1td1: Difference between revisions
No edit summary |
No edit summary |
||
| Line 1: | Line 1: | ||
[[Image:1td1.gif|left|200px]] | [[Image:1td1.gif|left|200px]] | ||
<!-- | |||
The line below this paragraph, containing "STRUCTURE_1td1", creates the "Structure Box" on the page. | |||
You may change the PDB parameter (which sets the PDB file loaded into the applet) | |||
or the SCENE parameter (which sets the initial scene displayed when the page is loaded), | |||
or leave the SCENE parameter empty for the default display. | |||
--> | |||
{{STRUCTURE_1td1| PDB=1td1 | SCENE= }} | |||
}} | |||
'''Crystal Structure of the Purine Nucleoside Phosphorylase from Schistosoma mansoni in complex with acetate''' | '''Crystal Structure of the Purine Nucleoside Phosphorylase from Schistosoma mansoni in complex with acetate''' | ||
| Line 30: | Line 27: | ||
[[Category: Garratt, R C.]] | [[Category: Garratt, R C.]] | ||
[[Category: Pereira, H D.]] | [[Category: Pereira, H D.]] | ||
[[Category: | [[Category: Purine nucleoside phosphorylase]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 09:48:31 2008'' | |||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | |||
Revision as of 09:48, 3 May 2008
Crystal Structure of the Purine Nucleoside Phosphorylase from Schistosoma mansoni in complex with acetate
OverviewOverview
Despite the availability of effective chemotherapy, schistosomiasis continues to be one of the major parasitic infections to affect the human population worldwide. Currently, little is known of the structural biology of the parasites that are responsible for the disease and few attempts have been made to develop second generation drugs, which may become essential if resistance to those currently available becomes an issue. Here, we describe three crystal structures for the enzyme purine nucleoside phosphorylase (PNP) from Schistosoma mansoni, a component of the purine salvage pathway. PNP is known to be essential for the recovery of purine bases and nucleosides in schistosomes, due to an absence of the enzymes for de novo synthesis, making it a sensitive point in the parasite's metabolism. In all three structures reported here, acetate occupies part of the base-binding site and is directly bound to the conserved glutamic acid at position 203. One of the structures presents the crystallization additive sulfobetaine 195 (NDSB195) occupying simultaneously the ribose and phosphate binding sites, whilst a second presents only phosphate in the latter. The observation of sulfobetaine specifically bound to the protein active site was unexpected and is unique to this structure as far as we are aware. Considerable flexibility is observed in the active site, principally due to variable structural disorder in the regions centered on residues 64 and 260. This conformational plasticity extends to the way in which both NDSB195 and phosphate bind to the individual monomers of the trimeric structure reported here. Differences between the parasite and human enzymes are limited principally to the base-binding site, where the substitution of V245 in the mammalian enzymes by S247 introduces additional hydrogen bonding potential to the site. This is satisfied in the structures described here by a water molecule whose presence is normally observed only in complexes with 6-oxopurines. Residue Y202, which replaces F200 in human PNP, is able to reach over the ribose-binding site to interact with H259 and is predicted to form an additional hydrogen bond with the 5' hydroxyl of nucleoside substrates.
About this StructureAbout this Structure
1TD1 is a Single protein structure of sequence from Schistosoma mansoni. Full crystallographic information is available from OCA.
ReferenceReference
Structures for the potential drug target purine nucleoside phosphorylase from Schistosoma mansoni causal agent of schistosomiasis., Pereira HD, Franco GR, Cleasby A, Garratt RC, J Mol Biol. 2005 Oct 28;353(3):584-99. Epub 2005 Sep 2. PMID:16182308 Page seeded by OCA on Sat May 3 09:48:31 2008