3mb8: Difference between revisions
No edit summary |
No edit summary |
||
| (11 intermediate revisions by the same user not shown) | |||
| Line 1: | Line 1: | ||
The | ==Crystal structure of purine nucleoside phosphorylase from toxoplasma gondii in complex with immucillin-H== | ||
<StructureSection load='3mb8' size='340' side='right'caption='[[3mb8]], [[Resolution|resolution]] 1.90Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[3mb8]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Toxoplasma_gondii Toxoplasma gondii]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3MB8 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3MB8 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]] 1.9Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=IMH:1,4-DIDEOXY-4-AZA-1-(S)-(9-DEAZAHYPOXANTHIN-9-YL)-D-RIBITOL'>IMH</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</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=3mb8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3mb8 OCA], [https://pdbe.org/3mb8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3mb8 RCSB], [https://www.ebi.ac.uk/pdbsum/3mb8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3mb8 ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/Q2HXR2_TOXGO Q2HXR2_TOXGO] | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
The intracellular pathogen Toxoplasma gondii is a purine auxotroph that relies on purine salvage for proliferation. We have optimized T. gondii purine nucleoside phosphorylase (TgPNP) stability and crystallized TgPNP with phosphate and Immucillin-H, a transition-state analogue that has high affinity for the enzyme. Immucillin-H bound to TgPNP with a dissociation constant of 370 pM, the highest affinity of eleven immucillins selected to probe the catalytic site. The specificity for transition-state analogues indicated an early dissociative transition state for TgPNP. Compared with PfPNP, large substituents surrounding the 5' -hydroxyl group of inhibitors demonstrate reduced capacity for TgPNP inhibition. Catalytic discrimination against large 5' groups is consistent with the inability of TgPNP to catalyze the phosphorylysis of 5' -methylthioinosine to hypoxanthine. In contrast to mammalian PNP, the 2' -hydroxyl group is crucial for inhibitor binding in the catalytic site of TgPNP. This first crystal structure of TgPNP describes the basis for discrimination against 5' -methylthioinosine and similarly 5' -hydroxy-substituted immucillins; structural differences reflect the unique adaptations of purine salvage pathways of Apicomplexa. | |||
INHIBITION AND STRUCTURE OF TOXOPLASMA GONDII PURINE NUCLEOSIDE PHOSPHORYLASE.,Donaldson TM, Cassera MB, Ho MC, Zhan C, Merino EF, Evans GB, Tyler PC, Almo SC, Schramm VL, Kim K Eukaryot Cell. 2014 Feb 28. PMID:24585883<ref>PMID:24585883</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 3mb8" 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: Toxoplasma gondii]] | |||
[[Category: Almo SC]] | |||
[[Category: Ho M]] | |||
[[Category: Schramm VL]] | |||