1JR2

Structure of Uroporphyrinogen III Synthase

1JR2 の概要

• エントリーDOI: 10.2210/pdb1jr2/pdb
• 分子名称: UROPORPHYRINOGEN-III SYNTHASE (2 entities in total)
• 機能のキーワード: heme biosynthesis, heam biosynthesis, lyase
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 62378.73

構造登録者

Mathews, M.A.,Schubert, H.L.,Whitby, F.G.,Alexander, K.J.,Schadick, K.,Bergonia, H.A.,Phillips, J.D.,Hill, C.P. (登録日: 2001-08-10, 公開日: 2001-11-07, 最終更新日: 2024-02-07)

主引用文献

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

実験手法

X-RAY DIFFRACTION (1.84 Å)