The high resolution crystal structure of rat liver AKR7A1: understanding the substrate specificites of the AKR7 family.
The structure of the rat liver aflatoxin dialdehyde reductase (AKR7A1) has been solved to 1.38 A resolution. The crystal structure reveals details of the ternary complex as one subunit of the dimer contains NADP+ and the inhibitor citrate. The underlying catalytic mechanism appears similar to other aldo-keto reductases (AKR), whilst the substrate-binding pocket contains several positively charged amino acids (Arg-231 and Arg-327) which distinguishes it from the well characterised AKR1 family of enzymes. These differences account for the substrate specificity for 4-carbon acid-aldehydes such as succinic semialdehyde (SSA) and 2-carboxybenzaldehyde, as well as for the idiosyncratic substrate aflatoxin B1 dialdehyde of this subfamily of enzymes. The AKR7 enzymes seem to be subdivided into two subgroups based on their sequence and kinetic properties. Modelling of the rat AKR7A4 highlights important structural differences localised within the active site of the two isoenzymes.
Kozma
Evelin
E
Department of Chemistry, University of Glasgow, G12 8QQ, Glasgow, UK.
Brown
Elaine
E
Ellis
Elizabeth M
EM
Lapthorn
Adrian J
AJ
D000449:Aldehyde Reductase / Q000737:chemistry* / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D002384:Catalysis; D018360:Crystallography, X-Ray; D008099:Liver / Q000201:enzymology*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011487:Protein Conformation; D051381:Rats; D017386:Sequence Homology, Amino Acid; D013379:Substrate Specificity
C442302:AKR7A1; D000449:Aldehyde Reductase