6ko6

Crystal structure of AMPPNP bound Cka1 from C. neoformans

spinqualitylabelsall models 6ko6, resolution 2.40Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6ko6 is a 1 chain structure with sequence from Cryptococcus neoformans var. grubii H99. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.4Å Ligands: ANP, MG, SO4 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function J9VNH4_CRYNH Publication Abstract from PubMed CK2alpha is a constitutively active and highly conserved serine/threonine protein kinase that is involved in the regulation of key cellular metabolic pathways and associated with a variety of tumours and cancers. The most well-known CK2alpha inhibitor is the human clinical trial candidate CX-4945, which has recently shown to exhibit not only anti-cancer, but also anti-fungal properties. This prompted us to work on the CK2alpha orthologue, Cka1, from the pathogenic fungus Cryptococcus neoformans, which causes life-threatening systemic cryptococcosis and meningoencephalitis mainly in immunocompromised individuals. At present, treatment of cryptococcosis remains a challenge due to limited anti-cryptococcal therapeutic strategies. Hence, expanding therapeutic options for the treatment of the disease is highly clinically relevant. Herein, we report the structures of Cka1-AMPPNP-Mg(2+) (2.40 A) and Cka1-CX-4945 (2.09 A). Structural comparisons of Cka1-AMPPNP-Mg(2+) with other orthologues revealed the dynamic architecture of the N-lobe across species. This may explain for the difference in binding affinities and deviations in protein-inhibitor interactions between Cka1-CX-4945 and human CK2alpha-CX-4945. Supporting it, in vitro kinase assay demonstrated that CX-4945 inhibited human CK2alpha much more efficiently than Cka1. Our results provide structural insights into the design of more selective inhibitors against Cka1. Structural analysis of fungal pathogenicity-related casein kinase alpha subunit, Cka1, in the human fungal pathogen Cryptococcus neoformans.,Ong BX, Yoo Y, Han MG, Park JB, Choi MK, Choi Y, Shin JS, Bahn YS, Cho HS Sci Rep. 2019 Oct 7;9(1):14398. doi: 10.1038/s41598-019-50678-z. PMID:31591414 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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