Aldo-keto reductase (AKR) superfamily: Genomics and annotation

<p>Abstract</p> <p>Aldo-keto reductases (<it>AKRs</it>) are phase I metabolising enzymes that catalyse the reduced nicotinamide adenine dinucleotide (phosphate) (NAD(P)H)-dependent reduction of carbonyl groups to yield primary and secondary alcohols on a wide range of s...

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Bibliographic Details
Main Authors: Mindnich Rebekka D, Penning Trevor M
Format: Article
Language:English
Published: BMC 2009-07-01
Series:Human Genomics
Subjects:
SNP
Online Access:http://www.humgenomics.com/content/3/4/362
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Summary:<p>Abstract</p> <p>Aldo-keto reductases (<it>AKRs</it>) are phase I metabolising enzymes that catalyse the reduced nicotinamide adenine dinucleotide (phosphate) (NAD(P)H)-dependent reduction of carbonyl groups to yield primary and secondary alcohols on a wide range of substrates, including aliphatic and aromatic aldehydes and ketones, ketoprostaglan-dins, ketosteroids and xenobiotics. In so doing they functionalise the carbonyl group for conjugation (phase II enzyme reactions). Although functionally diverse, <it>AKRs </it>form a protein superfamily based on their high sequence identity and common protein fold, the (α/(β)<sub>8</sub>-barrel structure. Well over 150 AKR enzymes, from diverse organisms, have been annotated so far and given systematic names according to a nomenclature that is based on multiple protein sequence alignment and degree of identity. Annotation of non-vertebrate <it>AKRs </it>at the National Center for Biotechnology Information or Vertebrate Genome Annotation (vega) database does not often include the systematic nomenclature name, so the most comprehensive overview of all annotated <it>AKRs </it>is found on the AKR website (<url>http://www.med.upenn.edu/akr/</url>). This site also hosts links to more detailed and specialised information (eg on crystal structures, gene expression and single nucleotide polymorphisms [SNPs]). The protein-based AKR nomenclature allows unambiguous identification of a given enzyme but does not reflect the wealth of genomic and transcriptomic variation that exists in the various databases. In this context, identification of putative new <it>AKRs </it>and their distinction from pseudogenes are challenging. This review provides a short summary of the characteristic features of AKR biochemistry and structure that have been reviewed in great detail elsewhere, and focuses mainly on nomenclature and database entries of human <it>AKRs </it>that so far have not been subject to systematic annotation. Recent developments in the annotation of SNP and transcript variance in <it>AKRs </it>are also summarised.</p>
ISSN:1479-7364