1JR2

Structure of Uroporphyrinogen III Synthase

Summary for 1JR2

• Entry DOI: 10.2210/pdb1jr2/pdb
• Descriptor: UROPORPHYRINOGEN-III SYNTHASE (2 entities in total)
• Functional Keywords: heme biosynthesis, heam biosynthesis, lyase
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 2
• Total formula weight: 62378.73

Authors

Mathews, M.A.,Schubert, H.L.,Whitby, F.G.,Alexander, K.J.,Schadick, K.,Bergonia, H.A.,Phillips, J.D.,Hill, C.P. (deposition date: 2001-08-10, release date: 2001-11-07, Last modification date: 2024-02-07)

Primary citation

Mathews, M.A.,Schubert, H.L.,Whitby, F.G.,Alexander, K.J.,Schadick, K.,Bergonia, H.A.,Phillips, J.D.,Hill, C.P.
Crystal structure of human uroporphyrinogen III synthase.
EMBO J., 20:5832-5839, 2001

PubMed Abstract: Uroporphyrinogen III synthase, U3S, the fourth enzyme in the porphyrin biosynthetic pathway, catalyzes cyclization of the linear tetrapyrrole, hydroxymethylbilane, to the macrocyclic uroporphyrino gen III, which is used in several different pathways to form heme, siroheme, chlorophyll, F(430) and vitamin B(12). U3S activity is essential in all organisms, and decreased activity in humans leads to the autosomal recessive disorder congenital erythropoetic porphyria. We have determined the crystal structure of recombinant human U3S at 1.85 A resolution. The protein folds into two alpha/beta domains connected by a beta-ladder. The active site appears to be located between the domains, and variations in relative domain positions observed between crystallographically independent molecules indicates the presence of flexibility that may be important in the catalytic cycle. Possible mechanisms of catalysis were probed by mutating each of the four invariant residues in the protein that have titratable side chains. Additionally, six other highly conserved and titratable side chains were also mutated. In no case, however, did one of these mutations abolish enzyme activity, suggesting that the mechanism does not require acid/base catalysis.

PubMed: 11689424
DOI: 10.1093/emboj/20.21.5832

Experimental method

X-RAY DIFFRACTION (1.84 Å)