title: Structure of porphobilinogen deaminase reveals a flexible multidomain polymerase with a single catalytic site.
abstract: The three-domain structure of porphobilinogen deaminase, a key enzyme in the biosynthetic pathway of tetrapyrroles, has been defined by X-ray analysis at 1.9 A resolution. Two of the domains structurally resemble the transferrins and periplasmic binding proteins. The dipyrromethane cofactor is covalently linked to domain 3 but is bound by extensive salt-bridges and hydrogen-bonds within the cleft between domains 1 and 2, at a position corresponding to the binding sites for small-molecule ligands in the analogous proteins. The X-ray structure and results from site-directed mutagenesis provide evidence for a single catalytic site. Interdomain flexibility may aid elongation of the polypyrrole product in the active-site cleft of the enzyme.
authors.affiliation: Department of Crystallography, Birkbeck College, University of London, UK.
authors.forename: G V
authors.initials: GV
authors.lastname: Louie
authors.forename: P D
authors.initials: PD
authors.lastname: Brownlie
authors.forename: R
authors.initials: R
authors.lastname: Lambert
authors.forename: J B
authors.initials: JB
authors.lastname: Cooper
authors.forename: T L
authors.initials: TL
authors.lastname: Blundell
authors.forename: S P
authors.initials: SP
authors.lastname: Wood
authors.forename: M J
authors.initials: MJ
authors.lastname: Warren
authors.forename: S C
authors.initials: SC
authors.lastname: Woodcock
authors.forename: P M
authors.initials: PM
authors.lastname: Jordan
mesh_terms: D001665:Binding Sites; D003067:Coenzymes / Q000737:chemistry; D011163:Hydroxymethylbilane Synthase / Q000737:chemistry*; D008958:Models, Molecular; D015394:Molecular Structure; D011162:Porphobilinogen / Q000737:chemistry; D011487:Protein Conformation
chemical_list: D003067:Coenzymes; C056776:dipyrromethane cofactor; D011162:Porphobilinogen; D011163:Hydroxymethylbilane Synthase