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 sythesis 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].

3D structures of aldo-keto reductase

Updated on 28-December-2016 {{#tree:id=OrganizedByTopic|openlevels=0|

• AKR1B1

• • 2j8t – hAKR1B1 + NADP - human
    

• AKR1B4

• • 4hbq – AKR1B4 – blood fluke
    

• AKR1B10

• • 4xzm – hAKR1B10 + NADP
    
  • 4xzn – hAKR1B10 (mutant) + NADP
    
  • 4jih, 4jii, 4i5x – hAKR1B10 + NADP + inhibitor
    
  • 4ga8, 4gab, 1zua, 5liy, 5lik, 5liu, 5liw, 5lix, 4xzl, 4wev, 4icc – hAKR1B10 (mutant) + NADP + inhibitor
    
  • 4gq0 – hAKR1B10 + NADP + caffeic acid ester
    

• AKR1B14

• • 3o3r – rAKR1B14 + NADP - rat
    
  • 3qkz – rAKR1B14 (mutant) + NADP
    

• AKR1C1

See Hydroxysteroid dehydrogenase 20-alpha HSD

• AKR1C2 or 3-alpha hydroxysteroid dehydrogenase

See Hydroxysteroid dehydrogenase 3-alpha HSD

• AKR1C3

See Prostaglandin F synthase

• AKR1C4

• • 2fvl – hAKR1C4 + NADP
    

• AKR1C21 or 17-alpha hydroxysteroid dehydrogenase

See Hydroxysteroid dehydrogenase 17-alpha HSD

• AKR1D1 or 3-oxo-5-beta-steroid 4-dehydrogenase

• • 3caq, 3buv, 3bv7 – hAKR1D1 + NADP
    
  • 3dop – hAKR1D1 + NADP + 5-beta-dehydrotestosterone
    
  • 3uzy – hAKR1D1 (mutant) + NADP + 5-beta-dehydrotestosterone
    
  • 3bur – hAKR1D1 (mutant) + NADP + testosterone
    
  • 3uzz – hAKR1D1 (mutant) + NADP + 5-delta-androstenedione
    
  • 3cas – hAKR1D1 + NADP + 4-androstenedione
    
  • 3g1r – hAKR1D1 + NADP + finasteride
    
  • 3cav – hAKR1D1 + NADP + 5-beta-pregnan-3,20-dione
    
  • 3cmf – hAKR1D1 + NADP + cortisone
    
  • 3cot – hAKR1D1 + NADP + progesterone
    

• AKR2E4

• • 3wcz – AKR2E4 + NADP – silk moth
    

• AKR4C8

• • 3h7r – AtAKR4C8 + NADP – Arabidopsis thaliana
    

• AKR4C9

• • 3h7u – AtAKR4C8 + NADP
    

• AKR7A1 or aflatoxin aldehyde reductase

• • 1gve – AKR7A1 + NADP – rat
    

• AKR11A or IOLS protein

• • 1pyf – BsAKR11A – Bacillus subtilis
    
  • 1pz0 – BsAKR11A + NADP
    

• AKR11B or general stress protein 69

• • 1pz1 – BsAKR11B + NADP
    

• AKR11B4

• • 3n2t – AKR11B4 – Gluconobacter oxydans
    

• AKR11C1

• • 1ynp – BhAKR11C1 – Bacillus halodurans
    
  • 1ynq – BhAKR11C1 + NADP
    

• AKR14A1

• • 4ast – EcAKR14A1 – Escherichia coli
    
  • 4aub – EcAKR14A1 + NADP
    

• AKR

• • 4xap – RmAKR – Rhizobium meliloti
    
  • 5c7h – RmAKR + NADP
    
  • 4xk2 – AKR – Polaromonas
    
  • 4wgh – AKR (mutant) + NADP – Klebsiella pneumoniae
    
  • 3n6q – EcAKR
    
  • 3o0k – AKR – Brucella melitensis
    
  • 2wzt – MsAKR – Mycobacterium smegmatis
    
  • 2wzm – MsAKR + ligand
    

]]

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