6u69
From Proteopedia
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<StructureSection load='6u69' size='340' side='right'caption='[[6u69]], [[Resolution|resolution]] 2.61Å' scene=''> | <StructureSection load='6u69' size='340' side='right'caption='[[6u69]], [[Resolution|resolution]] 2.61Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>[[6u69]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Canal Canal]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6U69 OCA]. For a <b>guided tour on the structure components</b> use [http:// | + | <table><tr><td colspan='2'>[[6u69]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Canal Canal]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6U69 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6U69 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> | + | </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=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> |
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">YCK2, orf19.7001, CAALFM_C305650WA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=237561 CANAL])</td></tr> | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">YCK2, orf19.7001, CAALFM_C305650WA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=237561 CANAL])</td></tr> | ||
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http:// | + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6u69 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6u69 OCA], [http://pdbe.org/6u69 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6u69 RCSB], [http://www.ebi.ac.uk/pdbsum/6u69 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6u69 ProSAT]</span></td></tr> |
</table> | </table> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | New strategies are urgently needed to counter the threat to human health posed by drug-resistant fungi. To explore an as-yet unexploited target space for antifungals, we screened a library of protein kinase inhibitors for the ability to reverse resistance of the most common human fungal pathogen, Candida albicans, to caspofungin, a widely used antifungal. This screen identified multiple 2,3-aryl-pyrazolopyridine scaffold compounds capable of restoring caspofungin sensitivity. Using chemical genomic, biochemical, and structural approaches, we established the target for our most potent compound as Yck2, a casein kinase 1 family member. Combination of this compound with caspofungin eradicated drug-resistant C. albicans infection while sparing co-cultured human cells. In mice, genetic depletion of YCK2 caused an approximately 3-log10 decline in fungal burden in a model of systemic caspofungin-resistant C. albicans infection. Structural insights and our tool compound's profile in culture support targeting the Yck2 kinase function as a broadly active antifungal strategy. | ||
| + | |||
| + | Overcoming Fungal Echinocandin Resistance through Inhibition of the Non-essential Stress Kinase Yck2.,Caplan T, Lorente-Macias A, Stogios PJ, Evdokimova E, Hyde S, Wellington MA, Liston S, Iyer KR, Puumala E, Shekhar-Guturja T, Robbins N, Savchenko A, Krysan DJ, Whitesell L, Zuercher WJ, Cowen LE Cell Chem Biol. 2020 Mar 19;27(3):269-282.e5. doi:, 10.1016/j.chembiol.2019.12.008. Epub 2020 Jan 7. PMID:31924499<ref>PMID:31924499</ref> | ||
| + | |||
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 6u69" style="background-color:#fffaf0;"></div> | ||
| + | |||
| + | ==See Also== | ||
| + | *[[Serine/threonine protein kinase 3D structures|Serine/threonine protein kinase 3D structures]] | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
Revision as of 05:58, 13 May 2020
Crystal structure of Yck2 from Candida albicans, apoenzyme
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