Aldo/keto reductase family signatures

The aldo-keto reductase family [1,2] groups together a number of structurally and functionally related NADPH-dependent oxidoreductases as well as some other proteins. The proteins known to belong to this family are:

• Aldehyde reductase (EC 1.1.1.2).
• Aldose reductase (EC 1.1.1.21).
• 3-α-hydroxysteroid dehydrogenase (EC 1.1.1.50), which terminates androgen action by converting 5-α-dihydrotestosterone to 3-α- androstanediol.
• Prostaglandin F synthase (EC 1.1.1.188) which catalyzes the reduction of prostaglandins H2 and D2 to F2-α.
• D-sorbitol-6-phosphate dehydrogenase (EC 1.1.1.200) from apple.
• Morphine 6-dehydrogenase (EC 1.1.1.218) from Pseudomonas putida plasmid pMDH7.2 (gene morA).
• Chlordecone reductase (EC 1.1.1.225) which reduces the pesticide chlordecone (kepone) to the corresponding alcohol.
• 2,5-diketo-D-gluconic acid reductase (EC 1.1.1.274) which catalyzes the reduction of 2,5-diketogluconic acid to 2-keto-L-gulonic acid, a key intermediate in the production of ascorbic acid.
• NAD(P)H-dependent xylose reductase (EC 1.1.1.-) from the yeast Pichia stipitis. This enzyme reduces xylose into xylit.
• Trans-1,2-dihydrobenzene-1,2-diol dehydrogenase (EC 1.3.1.20).
• 3-oxo-5-β-steroid 4-dehydrogenase (EC 1.3.99.6) which catalyzes the reduction of delta(4)-3-oxosteroids.
• A soybean reductase, which co-acts with chalcone synthase in the formation of 4,2',4'-trihydroxychalcone.
• Frog eye lens rho crystallin.
• Yeast GCY protein, whose function is not known.
• Leishmania major P110/11E protein. P110/11E is a developmentally regulated protein whose abundance is markedly elevated in promastigotes compared with amastigotes. Its exact function is not yet known.
• Escherichia coli hypothetical protein yafB.
• Escherichia coli hypothetical protein yghE.
• Yeast hypothetical protein YBR149w.
• Yeast hypothetical protein YHR104w.
• Yeast hypothetical protein YJR096w.

These proteins have all about 300 amino acid residues. We derived 3 consensus patterns specific to this family of proteins. The first one is located in the N-terminal section of these proteins. The second pattern is located in the central section. The third pattern, located in the C-terminal, is centered on a lysine residue whose chemical modification, in aldose and aldehyde reductases, affect the catalytic efficiency.