A NEW NOMENCLATURE FOR THE ALDO-KETO REDUCTASE SUPERFAMILY

The aldo-keto reductases (AKRs) represent a growing oxidoreductase sup erfamily. Forty proteins have been identified and characterized as AKR s, and an additional fourteen genes may encode proteins related to the superfamily. Found in eukaryotes and prokaryotes, the AKRs metabolize a wide range of substrates, including aliphatic aldehydes, monosaccha rides, steroids, prostaglandins, and xenobiotics. This broad substrate specificity has caused problems in naming these proteins. Enzymes cap able of these reactions have been referred to as aldehyde reductase (A LR1), aldose reductase (ALR2), and carbonyl reductase (ALR3); however, ALR3 is not a member of the AKR superfamily. Also, some AKRs have mul tiple names based upon substrate specificity. For example, human 3 alp ha-hydroxysteroid dehydrogenase (3 alpha-HSD) type I is also known as dihydrodiol dehydrogenase 4 and chlordecone reductase. To address thes e issues, we propose a new nomenclature system for the AKR superfamily based on amino acid sequence identities. Cluster analysis of the AKRs shows seven distinct families at the 40% amino acid identity level. T he largest family (AKR1) contains the aldose reductases, aldehyde redu ctases, and HSDs. Other families include the prokaryotic AKRs, the pla nt chalcone reductases, the Shaker channels, and the ethoxyquin-induci ble aflatoxin B-1 aldehyde reductase. At the level of 60% amino acid i dentity, subfamilies are discernible. For example, the AKR1 family inc ludes five subfamilies: (A) aldehyde reductases (mammalian); (B) aldos e reductases; (C) HSDs; (D) Delta(4)-3-ketosteroid 5 beta-reductases; and (E) aldehyde reductases (plane). This cluster analysis forms the b asis for our nomenclature system. Recommendations for naming an aldo-k eto reductase include the root symbol ''AKR,'' an Arabic number design ating the family, a letter indicating the subfamily when multiple subf amilies exist, and an Arabic numeral representing the unique protein s equence. For example, human aldehyde reductase would be assigned as AK R1A1. Our nomenclature is both systematic and expandable, thereby allo wing assignment of consistent designations for newly identified member s of the superfamily. (C) 1997 Elsevier Science Inc.