PTHR11732

ALDO/KETO REDUCTASE

PANTHER entry
Member databasePANTHER
PANTHER typefamily

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

4.The aldo-keto reductases (AKRs): Overview. Penning TM. Chem Biol Interact 234, 236-46, (2015). PMID: 25304492

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