Structural highlights
4fsk is a 1 chain structure with sequence from Aspfl. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
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| Ligands: | ACE, AZI, NA |
| Related: | 3p9f, 3p9o |
| Gene: | uaZ, uox (ASPFL) |
| Activity: | Factor independent urate hydroxylase, with EC number 1.7.3.3 |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
[URIC_ASPFL] Catalyzes the oxidation of uric acid to 5-hydroxyisourate, which is further processed to form (S)-allantoin.
Publication Abstract from PubMed
BACKGROUND: Urate oxidase (EC 1.7.3.3 or UOX) catalyzes the conversion of uric acid and gaseous molecular oxygen to 5-hydroxyisourate and hydrogen peroxide, in the absence of cofactor or particular metal cation. The functional enzyme is a homo-tetramer with four active sites located at dimeric interfaces. RESULTS: The catalytic mechanism was investigated through a ternary complex formed between the enzyme, uric acid, and cyanide that stabilizes an intermediate state of the reaction. When uric acid is replaced by a competitive inhibitor, no complex with cyanide is formed. CONCLUSION: The X-ray structure of this compulsory ternary complex led to a number of mechanistic evidences that support a sequential mechanism in which the two reagents, dioxygen and a water molecule, process through a common site located 3.3 A above the mean plane of the ligand. This site is built by the side chains of Asn 254, and Thr 57, two conserved residues belonging to two different subunits of the homo-tetramer. The absence of a ternary complex between the enzyme, a competitive inhibitor, and cyanide suggests that cyanide inhibits the hydroxylation step of the reaction, after the initial formation of a hydroperoxyde type intermediate.
Structural analysis of urate oxidase in complex with its natural substrate inhibited by cyanide: mechanistic implications.,Gabison L, Prange T, Colloc'h N, El Hajji M, Castro B, Chiadmi M BMC Struct Biol. 2008 Jul 20;8:32. PMID:18638417[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Gabison L, Prange T, Colloc'h N, El Hajji M, Castro B, Chiadmi M. Structural analysis of urate oxidase in complex with its natural substrate inhibited by cyanide: mechanistic implications. BMC Struct Biol. 2008 Jul 20;8:32. PMID:18638417 doi:10.1186/1472-6807-8-32
