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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://proteopedia.org/fgij/fg.htm?mol=6U69 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6u69]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Candida_albicans_SC5314 Candida albicans SC5314]. 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 [https://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" 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> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.61Å</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='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='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> | + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6u69 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6u69 OCA], [https://pdbe.org/6u69 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6u69 RCSB], [https://www.ebi.ac.uk/pdbsum/6u69 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6u69 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/A0A1D8PKB4_CANAL A0A1D8PKB4_CANAL] |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Canal]] | + | [[Category: Candida albicans SC5314]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Structural genomic]] | + | [[Category: Di Leo R]] |
| - | [[Category: Evdokimova, E]] | + | [[Category: Evdokimova E]] |
| - | [[Category: Joachimiak, A]] | + | [[Category: Joachimiak A]] |
| - | [[Category: Leo, R Di]]
| + | [[Category: Satchell KJF]] |
| - | [[Category: Satchell, K J.F]] | + | [[Category: Savchenko A]] |
| - | [[Category: Savchenko, A]] | + | [[Category: Stogios PJ]] |
| - | [[Category: Stogios, P J]] | + | |
| - | [[Category: Casein kinase 1]]
| + | |
| - | [[Category: Csgid]]
| + | |
| - | [[Category: Kinase]]
| + | |
| - | [[Category: National institute of allergy and infectious disease]]
| + | |
| - | [[Category: Niaid]]
| + | |
| - | [[Category: Transferase]]
| + | |
| - | [[Category: Yck2]]
| + | |
| Structural highlights
Function
A0A1D8PKB4_CANAL
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[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ 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. Overcoming Fungal Echinocandin Resistance through Inhibition of the Non-essential Stress Kinase Yck2. 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 doi:http://dx.doi.org/10.1016/j.chembiol.2019.12.008
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