This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.
Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.
1w3r
From Proteopedia
| Line 1: | Line 1: | ||
[[Image:1w3r.jpg|left|200px]] | [[Image:1w3r.jpg|left|200px]] | ||
| - | + | <!-- | |
| - | + | The line below this paragraph, containing "STRUCTURE_1w3r", creates the "Structure Box" on the page. | |
| - | + | You may change the PDB parameter (which sets the PDB file loaded into the applet) | |
| - | + | or the SCENE parameter (which sets the initial scene displayed when the page is loaded), | |
| - | | | + | or leave the SCENE parameter empty for the default display. |
| - | | | + | --> |
| - | + | {{STRUCTURE_1w3r| PDB=1w3r | SCENE= }} | |
| - | + | ||
| - | + | ||
| - | }} | + | |
'''NIMA FROM D. RADIODURANS WITH METRONIDAZOLE AND PYRUVATE''' | '''NIMA FROM D. RADIODURANS WITH METRONIDAZOLE AND PYRUVATE''' | ||
| Line 32: | Line 29: | ||
[[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 13:06:59 2008'' | |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | |
Revision as of 10:06, 3 May 2008
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 Page seeded by OCA on Sat May 3 13:06:59 2008
