Summary
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. | |||||||||||
| Identifiers | |||||||||||
| Symbol | Aldo_ket_red | ||||||||||
| Pfam | PF00248 | ||||||||||
| InterPro | IPR001395 | ||||||||||
| PROSITE | PDOC00061 | ||||||||||
| SCOP2 | 1ads / SCOPe / SUPFAM | ||||||||||
| CDD | cd06660 | ||||||||||
| |||||||||||
Structure edit
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]
Examples edit
Some proteins of this family contain a potassium channel beta chain regulatory domain; these are reported to have oxidoreductase activity.[5]
See also edit
References edit
- ^ 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. doi:10.1016/S0021-9258(18)60566-6. PMID 2498333.
- ^ 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. doi:10.1016/S0021-9258(19)39639-5. PMID 2105951.
- ^ 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.
- ^ 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. doi:10.2210/pdb1abn/pdb. PMID 1447221.
- ^ 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. Bibcode:2000Sci...289..123G. doi:10.1126/science.289.5476.123. PMID 10884227.
