The aldo-keto reductase superfamily homepage

The aldo-keto reductase superfamily homepage
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DOI:
10.1016/s0009-2797(02)00193-x
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发表时间:
2003-02-01
影响因子:
5.1
通讯作者:
Penning, TM
Penning, TM
中科院分区:
医学2区
文献类型:
--
作者:
Hyndman, D;Bauman, DR;Penning, TM

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醛酮还原酶(AKRs)是在多种天然和外来底物上进行氧化还原的三个酶超家族之一。AKR超家族的系统命名于1996年通过,并于2000年9月更新(访问www.med.upenn.edu/akr)。调查人员一直在勤奋地向该网站提交功能蛋白质序列。随着新成员的加入,该超家族包含114个在原核生物和真核生物中表达的蛋白质,分布在14个家族(AKR1-AKR14)。AKR1家族包括醛糖还原酶、醛还原酶、羟基类固醇脱氢酶和类固醇5β-还原酶,是最大的。其他感兴趣的家族包括AKR6和AKR7,AKR6包括钾通道β亚基,AKR7是黄曲霉毒素醛还原酶。两个新的家族包括AKR13(酵母醛糖还原酶)和AKR14(大肠杆菌醛还原酶)。许多AKR及其与配体的络合物的晶体结构可在PDB中获得,并可通过网站访问。每个结构都具有超家族的(α/β)(8)桶基序,保守的辅因子结合位点和催化四分体,以及定义底物特异性的可变环结构。虽然大多数AKR是长度约为320个氨基酸的单体蛋白,但AKR2、AKR6和AKR7家族也可能形成多聚体。为了扩展命名法以适应多聚体,我们建议列出组成和化学计量。例如,AKR7A1:AKR7A4(1:3)将指定所示组成的四聚体。目前的命名得到了人类基因组计划(Hugo)的认可,该网站提供了到基因组信息的链接,包括染色体定位、基因边界、人类EST和SNPs等。(C)2002爱思唯尔科学爱尔兰有限公司。保留所有权利。
The aldo-keto reductases (AKRs) are one of the three enzyme superfamilies that perform oxidoreduction on a wide variety of natural and foreign substrates. A systematic nomenclature for the AKR superfamily was adopted in 1996 and was updated in September 2000 (visit www.med.upenn.edu/akr). Investigators have been diligent in submitting sequences of functional proteins to the Web site. With the new additions, the superfamily contains 114 proteins expressed in prokaryotes and eukaryotes that are distributed over 14 families (AKR1-AKR14). The AKR1 family contains the aldose reductases, the aldehyde reductases, the hydroxysteroid dehydrogenases and steroid 5beta-reductases, and is the largest. Other families of interest include AKR6, which includes potassium channel beta-subunits, and AKR7 the aflatoxin aldehyde reductases. Two new families include AKR13 (yeast aldose reductase) and AKR14 (Escherichia coli aldehyde reductase). Crystal structures of many AKRs and their complexes with ligands are available in the PDB and accessible through the Web site. Each structure has the characteristic (alpha/beta)(8)-barrel motif of the superfamily, a conserved cofactor binding site and a catalytic tetrad, and variable loop structures that define substrate specificity. Although the majority of AKRs are monomeric proteins of about 320 amino acids in length, the AKR2, AKR6 and AKR7 family may form multimers. To expand the nomenclature to accommodate multimers, we recommend that the composition and stoichiometry be listed. For example, AKR7A1:AKR7A4 (1:3) would designate a tetramer of the composition indicated. The current nomenclature is recognized by the Human Genome Project (HUGO) and the Web site provides a link to genomic information including chromosomal localization, gene boundaries, human ESTs and SNPs and much more. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.