<p>The aldo-keto reductase family includes a number of related monomeric NADPH-dependent oxidoreductases, such as aldehyde reductase, aldose reductase, prostaglandin F synthase, xylose reductase, rho crystallin, and many others [<cite idref="PUB00002548"/>]. All possess a similar structure, with a beta-alpha-beta fold characteristic of nucleotide binding proteins [<cite idref="PUB00002605"/>]. 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 [<cite idref="PUB00005156"/>].</p> <p>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 [<cite idref="PUB00002751"/>].</p><p> Some proteins of this entry contain a K+ ion channel beta chain regulatory domain; these are reported to have oxidoreductase activity [<cite idref="PUB00015049"/>]. </p>