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The crystal structure of rat liver AKR7A1: a dimeric member of the Aldo-Keto reductase superfamily

Kozma, E. and Brown, E. and Ellis, E. and Lapthorn, A. (2002) The crystal structure of rat liver AKR7A1: a dimeric member of the Aldo-Keto reductase superfamily. Journal of Biological Chemistry, 277 (18). pp. 16285-16293. ISSN 0021-9258

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Abstract

The structure of the rat liver aflatoxin dialdehyde reductase (AKR7A1) has been solved to 1.38î.. resolution. Although it shares a similar a/b barrel structure with other members of the aldo-keto reductase superfamily, AKR7A1 is the first dimeric member to be crystallised. The crystal structure also reveals details of the ternary complex as one subunit of the dimer contains NADP+ and the inhibitor citrate. Although the underlying catalytic mechanism appears similar to other aldo-keto reductases, the substrate-binding pocket contains several charged amino acids (Arg-231 and Arg-327) that distinguish it from previously characterised aldo-keto reductases with respect to size and charge. These differences account for the substrate specificity for 4-carbon acid-aldehydes such as succinic semialdehyde and 2-carboxybenzaldehyde, as well as for the idiosyncratic substrate aflatoxin B1 dialdehyde of this subfamily of enzymes. Structural differences between the AKR7A1 ternary complex and apo-enzyme reveal a significant hinged movement of the enzyme involving not only the loops of the structure, but also parts of the a/b barrel most intimately involved in cofactor binding.

Item type: Article
ID code: 2548
Keywords: biological chemistry, rat liver, cofactor binding, Electronic computers. Computer science, Chemistry, Biochemistry, Cell Biology, Molecular Biology
Subjects: Science > Mathematics > Electronic computers. Computer science
Science > Chemistry
Department: Faculty of Science > Strathclyde Institute of Pharmacy and Biomedical Sciences
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Depositing user: Strathprints Administrator
Date Deposited: 15 Feb 2007
Last modified: 04 Sep 2014 11:04
URI: http://strathprints.strath.ac.uk/id/eprint/2548

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