3wzu | pdb_00003wzu

THE STRUCTURE OF MAP2K7 IN COMPLEX WITH 5Z-7-oxozeaenol

spinqualitylabelsall models 3wzu, resolution 3.01Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 3wzu is a 1 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: 1FM Activity: Mitogen-activated protein kinase kinase, with EC number 2.7.12.2 Resources: FirstGlance, OCA, RCSB, PDBsum Function [MP2K7_HUMAN] Dual specificity protein kinase which acts as an essential component of the MAP kinase signal transduction pathway. Essential component of the stress-activated protein kinase/c-Jun N-terminal kinase (SAP/JNK) signaling pathway. With MAP2K4/MKK4, is the one of the only known kinase to directly activate the stress-activated protein kinase/c-Jun N-terminal kinases MAPK8/JNK1, MAPK9/JNK2 and MAPK10/JNK3. MAP2K4/MKK4 and MAP2K7/MKK7 both activate the JNKs by phosphorylation, but they differ in their preference for the phosphorylation site in the Thr-Pro-Tyr motif. MAP2K4/MKK4 shows preference for phosphorylation of the Tyr residue and MAP2K7/MKK7 for the Thr residue. The monophosphorylation of JNKs on the Thr residue is sufficient to increase JNK activity indicating that MAP2K7/MKK7 is important to trigger JNK activity, while the additional phosphorylation of the Tyr residue by MAP2K4/MKK4 ensures optimal JNK activation. Has a specific role in JNK signal transduction pathway activated by proinflammatory cytokines. The MKK/JNK signaling pathway is also involved in mitochondrial death signaling pathway, including the release cytochrome c, leading to apoptosis. [:] Publication Abstract from PubMed 5Z-7-Oxozeaenol (5Z7O) is a covalent bonding inhibitor against the several protein kinases (e.g., ERK2 and TAK1) that possess a free cysteine at the gatekeeper-2 position. In addition to this cysteine, MAP2K7 has three other cysteine residues that are candidate for covalent bonding by the inhibitor 5Z7O. The crystal structure of the MAP2K7/5Z7O complex revealed that the inhibitor binds to MAP2K7 at a cysteine residue located at the end of the hinge region and not at the gatekeeper-2 residue. The structural insights into the interaction of 5Z7O with MAP2K7 should aid the development of 5Z7O derivatives with improved potency and selectivity. 5Z-7-Oxozeaenol covalently binds to MAP2K7 at Cys218 in an unprecedented manner.,Sogabe Y, Matsumoto T, Hashimoto T, Kirii Y, Sawa M, Kinoshita T Bioorg Med Chem Lett. 2014 Dec 13. pii: S0960-894X(14)01308-0. doi:, 10.1016/j.bmcl.2014.12.011. PMID:25529738 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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