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<StructureSection load='3ozf' size='340' side='right'caption='[[3ozf]], [[Resolution|resolution]] 1.94&Aring;' scene=''>
<StructureSection load='3ozf' size='340' side='right'caption='[[3ozf]], [[Resolution|resolution]] 1.94&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[3ozf]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Plafg Plafg]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3OZF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3OZF FirstGlance]. <br>
<table><tr><td colspan='2'>[[3ozf]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Plasmodium_falciparum_FCR-3/Gambia Plasmodium falciparum FCR-3/Gambia]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3OZF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3OZF FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=HPA:HYPOXANTHINE'>HPA</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene>, <scene name='pdbligand=POP:PYROPHOSPHATE+2-'>POP</scene></td></tr>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.944&#8491;</td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[3ozg|3ozg]]</div></td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=HPA:HYPOXANTHINE'>HPA</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene>, <scene name='pdbligand=POP:PYROPHOSPHATE+2-'>POP</scene></td></tr>
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">LACZ ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=5838 PLAFG])</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=3ozf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3ozf OCA], [https://pdbe.org/3ozf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3ozf RCSB], [https://www.ebi.ac.uk/pdbsum/3ozf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3ozf ProSAT]</span></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=3ozf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3ozf OCA], [https://pdbe.org/3ozf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3ozf RCSB], [https://www.ebi.ac.uk/pdbsum/3ozf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3ozf ProSAT]</span></td></tr>
</table>
</table>
== Function ==
== Function ==
[[https://www.uniprot.org/uniprot/HGXR_PLAFG HGXR_PLAFG]] Converts guanine to guanosine monophosphate, and hypoxanthine to inosine monophosphate. Transfers the 5-phosphoribosyl group from 5-phosphoribosylpyrophosphate onto the purine. Works with guanine, hypoxanthine and xanthine. Plays a central role in the generation of purine nucleotides through the purine salvage pathway.  
[https://www.uniprot.org/uniprot/HGXR_PLAFG HGXR_PLAFG] Converts guanine to guanosine monophosphate, and hypoxanthine to inosine monophosphate. Transfers the 5-phosphoribosyl group from 5-phosphoribosylpyrophosphate onto the purine. Works with guanine, hypoxanthine and xanthine. Plays a central role in the generation of purine nucleotides through the purine salvage pathway.
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Plasmodium falciparum, the primary cause of deaths from malaria, is a purine auxotroph and relies on hypoxanthine salvage from the host purine pool. Purine starvation as an antimalarial target has been validated by inhibition of purine nucleoside phosphorylase. Hypoxanthine depletion kills Plasmodium falciparum in cell culture and in Aotus monkey infections. Hypoxanthine-guanine-xanthine phosphoribosyltransferase (HGXPRT) from P. falciparum is required for hypoxanthine salvage by forming inosine 5'-monophosphate, a branchpoint for all purine nucleotide synthesis in the parasite. Here, we present a class of HGXPRT inhibitors, the acyclic immucillin phosphonates (AIPs), and cell permeable AIP prodrugs. The AIPs are simple, potent, selective, and biologically stable inhibitors. The AIP prodrugs block proliferation of cultured parasites by inhibiting the incorporation of hypoxanthine into the parasite nucleotide pool and validates HGXPRT as a target in malaria.
 
Acyclic Immucillin Phosphonates: Second-Generation Inhibitors of Plasmodium falciparum Hypoxanthine- Guanine-Xanthine Phosphoribosyltransferase.,Hazleton KZ, Ho MC, Cassera MB, Clinch K, Crump DR, Rosario I Jr, Merino EF, Almo SC, Tyler PC, Schramm VL Chem Biol. 2012 Jun 22;19(6):721-30. PMID:22726686<ref>PMID:22726686</ref>
 
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 3ozf" style="background-color:#fffaf0;"></div>


==See Also==
==See Also==
*[[Phosphoribosyltransferase 3D structures|Phosphoribosyltransferase 3D structures]]
*[[Phosphoribosyltransferase 3D structures|Phosphoribosyltransferase 3D structures]]
== References ==
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Large Structures]]
[[Category: Large Structures]]
[[Category: Plafg]]
[[Category: Plasmodium falciparum FCR-3/Gambia]]
[[Category: Almo, S C]]
[[Category: Almo SC]]
[[Category: Hazleton, K Z]]
[[Category: Hazleton KZ]]
[[Category: Ho, M]]
[[Category: Ho M]]
[[Category: Schramm, V L]]
[[Category: Schramm VL]]
[[Category: Hypoxanthine]]
[[Category: Transferase-transferase inhibitor complex]]

Latest revision as of 10:37, 21 February 2024

Crystal Structure of Plasmodium falciparum Hypoxanthine-Guanine-Xanthine Phosphoribosyltransferase in complex with hypoxanthine

3ozf, resolution 1.94Å

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