6q2x | pdb_00006q2x

TEAD4 (216-434) COMPLEXED WITH YAP PEPTIDE (60-100) AND MYRISTOATE (COVALENTLY BOUND) AT 2.1A (P41212 CRYSTAL FORM)

spinqualitylabelsall models 6q2x, resolution 2.10Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6q2x 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 2.1Å Ligands: GOL, MYR Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function TEAD4_HUMAN Transcription factor which plays a key role in the Hippo signaling pathway, a pathway involved in organ size control and tumor suppression by restricting proliferation and promoting apoptosis. The core of this pathway is composed of a kinase cascade wherein MST1/MST2, in complex with its regulatory protein SAV1, phosphorylates and activates LATS1/2 in complex with its regulatory protein MOB1, which in turn phosphorylates and inactivates YAP1 oncoprotein and WWTR1/TAZ. Acts by mediating gene expression of YAP1 and WWTR1/TAZ, thereby regulating cell proliferation, migration and epithelial mesenchymal transition (EMT) induction. Binds specifically and non-cooperatively to the Sph and GT-IIC 'enhansons' (5'-GTGGAATGT-3') and activates transcription. Binds to the M-CAT motif. Publication Abstract from PubMed The YAP-TEAD protein-protein interaction is a potential therapeutic target to treat cancers in which the Hippo signaling pathway is deregulated. However, the extremely large surface of interaction between the two proteins presents a formidable challenge for a small molecule interaction disrupter approach. We have accomplished progress towards showing the feasibility of this approach by the identification of a 15-mer peptide able to potently (nanomolar range) disrupt the YAP-TEAD interaction by targeting only one of the two important sites of interaction. This peptide, incorporating non-natural amino acids selected by structure-based design, is derived from the Omega-loop sequence 85-99 of YAP. Structure-based design of potent linear peptide inhibitors of the YAP-TEAD protein-protein interaction derived from the YAP omega-loop sequence.,Furet P, Salem B, Mesrouze Y, Schmelzle T, Lewis I, Kallen J, Chene P Bioorg Med Chem Lett. 2019 Jun 18. pii: S0960-894X(19)30402-0. doi:, 10.1016/j.bmcl.2019.06.022. PMID:31235263 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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