The crystal structure of rat liver AKR7A1. A dimeric member of the aldo-keto reductase superfamily.
The structure of the rat liver aflatoxin dialdehyde reductase (AKR7A1) has been solved to 1.38-A resolution. Although it shares a similar alpha/beta-barrel structure with other members of the aldo-keto reductase superfamily, AKR7A1 is the first dimeric member to be crystallized. 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 characterized 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 B(1) dialdehyde of this subfamily of enzymes. Structural differences between the AKR7A1 ternary complex and apoenzyme reveal a significant hinged movement of the enzyme involving not only the loops of the structure but also parts of the alpha/beta-barrel most intimately involved in cofactor binding.
Kozma
Evelin
E
Department of Chemistry, University of Glasgow, Glasgow G12 8QQ, United Kingdom.
Brown
Elaine
E
Ellis
Elizabeth M
EM
Lapthorn
Adrian J
AJ
D000449:Aldehyde Reductase / Q000737:chemistry* / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D002384:Catalysis; D018360:Crystallography, X-Ray; D019281:Dimerization; D008099:Liver / Q000201:enzymology*; D008958:Models, Molecular; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D021122:Protein Subunits; D051381:Rats; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D013379:Substrate Specificity
D021122:Protein Subunits; D011994:Recombinant Proteins; C442302:AKR7A1; D000449:Aldehyde Reductase