1jr2

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{{STRUCTURE_1jr2| PDB=1jr2 | SCENE= }}
{{STRUCTURE_1jr2| PDB=1jr2 | SCENE= }}
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'''Structure of Uroporphyrinogen III Synthase'''
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===Structure of Uroporphyrinogen III Synthase===
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==Overview==
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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.
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{{ABSTRACT_PUBMED_11689424}}
==Disease==
==Disease==
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[[Category: Heam biosynthesis]]
[[Category: Heam biosynthesis]]
[[Category: Heme biosynthesis]]
[[Category: Heme biosynthesis]]
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Revision as of 17:40, 1 July 2008

Image:1jr2.png

Template:STRUCTURE 1jr2

Contents

Structure of Uroporphyrinogen III Synthase

Template:ABSTRACT PUBMED 11689424

Disease

Known disease associated with this structure: Porphyria, congenital erythropoietic OMIM:[606938]

About this Structure

1JR2 is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

Reference

Crystal structure of human uroporphyrinogen III synthase., Mathews MA, Schubert HL, Whitby FG, Alexander KJ, Schadick K, Bergonia HA, Phillips JD, Hill CP, EMBO J. 2001 Nov 1;20(21):5832-9. PMID:11689424

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