4tzr
From Proteopedia
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| - | ''' | + | ==Calcium-Dependent Protein Kinase 1 from Toxoplasma gondii (TgCDPK1) in complex with inhibitor UW1561== |
| + | <StructureSection load='4tzr' size='340' side='right' caption='[[4tzr]], [[Resolution|resolution]] 2.00Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[4tzr]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4TZR OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4TZR FirstGlance]. <br> | ||
| + | </td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=UW2:1-{4-AMINO-3-[2-(CYCLOPROPYLOXY)QUINOLIN-6-YL]-1H-PYRAZOLO[3,4-D]PYRIMIDIN-1-YL}-2-METHYLPROPAN-2-OL'>UW2</scene><br> | ||
| + | <tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4tzr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4tzr OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4tzr RCSB], [http://www.ebi.ac.uk/pdbsum/4tzr PDBsum]</span></td></tr> | ||
| + | <table> | ||
| + | <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®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | + | </div> | |
| - | + | == References == | |
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Merritt, E A.]] | ||
| + | [[Category: Atp-binding]] | ||
| + | [[Category: Bumped kinase inhibitor]] | ||
| + | [[Category: Calcium-binding]] | ||
| + | [[Category: Serine/threonine protein kinase]] | ||
| + | [[Category: Transferase]] | ||
Revision as of 08:38, 27 August 2014
Calcium-Dependent Protein Kinase 1 from Toxoplasma gondii (TgCDPK1) in complex with inhibitor UW1561
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