Aldo-keto reductase

Structure

All possess a similar structure, with a beta-alpha-beta fold characteristic of nucleotide binding proteins. The fold comprises a parallel beta-8/alpha-8-barrel, which contains a novel NADP-binding motif. The binding site is located in a large, deep, elliptical pocket in the C-terminal end of the beta sheet, the substrate being bound in an extended conformation. The hydrophobic nature of the pocket favours aromatic and apolar substrates over highly polar ones.

Binding of the NADPH coenzyme causes a massive conformational change, reorienting a loop, effectively locking the coenzyme in place. This binding is more similar to FAD- than to NAD(P)-binding oxidoreductases.

Examples

Some proteins of this family contain a potassium channel beta chain regulatory domain; these are reported to have oxidoreductase activity.

References

References

1. (June 1989). "The aldo-keto reductase superfamily. cDNAs and deduced amino acid sequences of human aldehyde and aldose reductases". J. Biol. Chem..
2. (March 1990). "Sequence analysis of bovine lens aldose reductase". J. Biol. Chem..
3. (July 1992). "An unlikely sugar substrate site in the 1.65 A structure of the human aldose reductase holoenzyme implicated in diabetic complications". Science.
4. (December 1992). "The crystal structure of the aldose reductase.NADPH binary complex". J. Biol. Chem..
5. (July 2000). "Structure of the cytoplasmic beta subunit-T1 assembly of voltage-dependent K+ channels". Science.