title: Catalytic mechanism and substrate selectivity of aldo-keto reductases: insights from structure-function studies of Candida tenuis xylose reductase.
abstract: Aldo-keto reductases (AKRs) constitute a large protein superfamily of mainly NAD(P)-dependent oxidoreductases involved in carbonyl metabolism. Catalysis is promoted by a conserved tetrad of active site residues (Tyr, Lys, Asp and His). Recent results of structure-function relationship studies for xylose reductase (AKR2B5) require an update of the proposed catalytic mechanism. Electrostatic stabilization by the epsilon-NH3+ group of Lys is a key source of catalytic power of xylose reductase. A molecular-level analysis of the substrate binding pocket of xylose reductase provides a case of how a very broadly specific AKR achieves the requisite selectivity for its physiological substrate and could serve as the basis for the design of novel reductases with improved specificities for biocatalytic applications.
authors.affiliation: Institute of Biotechnology and Biochemical Engineering, and Research Centre Applied Biocatalysis, Graz University of Technology, Graz, Austria.
authors.forename: Regina
authors.initials: R
authors.lastname: Kratzer
authors.forename: David K
authors.initials: DK
authors.lastname: Wilson
authors.forename: Bernd
authors.initials: B
authors.lastname: Nidetzky
mesh_terms: D000429:Alcohol Oxidoreductases / Q000737:chemistry* / Q000378:metabolism; D000449:Aldehyde Reductase / Q000737:chemistry* / Q000502:physiology; D000074408:Aldo-Keto Reductases; D002175:Candida / Q000201:enzymology*; D002384:Catalysis; D018360:Crystallography, X-Ray; D005656:Fungal Proteins / Q000737:chemistry*; D008956:Models, Chemical; D008958:Models, Molecular; D011485:Protein Binding; D055672:Static Electricity; D013329:Structure-Activity Relationship; D013379:Substrate Specificity; D014994:Xylose / Q000737:chemistry
chemical_list: D005656:Fungal Proteins; D014994:Xylose; D000429:Alcohol Oxidoreductases; D000074408:Aldo-Keto Reductases; D000449:Aldehyde Reductase