7mph | pdb_00007mph

GRB2 SH2 Domain with Compound 7

spinqualitylabelsall models 7mph, resolution 2.00Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 7mph is a 6 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 2Å Ligands: EDO, SO4, ZLY Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function GRB2_HUMAN Adapter protein that provides a critical link between cell surface growth factor receptors and the Ras signaling pathway. Isoform 2 does not bind to phosphorylated epidermal growth factor receptor (EGFR) but inhibits EGF-induced transactivation of a RAS-responsive element. Isoform 2 acts as a dominant negative protein over GRB2 and by suppressing proliferative signals, may trigger active programmed cell death. Publication Abstract from PubMed A monocarboxylic inhibitor was designed and synthesized to disrupt the protein-protein interaction (PPI) between GRB2 and phosphotyrosine-containing proteins. Biochemical characterizations show compound 7 binds with the Src homology 2 (SH2) domain of GRB2 and is more potent than EGFR1068 phosphopeptide 14-mer. X-ray crystallographic studies demonstrate compound 7 occupies the GRB2 binding site for phosphotyrosine-containing sequences and reveal key structural features for GRB2-inhibitor binding. This compound with a -1 formal charge offers a new direction for structural optimization to generate cell-permeable inhibitors for this key protein target of the aberrant Ras-MAPK signaling cascade. Synthesis and structural characterization of a monocarboxylic inhibitor for GRB2 SH2 domain.,Xiao T, Sun L, Zhang M, Li Z, Haura EB, Schonbrunn E, Ji H Bioorg Med Chem Lett. 2021 Sep 7;51:128354. doi: 10.1016/j.bmcl.2021.128354. PMID:34506932 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Growth factor receptor-bound proteins 3D structures

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