View source for 4yjn


==Calcium-Dependent Protein Kinase 1 from Toxoplasma gondii (TgCDPK1) in complex with inhibitor UW1639==
<StructureSection load='4yjn' size='340' side='right'caption='[[4yjn]], [[Resolution|resolution]] 2.60&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4yjn]] is a 1 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=4YJN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4YJN 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=UW4:5-AMINO-1-TERT-BUTYL-3-[2-(CYCLOBUTYLOXY)QUINOLIN-6-YL]-1H-PYRAZOLE-4-CARBOXAMIDE'>UW4</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=4yjn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4yjn OCA], [https://pdbe.org/4yjn PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4yjn RCSB], [https://www.ebi.ac.uk/pdbsum/4yjn PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4yjn ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/Q9BJF5_TOXGO Q9BJF5_TOXGO] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
We previously discovered compounds based on a 5-aminopyrazole-4-carboxamide scaffold to be potent and selective inhibitors of CDPK1 from T. gondii. The current work, through structure-activity relationship studies, led to the discovery of compounds (34 and 35) with improved characteristics over the starting inhibitor 1 in terms of solubility, plasma exposure after oral administration in mice, or efficacy on parasite growth inhibition. Compounds 34 and 35 were further demonstrated to be more effective than 1 in a mouse infection model and markedly reduced the amount of T. gondii in the brain, spleen, and peritoneal fluid, and 35 given at 20 mg/kg eliminated T. gondii from the peritoneal fluid.

SAR Studies of 5-Aminopyrazole-4-carboxamide Analogues as Potent and Selective Inhibitors of CDPK1.,Huang W, Ojo KK, Zhang Z, Rivas K, Vidadala RS, Scheele S, DeRocher AE, Choi R, Hulverson MA, Barrett LK, Bruzual I, Siddaramaiah LK, Kerchner KM, Kurnick MD, Freiberg GM, Kempf D, Hol WG, Merritt EA, Neckermann G, de Hostos EL, Isoherranen N, Maly DJ, Parsons M, Doggett JS, Van Voorhis WC, Fan E ACS Med Chem Lett. 2015 Oct 22;6(12):1184-1189. eCollection 2015 Dec 10. PMID:26693272<ref>PMID:26693272</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4yjn" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Toxoplasma gondii]]
[[Category: Merritt EA]]