View source for 3i7b


==Calcium-Dependent Protein Kinase 1 from Toxoplasma gondii (TgCDPK1) in complex with bumped kinase inhibitor NM-PP1==
<StructureSection load='3i7b' size='340' side='right'caption='[[3i7b]], [[Resolution|resolution]] 1.99&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[3i7b]] 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=3I7B OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3I7B 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]] 1.988&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BK1:1-(1-METHYLETHYL)-3-(NAPHTHALEN-1-YLMETHYL)-1H-PYRAZOLO[3,4-D]PYRIMIDIN-4-AMINE'>BK1</scene>, <scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</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=3i7b FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3i7b OCA], [https://pdbe.org/3i7b PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3i7b RCSB], [https://www.ebi.ac.uk/pdbsum/3i7b PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3i7b ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/Q9BJF5_TOXGO Q9BJF5_TOXGO] 
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/i7/3i7b_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=3i7b ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
New drugs are needed to treat toxoplasmosis. Toxoplasma gondii calcium-dependent protein kinases (TgCDPKs) are attractive targets because they are absent in mammals. We show that TgCDPK1 is inhibited by low nanomolar levels of bumped kinase inhibitors (BKIs), compounds inactive against mammalian kinases. Cocrystal structures of TgCDPK1 with BKIs confirm that the structural basis for selectivity is due to the unique glycine gatekeeper residue in the ATP-binding site. We show that BKIs interfere with an early step in T. gondii infection of human cells in culture. Furthermore, we show that TgCDPK1 is the in vivo target of BKIs because T. gondii expressing a glycine to methionine gatekeeper mutant enzyme show significantly decreased sensitivity to BKIs. Thus, design of selective TgCDPK1 inhibitors with low host toxicity may be achievable.

Toxoplasma gondii calcium-dependent protein kinase 1 is a target for selective kinase inhibitors.,Ojo KK, Larson ET, Keyloun KR, Castaneda LJ, Derocher AE, Inampudi KK, Kim JE, Arakaki TL, Murphy RC, Zhang L, Napuli AJ, Maly DJ, Verlinde CL, Buckner FS, Parsons M, Hol WG, Merritt EA, Van Voorhis WC Nat Struct Mol Biol. 2010 May;17(5):602-7. Epub 2010 May 2. PMID:20436472<ref>PMID:20436472</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 3i7b" style="background-color:#fffaf0;"></div>

==See Also==
*[[Calcium-dependent protein kinase|Calcium-dependent protein kinase]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Toxoplasma gondii]]
[[Category: Larson ET]]
[[Category: Merritt EA]]