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| | <StructureSection load='3i7c' size='340' side='right'caption='[[3i7c]], [[Resolution|resolution]] 1.98Å' scene=''> | | <StructureSection load='3i7c' size='340' side='right'caption='[[3i7c]], [[Resolution|resolution]] 1.98Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3i7c]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Toxgo Toxgo]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3I7C OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3I7C FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3i7c]] 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=3I7C OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3I7C FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BK2:1-TERT-BUTYL-3-NAPHTHALEN-2-YL-1H-PYRAZOLO[3,4-D]PYRIMIDIN-4-AMINE'>BK2</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.98Å</td></tr> |
| - | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BK2:1-TERT-BUTYL-3-NAPHTHALEN-2-YL-1H-PYRAZOLO[3,4-D]PYRIMIDIN-4-AMINE'>BK2</scene>, <scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[3i79|3i79]], [[3i7b|3i7b]], [[3n51|3n51]], [[3mwu|3mwu]], [[3ncg|3ncg]]</div></td></tr>
| + | |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CDPK1, TgCDPK1 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=5811 TOXGO])</td></tr>
| + | |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Calcium/calmodulin-dependent_protein_kinase Calcium/calmodulin-dependent protein kinase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.17 2.7.11.17] </span></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=3i7c FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3i7c OCA], [https://pdbe.org/3i7c PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3i7c RCSB], [https://www.ebi.ac.uk/pdbsum/3i7c PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3i7c ProSAT]</span></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=3i7c FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3i7c OCA], [https://pdbe.org/3i7c PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3i7c RCSB], [https://www.ebi.ac.uk/pdbsum/3i7c PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3i7c ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/Q9BJF5_TOXGO Q9BJF5_TOXGO] |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Calcium/calmodulin-dependent protein kinase]] | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Toxgo]] | + | [[Category: Toxoplasma gondii]] |
| - | [[Category: Larson, E T]] | + | [[Category: Larson ET]] |
| - | [[Category: Structural genomic]]
| + | [[Category: Merritt EA]] |
| - | [[Category: Merritt, E A]] | + | |
| - | [[Category: Atp-binding]]
| + | |
| - | [[Category: Bumped kinase inhibitor]]
| + | |
| - | [[Category: Calmodulin]]
| + | |
| - | [[Category: Ef hand]]
| + | |
| - | [[Category: Kinase]]
| + | |
| - | [[Category: Msgpp]]
| + | |
| - | [[Category: Nucleotide-binding]]
| + | |
| - | [[Category: Protein kinase]]
| + | |
| - | [[Category: Serine/threonine-protein kinase]]
| + | |
| - | [[Category: Transferase]]
| + | |
| Structural highlights
Function
Q9BJF5_TOXGO
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
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[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ 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. Toxoplasma gondii calcium-dependent protein kinase 1 is a target for selective kinase inhibitors. Nat Struct Mol Biol. 2010 May;17(5):602-7. Epub 2010 May 2. PMID:20436472 doi:10.1038/nsmb.1818
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