Koonin E V, Tatusov R L
National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD 20894.
J Mol Biol. 1994 Nov 18;244(1):125-32. doi: 10.1006/jmbi.1994.1711.
Using an iterative approach to sequence database search that combines scanning with individual amino acid sequences and with alignment blocks, we show that bacterial haloacid dehalogenases (HADs) belong to a large superfamily of hydrolases with diverse substrate specificity. The superfamily also includes epoxide hydrolases, different types of phosphatases, and numerous uncharacterized proteins from eubacteria, eukaryotes, and Archaea. Nine putative proteins of the HAD superfamily with functions unknown, in addition to two known enzymes, were found in Escherichia coli alone, making it one of the largest groups of enzymes and indicating that a variety of hydrolytic enzyme activities remain to be described. Many of the proteins with known enzymatic activities in the HAD superfamily are involved in detoxification of xenobiotics or metabolic by-products. All the proteins in the superfamily contain three conserved sequence motifs. Along with the conservation of the predicted secondary structure, motifs I, II, and III include a conserved aspartic acid residue, a lysine, and a nucleophile, namely aspartic acid or serine, respectively. A specific role in the catalysis of the hydrolysis of carbon-halogen and other bonds is assigned to each of these residues.
我们采用迭代方法进行序列数据库搜索，该方法将单个氨基酸序列扫描与比对模块相结合，结果表明细菌卤代酸脱卤酶（HADs）属于一个水解酶超家族，其底物特异性多样。该超家族还包括环氧化物水解酶、不同类型的磷酸酶，以及来自真细菌、真核生物和古细菌的众多未鉴定蛋白质。仅在大肠杆菌中就发现了9种功能未知的HAD超家族假定蛋白，加上2种已知酶，这使其成为最大的酶类群之一，表明仍有多种水解酶活性有待描述。HAD超家族中许多具有已知酶活性的蛋白质参与了异源生物或代谢副产物的解毒过程。该超家族中的所有蛋白质都包含三个保守序列基序。除了预测二级结构的保守性外，基序I、II和III分别包含一个保守的天冬氨酸残基、一个赖氨酸和一个亲核试剂，即天冬氨酸或丝氨酸。这些残基在催化碳卤键及其他键的水解中各自发挥特定作用。
