6u69: Difference between revisions

From Proteopedia
Jump to navigationJump to search
← Older edit
OCA (talk | contribs)
Bots, Bureaucrats, journal, Administrators
3,331,615 edits
No edit summary
OCA (talk | contribs)
Bots, Bureaucrats, journal, Administrators
3,331,615 edits
No edit summary
 
(2 intermediate revisions by the same user not shown)
Line 3: Line 3:
<StructureSection load='6u69' size='340' side='right'caption='[[6u69]], [[Resolution|resolution]] 2.61&Aring;' scene=''>
<StructureSection load='6u69' size='340' side='right'caption='[[6u69]], [[Resolution|resolution]] 2.61&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[6u69]] is a 1 chain structure. 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://oca.weizmann.ac.il/oca-docs/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"><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]] 2.61&#8491;</td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/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='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'>[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;">
== 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&reg;/PubMed&reg;, 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>
[[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]]
Retrieved from "https://proteopedia.org/6u69"