2bsx: Difference between revisions
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==Overview== | ==Overview== | ||
Purine metabolism in the parasite Plasmodium has been identified as a, promising target for antimalarial therapies. Purine nucleoside, phosphorylase (PNP) is part of a salvage pathway for the biosynthesis of, purines, which are essential for parasite survival. Two crystal structures, of PNP from Plasmodium falciparum (PfPNP) in two space groups, each with a, single subunit in the asymmetric unit, are described here. One structure, refined to 2.4 A, has an empty nucleoside-binding site and a sulfate ion, bound in the phosphate-binding pocket. The second structure, refined to, 2.0 A, has the substrate inosine bound to the active centre. Structure, comparison reveals alterations in the active site upon ligand binding. The, new structures presented here specifically highlight the likely roles ... | Purine metabolism in the parasite Plasmodium has been identified as a, promising target for antimalarial therapies. Purine nucleoside, phosphorylase (PNP) is part of a salvage pathway for the biosynthesis of, purines, which are essential for parasite survival. Two crystal structures, of PNP from Plasmodium falciparum (PfPNP) in two space groups, each with a, single subunit in the asymmetric unit, are described here. One structure, refined to 2.4 A, has an empty nucleoside-binding site and a sulfate ion, bound in the phosphate-binding pocket. The second structure, refined to, 2.0 A, has the substrate inosine bound to the active centre. Structure, comparison reveals alterations in the active site upon ligand binding. The, new structures presented here specifically highlight the likely roles of, Asp206 and two loops flanking the active site: the beta7-alpha6 loop, (residues approximately 161-169) and the beta9-alpha8 loop (residues, approximately 208-223). Comparison with PNP in complex with, transition-state inhibitors suggests that the purine substrate moves, towards the phosphate substrate, rather than vice versa, upon forming the, transition state. The single-substrate-containing PfPNP structures also, appear to be more flexible than PfPNP bound to inhibitors. Together, these, structures serve as a basis for better understanding of ligand binding and, mechanism that can be further exploited to optimize the specificity of, anti-PfPNP drugs. | ||
==About this Structure== | ==About this Structure== | ||
2BSX is a | 2BSX is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Plasmodium_falciparum Plasmodium falciparum] with NOS as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Purine-nucleoside_phosphorylase Purine-nucleoside phosphorylase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.4.2.1 2.4.2.1] Structure known Active Site: AC1. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=2BSX OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: uridine phosphorylase]] | [[Category: uridine phosphorylase]] | ||
''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on | ''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 5 14:09:09 2007'' | ||
Revision as of 15:03, 5 November 2007
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CRYSTAL STRUCTURE OF THE PLASMODIUM FALCIPARUM PURINE NUCLEOSIDE PHOSPHORYLASE COMPLEXED WITH INOSINE
OverviewOverview
Purine metabolism in the parasite Plasmodium has been identified as a, promising target for antimalarial therapies. Purine nucleoside, phosphorylase (PNP) is part of a salvage pathway for the biosynthesis of, purines, which are essential for parasite survival. Two crystal structures, of PNP from Plasmodium falciparum (PfPNP) in two space groups, each with a, single subunit in the asymmetric unit, are described here. One structure, refined to 2.4 A, has an empty nucleoside-binding site and a sulfate ion, bound in the phosphate-binding pocket. The second structure, refined to, 2.0 A, has the substrate inosine bound to the active centre. Structure, comparison reveals alterations in the active site upon ligand binding. The, new structures presented here specifically highlight the likely roles of, Asp206 and two loops flanking the active site: the beta7-alpha6 loop, (residues approximately 161-169) and the beta9-alpha8 loop (residues, approximately 208-223). Comparison with PNP in complex with, transition-state inhibitors suggests that the purine substrate moves, towards the phosphate substrate, rather than vice versa, upon forming the, transition state. The single-substrate-containing PfPNP structures also, appear to be more flexible than PfPNP bound to inhibitors. Together, these, structures serve as a basis for better understanding of ligand binding and, mechanism that can be further exploited to optimize the specificity of, anti-PfPNP drugs.
About this StructureAbout this Structure
2BSX is a Single protein structure of sequence from Plasmodium falciparum with NOS as ligand. Active as Purine-nucleoside phosphorylase, with EC number 2.4.2.1 Structure known Active Site: AC1. Full crystallographic information is available from OCA.
ReferenceReference
Structures of Plasmodium falciparum purine nucleoside phosphorylase complexed with sulfate and its natural substrate inosine., Schnick C, Robien MA, Brzozowski AM, Dodson EJ, Murshudov GN, Anderson L, Luft JR, Mehlin C, Hol WG, Brannigan JA, Wilkinson AJ, Acta Crystallogr D Biol Crystallogr. 2005 Sep;61(Pt 9):1245-54. Epub 2005, Aug 16. PMID:16131758
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