1R3S

Uroporphyrinogen Decarboxylase single mutant D86G in complex with coproporphyrinogen-I

Summary for 1R3S

• Entry DOI: 10.2210/pdb1r3s/pdb
• Related: 1R3Q 1R3R 1R3T 1R3V 1R3W 1R3Y 1URO
• Descriptor: Uroporphyrinogen Decarboxylase, COPROPORPHYRINOGEN I (3 entities in total)
• Functional Keywords: uroporphyrinogen decarboxylase coproporphyrinogen; x-ray crystallography, lyase
• Biological source: Homo sapiens (human)
• Cellular location: Cytoplasm: P06132
• Total number of polymer chains: 1
• Total formula weight: 41434.49

Authors

Phillips, J.D.,Whitby, F.G.,Kushner, J.P.,Hill, C.P. (deposition date: 2003-10-03, release date: 2003-12-09, Last modification date: 2023-08-23)

Primary citation

Phillips, J.D.,Whitby, F.G.,Kushner, J.P.,Hill, C.P.
Structural basis for tetrapyrrole coordination by uroporphyrinogen decarboxylase
Embo J., 22:6225-6233, 2003

PubMed Abstract: 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.

PubMed: 14633982
DOI: 10.1093/emboj/cdg606

Experimental method

X-RAY DIFFRACTION (1.65 Å)