Structure of porphobilinogen deaminase reveals a flexible multidomain polymerase with a single catalytic site.
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.
Louie
G V
GV
Department of Crystallography, Birkbeck College, University of London, UK.
Brownlie
P D
PD
Lambert
R
R
Cooper
J B
JB
Blundell
T L
TL
Wood
S P
SP
Warren
M J
MJ
Woodcock
S C
SC
Jordan
P M
PM
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
D003067:Coenzymes; C056776:dipyrromethane cofactor; D011162:Porphobilinogen; D011163:Hydroxymethylbilane Synthase