1URO

UROPORPHYRINOGEN DECARBOXYLASE

Summary for 1URO

• Entry DOI: 10.2210/pdb1uro/pdb
• Descriptor: PROTEIN (UROPORPHYRINOGEN DECARBOXYLASE), BETA-MERCAPTOETHANOL (3 entities in total)
• Functional Keywords: decarboxylase, alpha-8-beta-8 barrel, heme biosynthesis, porphyrin, uroporphyrinogen, lyase
• Biological source: Homo sapiens (human)
• Cellular location: Cytoplasm: P06132
• Total number of polymer chains: 1
• Total formula weight: 40909.90

Authors

Whitby, F.G.,Phillips, J.D.,Kushner, J.P.,Hill, C.P. (deposition date: 1998-08-21, release date: 1998-08-26, Last modification date: 2024-02-14)

Primary citation

Whitby, F.G.,Phillips, J.D.,Kushner, J.P.,Hill, C.P.
Crystal structure of human uroporphyrinogen decarboxylase.
EMBO J., 17:2463-2471, 1998

PubMed Abstract: Uroporphyrinogen decarboxylase (URO-D) catalyzes the fifth step in the heme biosynthetic pathway, converting uroporphyrinogen to coproporphyrinogen by decarboxylating the four acetate side chains of the substrate. This activity is essential in all organisms, and subnormal activity of URO-D leads to the most common form of porphyria in humans, porphyria cutanea tarda (PCT). We have determined the crystal structure of recombinant human URO-D at 1.60 A resolution. The 40.8 kDa protein is comprised of a single domain containing a (beta/alpha)8-barrel with a deep active site cleft formed by loops at the C-terminal ends of the barrel strands. Many conserved residues cluster at this cleft, including the invariant side chains of Arg37, Arg41 and His339, which probably function in substrate binding, and Asp86, Tyr164 and Ser219, which may function in either binding or catalysis. URO-D is a dimer in solution (Kd = 0.1 microM), and this dimer also appears to be formed in the crystal. Assembly of the dimer juxtaposes the active site clefts of the monomers, suggesting a functionally important interaction between the catalytic centers.

PubMed: 9564029
DOI: 10.1093/emboj/17.9.2463

Experimental method

X-RAY DIFFRACTION (1.8 Å)