4e1v

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X-RAY Structure of the Uridine Phosphorylase from Salmonella Typhimurium in Complex with 5-Fluorouracil at 2.15 A ResolutionX-RAY Structure of the Uridine Phosphorylase from Salmonella Typhimurium in Complex with 5-Fluorouracil at 2.15 A Resolution

Structural highlights

4e1v is a 9 chain structure with sequence from Salmonella enterica subsp. enterica serovar Typhimurium str. LT2. This structure supersedes the now removed PDB entry 3nsr. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:, , ,
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[UDP_SALTY] Catalyzes the reversible phosphorylytic cleavage of uridine and deoxyuridine to uracil and ribose- or deoxyribose-1-phosphate. The produced molecules are then utilized as carbon and energy sources or in the rescue of pyrimidine bases for nucleotide synthesis (By similarity).

Publication Abstract from PubMed

Uridine phosphorylase (UPh), which is a key enzyme in the reutilization pathway of pyrimidine nucleoside metabolism, is a validated target for the treatment of infectious diseases and cancer. A detailed analysis of the interactions of UPh with the therapeutic ligand 5-fluorouracil (5-FUra) is important for the rational design of pharmacological inhibitors of these enzymes in prokaryotes and eukaryotes. Expanding on the preliminary analysis of the spatial organization of the active centre of UPh from the pathogenic bacterium Salmonella typhimurium (StUPh) in complex with 5-FUra [Lashkov et al. (2009), Acta Cryst. F65, 601-603], the X-ray structure of the StUPh-5-FUra complex was analysed at atomic resolution and an in silico model of the complex formed by the drug with UPh from Vibrio cholerae (VchUPh) was generated. These results should be considered in the design of selective inhibitors of UPhs from various species.

X-ray structure of Salmonella typhimurium uridine phosphorylase complexed with 5-fluorouracil and molecular modelling of the complex of 5-fluorouracil with uridine phosphorylase from Vibrio cholerae.,Lashkov AA, Sotnichenko SE, Prokofiev II, Gabdulkhakov AG, Agapov II, Shtil AA, Betzel C, Mironov AS, Mikhailov AM Acta Crystallogr D Biol Crystallogr. 2012 Aug;68(Pt 8):968-74. Epub 2012 Jul 17. PMID:22868762[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

See Also

References

  1. Lashkov AA, Sotnichenko SE, Prokofiev II, Gabdulkhakov AG, Agapov II, Shtil AA, Betzel C, Mironov AS, Mikhailov AM. X-ray structure of Salmonella typhimurium uridine phosphorylase complexed with 5-fluorouracil and molecular modelling of the complex of 5-fluorouracil with uridine phosphorylase from Vibrio cholerae. Acta Crystallogr D Biol Crystallogr. 2012 Aug;68(Pt 8):968-74. Epub 2012 Jul 17. PMID:22868762 doi:http://dx.doi.org/10.1107/S090744491201815X

4e1v, resolution 2.15Å

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