14:51:44 2008'' |
Revision as of 12:51, 20 March 2008
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| , resolution 1.90Å | |||||||
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| Sites: | |||||||
| Ligands: | , and | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
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. 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
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