Taxonomic distribution of proteins containing PYNP_C domains

The tree below includes only several representative species and genera. The complete taxonomic breakdown of all proteins containing PYNP_C domains can be accessed here. Click the counts or percentage values to display the corresponding proteins.

The crystal structure of pyrimidine nucleoside phosphorylase in a closedconformation.

Pugmire MJ, Ealick SE
Structure. 1998; 6: 1467-79

BACKGROUND: Pyrimidine nucleoside phosphorylase (PYNP) catalyzes thereversible phosphorolysis of pyrimidines in the nucleotide synthesissalvage pathway. In lower organisms (e.g. Bacillus stearothermophilus)PYNP accepts both thymidine and uridine, whereas in mammalian and otherhigher organisms it is specific for thymidine (designated thymidinephosphorylase, TP). PYNP shares 40% sequence similarity (and presumablysignificant structural similarity) with human TP, which has beenimplicated as a growth factor in tumor angiogenesis. It is thought that TPundergoes a major conformational change upon substrate binding thatconsequently produces an active conformation. RESULTS: The crystalstructure of PYNP from B. stearothermophilus with the substrate analogpseudouridine in its active site has been solved to 2.1 A resolution. Thisstructure confirms the similarity of PYNP to TP and supports the idea of aclosed active conformation, which is the result of rigid body movement ofthe alpha and alpha/beta domains. The active-site cleft, where thepyrimidine and phosphate substrates bind, is between the two domains. Thestructure reveals an asymmetric dimer in which one subunit is fully closedand the other is only partially closed. CONCLUSIONS: The closedconformation of PYNP serves as a good model to better understand thedomain movement and overall function of TP. Active-site residues areconfirmed and a possible mechanism for substrate binding and subsequentdomain movement is suggested. Potent inhibitors of TP might havesignificant therapeutic value in various chemotherapeutic strategies, andthe structure of PYNP should provide valuable insight into the rationaldesign of such inhibitors.

Three-dimensional structure of thymidine phosphorylase from Escherichiacoli at 2.8 A resolution.

Walter MR, Cook WJ, Cole LB, Short SA, Koszalka GW, Krenitsky TA, Ealick SE
J Biol Chem. 1990; 265: 14016-22

The three-dimensional structure of thymidine phosphorylase fromEscherichia coli has been determined at 2.8 A resolution usingmultiple-isomorphous-replacement techniques. The amino acid sequencededuced from the deoA DNA sequence is also reported. Thymidinephosphorylase exists in the crystal as an S-shaped dimer in which thesubunits are related by a crystallographic 2-fold axis. Each subunit iscomposed of a small alpha-helical domain of six helices and a largealpha/beta domain. The alpha/beta domain includes a six-stranded mixedbeta-sheet and a four-stranded antiparallel beta-sheet. The active sitehas been identified by difference Fourier analyses of the binding ofthymine and thymidine and lies in a cavity between the small and largedomains. The central beta-sheet is splayed open to accommodate a putativephosphate-binding site which is probably occupied by a sulfate ion in thecrystal.