Steve Ealick's Research Group
Streptococcus pyogenes Uridine Phosphorylase
Uridine phosphorylase (UP) is a key enzyme in the pyrimidine salvage pathway and is found in most prokaryotes and eukaryotes. All known UPs belong to the nucleoside phosphorylase I (NP-I) superfamily; however, mammalian UPs are dimers, while bacterial UPs, such as Streptococcus pyogenese UP, are hexamers comprised of a trimer of dimers. This structure adds to our extensive work on NP-I families including purine nucleoside phosphorylase (bPNP, hPNP, EcPNP, TvPNP), methylthioadenosine phosphorylase (SsMTAP, SsMTAPII and hMTAP), adenosine 5´-monophosphate nucleosidase (AMN) and other uridine phosphorylases (bUP, EcUP and StUP) and 5´-methylthioadenosine/S-adenosylhomocysteine nucleosidase (MTAN).
The SpUP protomer adopts an α/β fold that is very similar to those of the other NP-I enzymes.
|The quaternary structure is hexameric, as are other bacterial UPs, with the trimer of dimers obvious in the structure at the right. Each protomer has an active site; however, the active sites are located at the dimer interface and have residues from each member of the dimer pair.|
The active site of SpUP, shows the bound uracil and ribose 1-phosphate that were isolated under the crystallization conditions.
Tran TH, Christoffersen S, Allan PW, Parker WB, Piskur J, Serra I, Terreni M, and Ealick SE. The Crystal Structure of Streptococcus pyogenes Uridine Phosphorylase Reveals a Distinct Subfamily of Nucleoside Phosphorylases. Biochemistry 50:6549–6558. (2011).