5nsd

Co-crystal structure of NAMPT dimer with KPT-9274

spinqualitylabelsall models 5nsd, resolution 2.05Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5nsd is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.046Å Ligands: 96Q, GOL, PO4 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function NAMPT_HUMAN Catalyzes the condensation of nicotinamide with 5-phosphoribosyl-1-pyrophosphate to yield nicotinamide mononucleotide, an intermediate in the biosynthesis of NAD. It is the rate limiting component in the mammalian NAD biosynthesis pathway (By similarity). Publication Abstract from PubMed Unraveling the mechanism of action and molecular target of small molecules remains a major challenge in drug discovery. While many cancer drugs target genetic vulnerabilities, loss-of-function screens fail to identify essential genes in drug mechanism of action. Here, we report CRISPRres, a CRISPR-Cas-based genetic screening approach to rapidly derive and identify drug resistance mutations in essential genes. It exploits the local genetic variation created by CRISPR-Cas-induced non-homologous end-joining (NHEJ) repair to generate a wide variety of functional in-frame mutations. Using large sgRNA tiling libraries and known drug-target pairs, we validate it as a target identification approach. We apply CRISPRres to the anticancer agent KPT-9274 and identify nicotinamide phosphoribosyltransferase (NAMPT) as its main target. These results present a powerful and simple genetic approach to create many protein variants that, in combination with positive selection, can be applied to reveal the cellular target of small-molecule inhibitors. Target identification of small molecules using large-scale CRISPR-Cas mutagenesis scanning of essential genes.,Neggers JE, Kwanten B, Dierckx T, Noguchi H, Voet A, Bral L, Minner K, Massant B, Kint N, Delforge M, Vercruysse T, Baloglu E, Senapedis W, Jacquemyn M, Daelemans D Nat Commun. 2018 Feb 5;9(1):502. doi: 10.1038/s41467-017-02349-8. PMID:29402884 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Phosphoribosyltransferase 3D structures

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