Aldo-keto reductase

The aldo-keto reductase family is a family of proteins that are subdivided into 16 categories; these include a number of related monomeric NADPH-dependent oxidoreductases, such as aldehyde reductase, aldose reductase, prostaglandin F synthase, xylose reductase, rho crystallin, and many others.[1]

Aldo/keto reductase family
Ribbon diagram of human aldose reductase in complex with NADP+, citrate, and IDD594, a small molecule inhibitor. From PDB: 1us0.


All possess a similar structure, with a beta-alpha-beta fold characteristic of nucleotide binding proteins.[2] 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.[3]

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.[4]


Some proteins of this family contain a potassium channel beta chain regulatory domain; these are reported to have oxidoreductase activity.[5]

See also


  1. Bohren KM, Bullock B, Wermuth B, Gabbay KH (June 1989). "The aldo-keto reductase superfamily. cDNAs and deduced amino acid sequences of human aldehyde and aldose reductases". J. Biol. Chem. 264 (16): 9547–51. PMID 2498333.
  2. Schade SZ, Early SL, Williams TR, Kézdy FJ, Heinrikson RL, Grimshaw CE, Doughty CC (March 1990). "Sequence analysis of bovine lens aldose reductase". J. Biol. Chem. 265 (7): 3628–35. PMID 2105951.
  3. Wilson DK, Bohren KM, Gabbay KH, Quiocho FA (July 1992). "An unlikely sugar substrate site in the 1.65 A structure of the human aldose reductase holoenzyme implicated in diabetic complications". Science. 257 (5066): 81–4. doi:10.1126/science.1621098. PMID 1621098.
  4. Borhani DW, Harter TM, Petrash JM (December 1992). "The crystal structure of the aldose reductase.NADPH binary complex". J. Biol. Chem. 267 (34): 24841–7. PMID 1447221.
  5. Gulbis JM, Zhou M, Mann S, MacKinnon R (July 2000). "Structure of the cytoplasmic beta subunit-T1 assembly of voltage-dependent K+ channels". Science. 289 (5476): 123–7. doi:10.1126/science.289.5476.123. PMID 10884227.
This article incorporates text from the public domain Pfam and InterPro: IPR001395
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