Aldo-keto reductase family 1 member C

Definition

This entry represents aldo-keto reductase family 1 member C (AKR1C), including aldehyde reductase (ALR) AKR1C1-5 from mammals. The AKR1C family belongs to the aldo-keto reductase (AKR) family. ALR, also known as aldehyde reductase, or ALDR1, catalyses the NADPH-dependent reduction of a variety of aromatic and aliphatic aldehydes to their corresponding alcohols. In vitro substrates include succinic semialdehyde, 4-nitrobenzaldehyde, 1,2-naphthoquinone, methylglyoxal, and D-glucuronic acid [[cite:PMID:11306097], [cite:PMID:7552731]]. 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 [[cite:PMID:2498333], [cite:PMID:25304492]]. 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 PMID:25304492. 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 PMID:1621098. They catalyse an ordered bi bi kinetic mechanism in which NAD(P)H cofactor binds first and leaves last PMID:25304492. 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 PMID:1447221.

5 human proteins with this domain

Each is a reviewed human protein in the Seroatlas serome and a potential autoantibody target; this domain groups them into one antibody-relevant category. Every entry links to its own record.

Download CSV (5 proteins: gene, accession, name)

• AKR1C1
• AKR1C2
• AKR1C3
• AKR1C4
• AKR1C8