Crystal structure of protoporphyrinogen oxidase from Myxococcus xanthus and its complex with the inhibitor acifluorfen.
Protoporphyrinogen IX oxidase, a monotopic membrane protein, which catalyzes the oxidation of protoporphyrinogen IX to protoporphyrin IX in the heme/chlorophyll biosynthetic pathway, is distributed widely throughout nature. Here we present the structure of protoporphyrinogen IX oxidase from Myxococcus xanthus, an enzyme with similar catalytic properties to human protoporphyrinogen IX oxidase that also binds the common plant herbicide, acifluorfen. In the native structure, the planar porphyrinogen substrate is mimicked by a Tween 20 molecule, tracing three sides of the macrocycle. In contrast, acifluorfen does not mimic the planarity of the substrate but is accommodated by the shape of the binding pocket and held in place by electrostatic and aromatic interactions. A hydrophobic patch surrounded by positively charged residues suggests the position of the membrane anchor, differing from the one proposed for the tobacco mitochondrial protoporphyrinogen oxidase. Interestingly, there is a discrepancy between the dimerization state of the protein in solution and in the crystal. Conserved structural features are discussed in relation to a number of South African variegate porphyria-causing mutations in the human enzyme.
Corradi
Hazel R
HR
Department of Biology and Biochemistry, University of Bath, Bath BA2 7AY, United Kingdom.
Corrigall
Anne V
AV
Boix
Ester
E
Mohan
C Gopi
CG
Sturrock
Edward D
ED
Meissner
Peter N
PN
Acharya
K Ravi
KR
D018360:Crystallography, X-Ray; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D008958:Models, Molecular; D016941:Myxococcus xanthus / Q000737:chemistry*; D009579:Nitrobenzoates / Q000737:chemistry / Q000494:pharmacology*; D011487:Protein Conformation; D050768:Protoporphyrinogen Oxidase / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000302:isolation & purification
D004791:Enzyme Inhibitors; D009579:Nitrobenzoates; D050768:Protoporphyrinogen Oxidase; C018425:acifluorfen