View source for 3enz


==Arsenolytic structure of Plasmodium falciparum purine nucleoside phosphorylase with hypoxanthine, ribose and arsenate ion==
<StructureSection load='3enz' size='340' side='right'caption='[[3enz]], [[Resolution|resolution]] 2.03&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[3enz]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Plasmodium_falciparum_3D7 Plasmodium falciparum 3D7]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3ENZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3ENZ FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.03&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ART:ARSENATE'>ART</scene>, <scene name='pdbligand=FMT:FORMIC+ACID'>FMT</scene>, <scene name='pdbligand=HPA:HYPOXANTHINE'>HPA</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=R1X:1,4-ANHYDRO-D-RIBITOL'>R1X</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3enz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3enz OCA], [https://pdbe.org/3enz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3enz RCSB], [https://www.ebi.ac.uk/pdbsum/3enz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3enz ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/PNPH_PLAF7 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]<ref>PMID:14982926</ref> <ref>PMID:16131758</ref> <ref>PMID:18957439</ref> <ref>PMID:19575810</ref> <ref>PMID:24416224</ref> <ref>PMID:29440412</ref> 
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/en/3enz_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=3enz ConSurf].
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== Publication Abstract from PubMed ==
BACKGROUND: Purine nucleoside phosphorylase (PNP) is central to purine salvage mechanisms in Plasmodium parasites, the causative agents of malaria. Most human malaria results from infection either by Plasmodium falciparum (Pf), the deadliest form of the parasite, or by the widespread Plasmodium vivax (Pv). Whereas the PNP enzyme from Pf has previously been studied in detail, despite the prevalence of Pv little is known about many of the key metabolic enzymes from this parasite, including PvPNP. RESULTS: The crystal structure of PvPNP is described and is seen to have many features in common with the previously reported structure of PfPNP. In particular, the composition and conformations of the active site regions are virtually identical. The crystal structure of a complex of PfPNP co-crystallised with inosine and arsenate is also described, and is found to contain a mixture of products and reactants - hypoxanthine, ribose and arsenate. The ribose C1' in this hybrid complex lies close to the expected point of symmetry along the PNP reaction coordinate, consistent with a conformation between the transition and product states. These two Plasmodium PNP structures confirm the similarity of structure and mechanism of these enzymes, which are also confirmed in enzyme kinetic assays using an array of substrates. These reveal an unusual form of substrate activation by 2'-deoxyinosine of PvPNP, but not PfPNP. CONCLUSION: The close similarity of the Pf and Pv PNP structures allows characteristic features to be identified that differentiate the Apicomplexa PNPs from the human host enzyme. This similarity also suggests there should be a high level of cross-reactivity for compounds designed to inhibit either of these molecular targets. However, despite these similarities, there are also small differences in the activities of the two Plasmodium enzymes.

Conservation of structure and activity in Plasmodium purine nucleoside phosphorylases.,Chaikuad A, Brady RL BMC Struct Biol. 2009 Jul 3;9:42. PMID:19575810<ref>PMID:19575810</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 3enz" style="background-color:#fffaf0;"></div>

==See Also==
*[[Purine nucleoside phosphorylase 3D structures|Purine nucleoside phosphorylase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Plasmodium falciparum 3D7]]
[[Category: Brady RL]]
[[Category: Chaikuad A]]