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| | {{STRUCTURE_1ylr| PDB=1ylr | SCENE= }} | | {{STRUCTURE_1ylr| PDB=1ylr | SCENE= }} |
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| - | '''The structure of E.coli nitroreductase with bound acetate, crystal form 1'''
| + | ===The structure of E.coli nitroreductase with bound acetate, crystal form 1=== |
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| - | ==Overview==
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| - | The antibiotics nitrofurazone and nitrofurantoin are used in the treatment of genitourinary infections and as topical antibacterial agents. Their action is dependent upon activation by bacterial nitroreductase flavoproteins, including the Escherichia coli nitroreductase (NTR). Here we show that the products of reduction of these antibiotics by NTR are the hydroxylamine derivatives. We show that the reduction of nitrosoaromatics is enzyme-catalyzed, with a specificity constant approximately 10,000-fold greater than that of the starting nitro compounds. This suggests that the reduction of nitro groups proceeds through two successive, enzyme-mediated reactions and explains why the nitroso intermediates are not observed. The global reaction rate for nitrofurazone determined in this study is over 10-fold higher than that previously reported, suggesting that the enzyme is much more active toward nitroaromatics than previously estimated. Surprisingly, in the crystal structure of the oxidized NTR-nitrofurazone complex, nitrofurazone is oriented with its amide group, rather than the nitro group to be reduced, positioned over the reactive N5 of the FMN cofactor. Free acetate, which acts as a competitive inhibitor with respect to NADH, binds in a similar orientation. We infer that the orientation of bound nitrofurazone depends upon the redox state of the enzyme. We propose that the charge distribution on the FMN rings, which alters upon reduction, is an important determinant of substrate binding and reactivity in flavoproteins with broad substrate specificity.
| + | The line below this paragraph, {{ABSTRACT_PUBMED_15684426}}, adds the Publication Abstract to the page |
| | + | (as it appears on PubMed at http://www.pubmed.gov), where 15684426 is the PubMed ID number. |
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| | + | {{ABSTRACT_PUBMED_15684426}} |
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| | ==About this Structure== | | ==About this Structure== |
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| | [[Category: Wrighton, C J.]] | | [[Category: Wrighton, C J.]] |
| | [[Category: Oxidoreductase]] | | [[Category: Oxidoreductase]] |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 16:29:08 2008'' | + | |
| | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 29 06:40:58 2008'' |
Revision as of 03:41, 29 July 2008
Template:STRUCTURE 1ylr
The structure of E.coli nitroreductase with bound acetate, crystal form 1
Template:ABSTRACT PUBMED 15684426
About this Structure
1YLR is a Single protein structure of sequence from Escherichia coli. Full crystallographic information is available from OCA.
Reference
Structural and mechanistic studies of Escherichia coli nitroreductase with the antibiotic nitrofurazone. Reversed binding orientations in different redox states of the enzyme., Race PR, Lovering AL, Green RM, Ossor A, White SA, Searle PF, Wrighton CJ, Hyde EI, J Biol Chem. 2005 Apr 8;280(14):13256-64. Epub 2005 Jan 31. PMID:15684426
Page seeded by OCA on Tue Jul 29 06:40:58 2008
