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A novel mechanism for azoreduction.
- Source :
-
Journal of molecular biology [J Mol Biol] 2010 Jul 02; Vol. 400 (1), pp. 24-37. Date of Electronic Publication: 2010 Apr 24. - Publication Year :
- 2010
-
Abstract
- Azoreductases are important due to their ability to activate anti-inflammatory azo pro-drugs and to detoxify azo dyes. Three genes encoding azoreductases have been identified in Pseudomonas aeruginosa. We describe here a comparison of the three enzymes. The pure recombinant proteins each have a distinct substrate specificity profile against a range of azo substrates. Using the structure of P. aeruginosa azoreductase (paAzoR) 1 and the homology models of paAzoR2 and paAzoR3, we have identified residues important for substrate specificity. We have defined a novel flavin mononucleotide binding cradle, which is a recurrent motif in many flavodoxin-like proteins. A novel structure of paAzoR1 with the azo pro-drug balsalazide bound within the active site was determined by X-ray crystallography and demonstrates that the substrate is present in a hydrazone tautomer conformation. We propose that the structure with balsalazide bound represents an enzyme intermediate and, together with the flavin mononucleotide binding cradle, we propose a novel catalytic mechanism.<br /> (Copyright 2010 Elsevier Ltd. All rights reserved.)
- Subjects :
- Amino Acid Sequence
Binding Sites
Crystallography, X-Ray
Flavin Mononucleotide chemistry
Flavin Mononucleotide metabolism
Humans
Models, Molecular
Molecular Sequence Data
Molecular Structure
NADH, NADPH Oxidoreductases genetics
Nitroreductases
Oxidation-Reduction
Pseudomonas aeruginosa enzymology
Sequence Alignment
Substrate Specificity
Azo Compounds chemistry
NADH, NADPH Oxidoreductases chemistry
NADH, NADPH Oxidoreductases metabolism
Protein Conformation
Subjects
Details
- Language :
- English
- ISSN :
- 1089-8638
- Volume :
- 400
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Journal of molecular biology
- Publication Type :
- Academic Journal
- Accession number :
- 20417637
- Full Text :
- https://doi.org/10.1016/j.jmb.2010.04.023