7ore

Crystal structure of JNK3 in complex with light-activated covalent inhibitor MR-II-249 with both non-covalent and covalent binding modes (compound 4)

spinqualitylabelsall models 7ore, resolution 2.18Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.18Å Ligands: 0EI, EDO Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed Covalent kinase inhibitors account for some of the most successful drugs that have recently entered the clinic and many others are in preclinical development. A common strategy is to target cysteines in the vicinity of the ATP binding site using an acrylamide electrophile. To increase the tissue selectivity of kinase inhibitors, it could be advantageous to control the reactivity of these electrophiles with light. Here, we introduce covalent inhibitors of the kinase JNK3 that function as photoswitchable affinity labels (PALs). Our lead compounds contain a diazocine photoswitch, are poor non-covalent inhibitors in the dark, and becomes effective covalent inhibitors after irradiation with visible light. Our proposed mode of action is supported by X-ray structures that explain why these compounds are unreactive in the dark and undergo proximity-based covalent attachment following exposure to light. Controlling the Covalent Reactivity of a Kinase Inhibitor with Light.,Reynders M, Chaikuad A, Berger BT, Bauer K, Koch P, Laufer S, Knapp S, Trauner D Angew Chem Int Ed Engl. 2021 Jun 3. doi: 10.1002/anie.202103767. PMID:34081840 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Mitogen-activated protein kinase 3D structures

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