title: Structure of Chlorobium vibrioforme 5-aminolaevulinic acid dehydratase complexed with a diacid inhibitor.
abstract: The structure of Chlorobium vibrioforme 5-aminolaevulinic acid dehydratase (ALAD) complexed with the irreversible inhibitor 4,7-dioxosebacic acid has been solved. The inhibitor binds by forming Schiff-base linkages with lysines 200 and 253 at the active site. The structure reported here provides a definition of the interactions made by both of the substrate molecules (A-side and P-side substrates) with the C. vibrioforme ALAD and is compared and contrasted with structures of the same inhibitor bound to Escherichia coli and yeast ALAD. The structure suggests why 4,7-dioxosebacic acid is a better inhibitor of the zinc-dependent ALADs than of the zinc-independent ALADs.
authors.affiliation: Bioscience Division, Los Alamos National Laboratory, NM 87545, USA. lcoates@lanl.gov
authors.forename: L
authors.initials: L
authors.lastname: Coates
authors.forename: G
authors.initials: G
authors.lastname: Beaven
authors.forename: P T
authors.initials: PT
authors.lastname: Erskine
authors.forename: Samuel I
authors.initials: SI
authors.lastname: Beale
authors.forename: S P
authors.initials: SP
authors.lastname: Wood
authors.forename: P M
authors.initials: PM
authors.lastname: Shoolingin-Jordan
authors.forename: J B
authors.initials: JB
authors.lastname: Cooper
mesh_terms: D001665:Binding Sites; D041883:Chlorobium / Q000201:enzymology; D003460:Crystallization; D018360:Crystallography, X-Ray; D003652:Decanoic Acids / Q000737:chemistry*; D004926:Escherichia coli / Q000201:enzymology; D008968:Molecular Conformation; D000623:Porphobilinogen Synthase / Q000037:antagonists & inhibitors* / Q000737:chemistry*; D012441:Saccharomyces cerevisiae / Q000201:enzymology; D012545:Schiff Bases / Q000737:chemistry; D015032:Zinc / Q000737:chemistry
chemical_list: C434703:4,7-dioxosebacic acid; D003652:Decanoic Acids; D012545:Schiff Bases; D000623:Porphobilinogen Synthase; D015032:Zinc