4p9v

Grb2 SH2 complexed with a pTyr-Ac6cN-Asn tripeptide

spinqualitylabelsall models 4p9v, resolution 1.64Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4p9v is a 2 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: CL NonStd Res: 02K, NH2, PHQ, PTR Related: 3s8o, 4p9z 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 In order to probe the energetics associated with a putative cation-pi interaction, thermodynamic parameters are determined for complex formation between the Grb2 SH2 domain and tripeptide derivatives of RCO-pTyr-Ac6c-Asn wherein the R group is varied to include different alkyl, cycloalkyl, and aryl groups. Although an indole ring is reputed to have the strongest interaction with a guanidinium ion, binding free energies, DeltaG degrees , for derivatives of RCO-pTyr-Ac6c-Asn bearing cyclohexyl and phenyl groups were slightly more favorable than their indolyl analog. Crystallographic analysis of two complexes reveals that test ligands bind in similar poses with the notable exception of the relative orientation and proximity of the phenyl and indolyl rings relative to an arginine residue of the domain. These spatial orientations are consistent with those observed in other cation-pi interactions, but there is no net energetic benefit to such an interaction in this biological system. Accordingly, although cation-pi interactions are well documented as important noncovalent forces in molecular recognition, the energetics of such interactions may be mitigated by other nonbonded interactions and solvation effects in protein-ligand associations. Protein-ligand interactions: Probing the energetics of a putative cation-pi interaction.,Myslinski JM, Clements JH, Martin SF Bioorg Med Chem Lett. 2014 Jul 15;24(14):3164-7. doi: 10.1016/j.bmcl.2014.04.114., Epub 2014 May 9. PMID:24856058 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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