3N84
Crystal Structure of the Grb2 SH2 Domain in Complex with a 23-Membered Macrocyclic Ligand Having the Sequence pYVNVP
Summary for 3N84
| Entry DOI | 10.2210/pdb3n84/pdb |
| Related | 1BM2 3N7Y |
| Descriptor | Growth factor receptor-bound protein 2, 23-membered peptide-like macrocyclic ligand, CHLORIDE ION, ... (6 entities in total) |
| Functional Keywords | ligand preorganization, macrocycles, macrocyclic ligands, golgi apparatus, host-virus interaction, phosphoprotein, protein binding-peptide complex, protein binding/peptide |
| Biological source | Homo sapiens (human) |
| Cellular location | Golgi apparatus (By similarity): P62993 |
| Total number of polymer chains | 12 |
| Total formula weight | 83891.99 |
| Authors | Clements, J.H.,Martin, S.F. (deposition date: 2010-05-27, release date: 2011-01-12, Last modification date: 2024-10-16) |
| Primary citation | Delorbe, J.E.,Clements, J.H.,Whiddon, B.B.,Martin, S.F. Thermodynamic and Structural Effects of Macrocyclization as a Constraining Method in Protein-Ligand Interactions. ACS MED.CHEM.LETT., 1:448-452, 2010 Cited by PubMed Abstract: The thermodynamic and structural effects of macrocyclization as a tactic for stabilizing the biologically-active conformation of Grb2 SH2 binding peptides were investigated using isothermal titration calorimetry and x-ray crystallography. 23-Membered macrocycles containing the sequence pYVN were slightly more potent than their linear controls; however, preorganization did not necessarily eventuate in a more favorable binding entropy. Structures of complexes of macrocycle 7 and its acyclic control 8 are similar except for differences in relative orientations of corresponding atoms in the linking moieties of 7 and 8. There are no differences in the number of direct or water-mediated protein-ligand contacts that might account for the less favorable binding enthalpy of 7; however, an intramolecular hydrogen bond between the pY and pY+3 residues in 8 that is absent in 7 may be a factor. These studies highlight the difficulties associated with correlating energetics and structure in protein-ligand interactions. PubMed: 21116482DOI: 10.1021/ml100142y PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2 Å) |
Structure validation
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