Uroporphyrinogen III synthase

Uroporphyrinogen-III synthase
Uroporphyrinogen-III synthase monomer, Thermus thermophilus
Identifiers
EC no.	4.2.1.75
CAS no.	37340-55-9
Databases
IntEnz	IntEnz view
BRENDA	BRENDA entry
ExPASy	NiceZyme view
KEGG	KEGG entry
MetaCyc	metabolic pathway
PRIAM	profile
PDB structures	RCSB PDB PDBe PDBsum
Gene Ontology	AmiGO / QuickGO
Search PMC articles PubMed articles NCBI proteins

Uroporphyrinogen III synthase
Identifiers
Symbol	UROS
NCBI gene	7390
HGNC	12592
OMIM	606938
RefSeq	NM_000375
UniProt	P10746
Other data
EC number	4.2.1.75
Locus	Chr. 10 q25.2-26.3
Search for Structures Swiss-model Domains InterPro

Uroporphyrinogen-III synthase HemD
crystal structure of uroporphyrinogen iii synthase from an extremely thermophilic bacterium thermus thermophilus hb8 (wild type, native, form-2 crystal)
Identifiers
Symbol	HEM4
Pfam	PF02602
InterPro	IPR003754
SCOP2	1jr2 / SCOPe / SUPFAM
Available protein structures: Pfam   structures / ECOD   PDB RCSB PDB; PDBe; PDBj PDBsum structure summary

Uroporphyrinogen III synthase (EC 4.2.1.75) is an enzyme involved in the metabolism of the cyclic tetrapyrrole compound porphyrin. It is involved in the conversion of hydroxymethylbilane into uroporphyrinogen III. This enzyme catalyses the inversion of the final pyrrole unit (ring D) of the linear tetrapyrrole molecule, linking it to the first pyrrole unit (ring A), thereby generating a large macrocyclic structure, uroporphyrinogen III. ^[1] The enzyme folds into two alpha/beta domains connected by a beta-ladder, the active site being located between the two domains. ^[2]

Heme synthesis—note that some reactions occur in the cytoplasm and some in the mitochondrion (yellow)

Function

The enzyme catalyses the cyclisation reaction of hydroxymethylbilane into uroporphyrinogen III via a spiro intermediate which allows one of the pyrrole rings to convert its initial acetate to propionate configuration into a propionate-acetate one. ^{[3] [4]}

hydroxymethylbilane

 

 

H₂O

 

H₂O

 

uroporphyrinogen III

Pathology

A deficiency is associated with Gunther's disease, also known as congenital erythropoietic porphyria (CEP). This is an autosomal recessive inborn error of metabolism that results from the markedly deficient activity of uroporphyrinogen III synthase. ^[5]

References

1. Raux E, Schubert HL, Warren MJ (December 2000). "Biosynthesis of cobalamin (vitamin B12): a bacterial conundrum". Cell. Mol. Life Sci. 57 (13–14): 1880–93. doi:10.1007/PL00000670. PMC   11147154 . PMID   11215515. S2CID   583311.
2. Mathews MA, Schubert HL, Whitby FG, Alexander KJ, Schadick K, Bergonia HA, Phillips JD, Hill CP (November 2001). "Crystal structure of human uroporphyrinogen III synthase". EMBO J. 20 (21): 5832–9. doi:10.1093/emboj/20.21.5832. PMC   125291 . PMID   11689424.
3. Battersby, Alan R.; Fookes, Christopher J. R.; Matcham, George W.J.; McDonald, Edward (1980). "Biosynthesis of the pigments of life: formation of the macrocycle". Nature. 285 (5759): 17–21. Bibcode:1980Natur.285...17B. doi:10.1038/285017a0. PMID   6769048. S2CID   9070849.
4. Enzyme 4.2.1.75 at KEGG Pathway Database.
5. To-Figueras J, Badenas C, Mascaro JM, Madrigal I, Merino A, Bastida P, Lecha M, Herrero C (2007). "Study of the genotype-phenotype relationship in four cases of congenital erythropoietic porphyria". Blood Cells Mol. Dis. 38 (3): 242–6. doi:10.1016/j.bcmd.2006.12.001. PMID   17270473.

External links

• Uroporphyrinogen+III+synthase at the U.S. National Library of Medicine Medical Subject Headings (MeSH)

This article incorporates text from the public domain Pfam and InterPro: IPR003754