Sequence and structure of epoxide hydrolases: a systematic analysis.
Epoxide hydrolases (EC 3.3.2.3) are ubiquitous enzymes that catalyze the hydrolysis of epoxides to the corresponding vicinal diols. More than 100 epoxide hydrolases (EH) have been identified or predicted, and 3 structures are available. Although they catalyze the same chemical reaction, sequence similarity is low. To identify conserved regions, all EHs were aligned. Phylogenetic analysis identified 12 homologous families, which were grouped into 2 major superfamilies: the microsomal EH superfamily, which includes the homologous families of Mammalian, Insect, Fungal, and Bacterial EHs, and the cytosolic EH superfamily, which includes Mammalian, Plant, and Bacterial EHs. Bacterial EHs show a high sequence diversity. Based on structure comparison of three known structures from Agrobacterium radiobacter AD1 (cytosolic EH), Aspergillus niger (microsomal EH), Mus musculus (cytosolic EH), and multisequence alignment and phylogenetic analysis of 95 EHs, the modular architecture of this enzyme family was analyzed. Although core and cap domain are highly conserved, the structural differences between the EHs are restricted to only two loops: the NC-loop connecting the core and the cap and the cap-loop, which is inserted into the cap domain. EHs were assigned to either of three clusters based on loop length. By using this classification, core and cap region of all EHs, NC-loops and cap-loops of 78% and 89% of all EHs, respectively, could be modeled. Representative models are available from the Lipase Engineering Database, http://www.led.uni-stuttgart.de.
Barth
Sandra
S
Institute of Technical Biochemistry, University of Stuttgart, Germany.
Fischer
Markus
M
Schmid
Rolf D
RD
Pleiss
Jürgen
J
D000595:Amino Acid Sequence; D000818:Animals; D004851:Epoxide Hydrolases / Q000737:chemistry* / Q000145:classification / Q000235:genetics; D008958:Models, Molecular; D010802:Phylogeny; D017433:Protein Structure, Secondary; D016415:Sequence Alignment; D040681:Structural Homology, Protein
D004851:Epoxide Hydrolases