1r3w
Uroporphyrinogen Decarboxylase Y164F mutant in complex with coproporphyrinogen-III
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OverviewOverview
Uroporphyrinogen decarboxylase (URO-D), an essential enzyme that functions, in the heme biosynthetic pathway, catalyzes decarboxylation of all four, acetate groups of uroporphyrinogen to form coproporphyrinogen. Here we, report crystal structures of URO-D in complex with the I and III isomer, coproporphyrinogen products. Crystallization required use of a novel, enzymatic approach to generate the highly oxygen-sensitive porphyrinogen, substrate in situ. The tetrapyrrole product adopts a domed conformation, that lies against a collar of conserved hydrophobic residues and allows, formation of hydrogen bonding interactions between a carboxylate oxygen, atom of the invariant Asp86 residue and the pyrrole NH groups. Structural, and biochemical analyses of URO-D proteins mutated at Asp86 support the, conclusion that this residue makes important contributions to binding and, likely promotes catalysis by stabilizing a positive charge on a reaction, intermediate. The central coordination geometry of Asp86 allows the, initial substrates and the various partially decarboxylated intermediates, to be bound with equivalent activating interactions, and thereby explains, how all four of the substrate acetate groups can be decarboxylated at the, same catalytic center.
DiseaseDisease
Known diseases associated with this structure: Porphyria cutanea tarda OMIM:[176100], Porphyria, hepatoerythropoietic OMIM:[176100]
About this StructureAbout this Structure
1R3W is a Single protein structure of sequence from Homo sapiens with CP3 as ligand. Active as Uroporphyrinogen decarboxylase, with EC number 4.1.1.37 Full crystallographic information is available from OCA.
ReferenceReference
Structural basis for tetrapyrrole coordination by uroporphyrinogen decarboxylase., Phillips JD, Whitby FG, Kushner JP, Hill CP, EMBO J. 2003 Dec 1;22(23):6225-33. PMID:14633982
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