Member database | PANTHER |
PANTHER type | family |
Description Imported from IPR020471
In general, the aldo-keto reductase (AKR) protein superfamily members reduce carbonyl substrates such as: sugar aldehydes, keto-steroids, keto-prostaglandins, retinals, quinones, and lipid peroxidation by-products
[3, 4]. However, there are some exceptions, such as the reduction of steroid double bonds catalysed by AKR1D enzymes (5beta-reductases); and the oxidation of proximate carcinogen trans-dihydrodiol polycyclic aromatic hydrocarbons; while the beta-subunits of potassium gated ion channels (AKR6 family) control Kv channel opening
[4].
Structurally, they contain an (α/β)8-barrel motif, display large loops at the back of the barrel which govern substrate specificity, and have a conserved cofactor binding domain. The binding site is located in a large, deep, elliptical pocket in the C-terminal end of the β-sheet, the substrate being bound in an extended conformation. The hydrophobic nature of the pocket favours aromatic and apolar substrates over highly polar ones
[1]. They catalyse an ordered bi bi kinetic mechanism in which NAD(P)H cofactor binds first and leaves last
[4]. 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
[2].
References Imported from IPR020471
1.An unlikely sugar substrate site in the 1.65 A structure of the human aldose reductase holoenzyme implicated in diabetic complications. Wilson DK, Bohren KM, Gabbay KH, Quiocho FA. Science 257, 81-4, (1992). View articlePMID: 1621098
2.The crystal structure of the aldose reductase.NADPH binary complex. Borhani DW, Harter TM, Petrash JM. J. Biol. Chem. 267, 24841-7, (1992). View articlePMID: 1447221
3.The aldo-keto reductase superfamily. cDNAs and deduced amino acid sequences of human aldehyde and aldose reductases. Bohren KM, Bullock B, Wermuth B, Gabbay KH. J. Biol. Chem. 264, 9547-51, (1989). View articlePMID: 2498333