6u69

Crystal structure of Yck2 from Candida albicans, apoenzyme

spinqualitylabelsall models 6u69, resolution 2.61Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6u69 is a 1 chain structure with sequence from Candida albicans SC5314. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.61Å Ligands: CL, GOL, SO4 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT 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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Serine/threonine protein kinase 3D structures

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