View source for 5bxi


==1.7 Angstrom Resolution Crystal Structure of Putative Nucleoside Diphosphate Kinase from Toxoplasma gondii with Tyrosine of Tag Bound to Active Site==
<StructureSection load='5bxi' size='340' side='right'caption='[[5bxi]], [[Resolution|resolution]] 1.70&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5bxi]] is a 12 chain structure with sequence from [https://en.wikipedia.org/wiki/Toxoplasma_gondii_ME49 Toxoplasma gondii ME49]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5BXI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5BXI 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]] 1.7&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BCT:BICARBONATE+ION'>BCT</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</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=5bxi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5bxi OCA], [https://pdbe.org/5bxi PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5bxi RCSB], [https://www.ebi.ac.uk/pdbsum/5bxi PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5bxi ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/B9Q287_TOXGV B9Q287_TOXGV] 
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== Publication Abstract from PubMed ==
Toxoplasma gondii, an Apicomplexan parasite, causes significant morbidity and mortality, including severe disease in immunocompromised hosts and devastating congenital disease, with no effective treatment for the bradyzoite stage. To address this, we used the Tropical Disease Research database, crystallography, molecular modeling, and antisense to identify and characterize a range of potential therapeutic targets for toxoplasmosis. Phosphoglycerate mutase II (PGMII), nucleoside diphosphate kinase (NDK), ribulose phosphate 3-epimerase (RPE), ribose-5-phosphate isomerase (RPI), and ornithine aminotransferase (OAT) were structurally characterized. Crystallography revealed insights into the overall structure, protein oligomeric states and molecular details of active sites important for ligand recognition. Literature and molecular modeling suggested potential inhibitors and druggability. The targets were further studied with vivoPMO to interrupt enzyme synthesis, identifying the targets as potentially important to parasitic replication and, therefore, of therapeutic interest. Targeted vivoPMO resulted in statistically significant perturbation of parasite replication without concomitant host cell toxicity, consistent with a previous CRISPR/Cas9 screen showing PGM, RPE, and RPI contribute to parasite fitness. PGM, RPE, and RPI have the greatest promise for affecting replication in tachyzoites. These targets are shared between other medically important parasites and may have wider therapeutic potential.

CSGID Solves Structures and Identifies Phenotypes for Five Enzymes in Toxoplasma gondii.,Lykins JD, Filippova EV, Halavaty AS, Minasov G, Zhou Y, Dubrovska I, Flores KJ, Shuvalova LA, Ruan J, El Bissati K, Dovgin S, Roberts CW, Woods S, Moulton JD, Moulton H, McPhillie MJ, Muench SP, Fishwick CWG, Sabini E, Shanmugam D, Roos DS, McLeod R, Anderson WF, Ngo HM Front Cell Infect Microbiol. 2018 Oct 5;8:352. doi: 10.3389/fcimb.2018.00352. , eCollection 2018. PMID:30345257<ref>PMID:30345257</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Toxoplasma gondii ME49]]
[[Category: Anderson WF]]
[[Category: Dubrovska I]]
[[Category: Flores K]]
[[Category: Minasov G]]
[[Category: Ngo H]]
[[Category: Ruan J]]
[[Category: Shuvalova L]]