1sq6

Structural highlights

Function

PNPH_PLAF7 As part of the purine salvage pathway, catalyzes the phosphorolytic breakdown of the N-glycosidic bond in the beta-(deoxy)ribonucleoside molecules, with the formation of the corresponding free purine bases and pentose-1-phosphate (PubMed:18957439, PubMed:14982926, PubMed:16131758, PubMed:19575810, PubMed:24416224, PubMed:29440412). Preferentially acts on inosine and guanosine, and to a lesser extent on 2'-deoxyguanosine and guanosine (PubMed:14982926, PubMed:16131758, PubMed:19575810). Also catalyzes the phosphorylation of S-methyl-5'-thioinosine (MTI) to hypoxanthine; MTI is produced by adenosine deaminase (ADA)-mediated breakdown of S-methyl-5'-thioadenosine (MTA), a major by-product of polyamine biosynthesis (PubMed:18957439, PubMed:14982926, PubMed:24416224). Generates hypoxanthine from both the purine salvage pathway and from polyamine metabolism which is required for nucleic acids synthesis (PubMed:18957439, PubMed:14982926, PubMed:24416224). Has no activity towards adenosine (By similarity).[UniProtKB:Q8T9Z7]^{[1] [2] [3] [4] [5] [6]}

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

References

1. ↑ Shi W, Ting LM, Kicska GA, Lewandowicz A, Tyler PC, Evans GB, Furneaux RH, Kim K, Almo SC, Schramm VL. Plasmodium falciparum purine nucleoside phosphorylase: crystal structures, immucillin inhibitors, and dual catalytic function. J Biol Chem. 2004 Apr 30;279(18):18103-6. Epub 2004 Feb 23. PMID:14982926 doi:10.1074/jbc.C400068200
2. ↑ Schnick C, Robien MA, Brzozowski AM, Dodson EJ, Murshudov GN, Anderson L, Luft JR, Mehlin C, Hol WG, Brannigan JA, Wilkinson AJ. Structures of Plasmodium falciparum purine nucleoside phosphorylase complexed with sulfate and its natural substrate inosine. Acta Crystallogr D Biol Crystallogr. 2005 Sep;61(Pt 9):1245-54. Epub 2005, Aug 16. PMID:16131758 doi:10.1107/S0907444905020251
3. ↑ Madrid DC, Ting LM, Waller KL, Schramm VL, Kim K. Plasmodium falciparum purine nucleoside phosphorylase is critical for viability of malaria parasites. J Biol Chem. 2008 Dec 19;283(51):35899-907. doi: 10.1074/jbc.M807218200. Epub, 2008 Oct 28. PMID:18957439 doi:http://dx.doi.org/10.1074/jbc.M807218200
4. ↑ Chaikuad A, Brady RL. Conservation of structure and activity in Plasmodium purine nucleoside phosphorylases. BMC Struct Biol. 2009 Jul 3;9:42. PMID:19575810 doi:10.1186/1472-6807-9-42
5. ↑ Donaldson TM, Ting LM, Zhan C, Shi W, Zheng R, Almo SC, Kim K. Structural determinants of the 5'-methylthioinosine specificity of Plasmodium purine nucleoside phosphorylase. PLoS One. 2014 Jan 8;9(1):e84384. doi: 10.1371/journal.pone.0084384. eCollection , 2014. PMID:24416224 doi:http://dx.doi.org/10.1371/journal.pone.0084384
6. ↑ Ducati RG, Namanja-Magliano HA, Harijan RK, Fajardo JE, Fiser A, Daily JP, Schramm VL. Genetic resistance to purine nucleoside phosphorylase inhibition in Plasmodium falciparum. Proc Natl Acad Sci U S A. 2018 Feb 12. pii: 1525670115. doi:, 10.1073/pnas.1525670115. PMID:29440412 doi:http://dx.doi.org/10.1073/pnas.1525670115