View source for 4nml


==2.60 Angstrom resolution crystal structure of putative ribose 5-phosphate isomerase from Toxoplasma gondii ME49 in complex with DL-Malic acid==
<StructureSection load='4nml' size='340' side='right'caption='[[4nml]], [[Resolution|resolution]] 2.60&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4nml]] is a 1 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=4NML OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4NML 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]] 2.6&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=CME:S,S-(2-HYDROXYETHYL)THIOCYSTEINE'>CME</scene>, <scene name='pdbligand=MLT:D-MALATE'>MLT</scene>, <scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</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=4nml FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4nml OCA], [https://pdbe.org/4nml PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4nml RCSB], [https://www.ebi.ac.uk/pdbsum/4nml PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4nml ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/S8GQK2_TOXGM S8GQK2_TOXGM] 
<div style="background-color:#fffaf0;">
== 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>
</div>
<div class="pdbe-citations 4nml" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Toxoplasma gondii ME49]]
[[Category: Anderson WF]]
[[Category: Dubrovska I]]
[[Category: Flores K]]
[[Category: Halavaty AS]]
[[Category: Ngo H]]
[[Category: Roos D]]
[[Category: Ruan J]]
[[Category: Shanmugam D]]
[[Category: Shuvalova L]]