title: The crystal structure of HpcE, a bifunctional decarboxylase/isomerase with a multifunctional fold.
abstract: The structure of the bifunctional enzyme HpcE (OPET decarboxylase/HHDD isomerase) from Escherichia coli shows that the protein consists of highly similar N and C terminal halves. Sequence matches suggest that this fold is widespread among different species, including man. Many of these homologues are uncharacterized but apparently connected with the metabolism of aromatic compounds. The domain shows similar topology to the C terminal domain of fumarylacetoacetate hydrolase (FAH), a functionally related enzyme, despite lacking significant overall sequence similarity. HpcE is known to catalyze two rather different reactions, and comparisons with FAH allow some tentative conclusions to be drawn about the active sites. Key mutations within the active site apparently allow enzymes with this fold to carry out a variety chemical processes.
authors.affiliation: Protein Design Laboratory, Yokohama City University, Suehiro 1-7-29, Kanagawa 230-0045, Japan. jtame@tsurumi.yokohama-cu.ac.jp
authors.forename: Jeremy R H
authors.initials: JR
authors.lastname: Tame
authors.forename: Keiichi
authors.initials: K
authors.lastname: Namba
authors.forename: Eleanor J
authors.initials: EJ
authors.lastname: Dodson
authors.forename: David I
authors.initials: DI
authors.lastname: Roper
mesh_terms: D000595:Amino Acid Sequence; D019748:Carbon-Carbon Double Bond Isomerases / Q000737:chemistry* / Q000378:metabolism; D002262:Carboxy-Lyases / Q000737:chemistry* / Q000378:metabolism; D003460:Crystallization; D018360:Crystallography, X-Ray; D004926:Escherichia coli / Q000201:enzymology*; D007535:Isomerases / Q000737:chemistry; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009097:Multienzyme Complexes / Q000737:chemistry* / Q000378:metabolism; D017434:Protein Structure, Tertiary; D017386:Sequence Homology, Amino Acid
chemical_list: D009097:Multienzyme Complexes; D002262:Carboxy-Lyases; C031940:5-oxopent-3-ene-1,2,5-tricarboxylate decarboxylase; D007535:Isomerases; C084023:2-hydroxyhepta-2,4-diene-1,7-dioate isomerase; D019748:Carbon-Carbon Double Bond Isomerases