Computer analysis of bacterial haloacid dehalogenases defines a large superfamily of hydrolases with diverse specificity. Application of an iterative approach to database search.
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.
National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD 20894.
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Koonin
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Tatusov
D000595:Amino Acid Sequence; D001419:Bacteria / Q000201:enzymology*; D001665:Binding Sites; D001673:Biodegradation, Environmental; D005075:Biological Evolution; D002264:Carboxylic Acids / Q000378:metabolism; D003201:Computers; D017124:Conserved Sequence; D016208:Databases, Factual; D004851:Epoxide Hydrolases / Q000235:genetics; D006846:Hydrocarbons, Halogenated / Q000378:metabolism; D006867:Hydrolases / Q000145:classification* / Q000235:genetics*; D008954:Models, Biological; D008956:Models, Chemical; D008969:Molecular Sequence Data; D005810:Multigene Family; D016415:Sequence Alignment / Q000379:methods*; D017386:Sequence Homology, Amino Acid; D013223:Statistics as Topic; D013379:Substrate Specificity; D015262:Xenobiotics / Q000378:metabolism
D002264:Carboxylic Acids; D006846:Hydrocarbons, Halogenated; D015262:Xenobiotics; D006867:Hydrolases; D004851:Epoxide Hydrolases; C034507:2-haloacid dehalogenase