Aldo-keto reductase

Function

Aldo-keto reductase (AKR) is a protein family which contains enzymes that reduce carbonyl substrates like sugar aldehyde, keto-steroid, keto-prostaglandin, retinal, quinones and lipid peroxidation by-products to primary alcohol^[1]. AKR uses NADP as a cofactor. AKRs contain a conserved catalytic tetrad consisting of Tyr, Asp, Lys and His.

• AKR1B10 reduces aliphatic and aromatic aldehydes. It is expressed in adrenal gland, small intestines and colon.
  
• AKRB14 is involved in synthesis of prostaglandin F and detoxification of products of lipid peroxidation.
  
• AKR1D1 is responsible for the catalysis of 5-β-reduction of bile acid intermediates and steroid hormones carrying a δ(4)-3-one structure.
  

Disease

Mutations in AKR1D1 cause a form of bile acid deficiency which can be fatal in newborns^[2].

Structural highlights

The active site of AKR1B10 contains the cofactor NADP and a polyfluorinated inhibitor. Tyr and His are part of the enzyme catalytic tetrad^[3].

3D structures of aldo-keto reductase

Updated on 28-December-2016

See Hydroxysteroid dehydrogenase 20-alpha HSD

See Hydroxysteroid dehydrogenase 3-alpha HSD

See Prostaglandin F synthase

See Hydroxysteroid dehydrogenase 17-alpha HSD

References

1. ↑ Penning TM. The aldo-keto reductases (AKRs): Overview. Chem Biol Interact. 2015 Jun 5;234:236-46. doi: 10.1016/j.cbi.2014.09.024. Epub, 2014 Oct 7. PMID:25304492 doi:http://dx.doi.org/10.1016/j.cbi.2014.09.024
2. ↑ Drury JE, Mindnich R, Penning TM. Characterization of disease-related 5beta-reductase (AKR1D1) mutations reveals their potential to cause bile acid deficiency. J Biol Chem. 2010 Aug 6;285(32):24529-37. doi: 10.1074/jbc.M110.127779. Epub 2010, Jun 3. PMID:20522910 doi:http://dx.doi.org/10.1074/jbc.M110.127779
3. ↑ Cousido-Siah A, Ruiz FX, Mitschler A, Porte S, de Lera AR, Martin MJ, Manzanaro S, de la Fuente JA, Terwesten F, Betz M, Klebe G, Farres J, Pares X, Podjarny A. Identification of a novel polyfluorinated compound as a lead to inhibit the human enzymes aldose reductase and AKR1B10: structure determination of both ternary complexes and implications for drug design. Acta Crystallogr D Biol Crystallogr. 2014 Mar;70(Pt 3):889-903. doi:, 10.1107/S1399004713033452. Epub 2014 Feb 27. PMID:24598757 doi:http://dx.doi.org/10.1107/S1399004713033452