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A Novel Mechanism for Azoreduction
- Source :
-
Journal of Molecular Biology . Jul2010, Vol. 400 Issue 1, p24-37. 14p. - Publication Year :
- 2010
-
Abstract
- 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. [Copyright &y& Elsevier]
Details
- Language :
- English
- ISSN :
- 00222836
- Volume :
- 400
- Issue :
- 1
- Database :
- Academic Search Index
- Journal :
- Journal of Molecular Biology
- Publication Type :
- Academic Journal
- Accession number :
- 51442897
- Full Text :
- https://doi.org/10.1016/j.jmb.2010.04.023