3fow: Difference between revisions
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==Plasmodium Purine Nucleoside Phosphorylase V66I-V73I-Y160F Mutant== | ==Plasmodium Purine Nucleoside Phosphorylase V66I-V73I-Y160F Mutant== | ||
<StructureSection load='3fow' size='340' side='right' caption='[[3fow]], [[Resolution|resolution]] 2.80Å' scene=''> | <StructureSection load='3fow' size='340' side='right' caption='[[3fow]], [[Resolution|resolution]] 2.80Å' scene=''> | ||
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<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PFE0660c, PNP ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=36329 PLAF7])</td></tr> | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PFE0660c, PNP ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=36329 PLAF7])</td></tr> | ||
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Uridine_phosphorylase Uridine phosphorylase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.4.2.3 2.4.2.3] </span></td></tr> | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Uridine_phosphorylase Uridine phosphorylase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.4.2.3 2.4.2.3] </span></td></tr> | ||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3fow FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3fow OCA], [http://pdbe.org/3fow PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3fow RCSB], [http://www.ebi.ac.uk/pdbsum/3fow PDBsum]</span></td></tr> | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3fow FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3fow OCA], [http://pdbe.org/3fow PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3fow RCSB], [http://www.ebi.ac.uk/pdbsum/3fow PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3fow ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Evolutionary Conservation == | == Evolutionary Conservation == | ||
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Check<jmol> | Check<jmol> | ||
<jmolCheckbox> | <jmolCheckbox> | ||
<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/fo/3fow_consurf.spt"</scriptWhenChecked> | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/fo/3fow_consurf.spt"</scriptWhenChecked> | ||
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | ||
<text>to colour the structure by Evolutionary Conservation</text> | <text>to colour the structure by Evolutionary Conservation</text> | ||
Revision as of 10:48, 5 December 2018
Plasmodium Purine Nucleoside Phosphorylase V66I-V73I-Y160F MutantPlasmodium Purine Nucleoside Phosphorylase V66I-V73I-Y160F Mutant
Structural highlights
Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedPlasmodium parasites rely upon purine salvage for survival. Plasmodium purine nucleoside phosphorylase is part of the streamlined Plasmodium purine salvage pathway that leads to the phosphorylysis of both purines and 5'-methylthiopurines, byproducts of polyamine synthesis. We have explored structural features in Plasmodium falciparum purine nucleoside phosphorylase (PfPNP) that affect efficiency of catalysis as well as those that make it suitable for dual specificity. We used site directed mutagenesis to identify residues critical for PfPNP catalytic activity as well as critical residues within a hydrophobic pocket required for accommodation of the 5'-methylthio group. Kinetic analysis data shows that several mutants had disrupted binding of the 5'-methylthio group while retaining activity for inosine. A triple PfPNP mutant that mimics Toxoplasma gondii PNP had significant loss of 5'-methylthio activity with retention of inosine activity. Crystallographic investigation of the triple mutant PfPNP with Tyr160Phe, Val66Ile, andVal73Ile in complex with the transition state inhibitor immucillin H reveals fewer hydrogen bond interactions for the inhibitor in the hydrophobic pocket. Structural determinants of the 5'-methylthioinosine specificity of Plasmodium purine nucleoside phosphorylase.,Donaldson TM, Ting LM, Zhan C, Shi W, Zheng R, Almo SC, Kim K PLoS One. 2014 Jan 8;9(1):e84384. doi: 10.1371/journal.pone.0084384. eCollection , 2014. PMID:24416224[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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