3n8m
Crystal Structure of the Grb2 SH2 Domain in Complex with An Acyclic Ligand Having the Sequence pYVNVPCrystal Structure of the Grb2 SH2 Domain in Complex with An Acyclic Ligand Having the Sequence pYVNVP
Structural highlights
Publication Abstract from PubMedThe 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. Thermodynamic and Structural Effects of Macrocyclization as a Constraining Method in Protein-Ligand Interactions.,Delorbe JE, Clements JH, Whiddon BB, Martin SF ACS Med Chem Lett. 2010 Nov 11;1(8):448-452. PMID:21116482[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
|
| ||||||||||||||||||||||