3N7Y

Crystal Structure of the Grb2 SH2 Domain in Complex with a 20-Membered Macrocyclic Ligand Having the Sequence pYVNV

3N7Y の概要

• エントリーDOI: 10.2210/pdb3n7y/pdb
• 関連するPDBエントリー: 1BM2 3N84
• 分子名称: Growth factor receptor-bound protein 2, 20-membered peptide-like macrocyclic ligand (3 entities in total)
• 機能のキーワード: ligand preorganization, macrocycles, macrocyclic ligands, golgi apparatus, host-virus interaction, phosphoprotein, protein binding-peptide complex, protein binding/peptide
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Golgi apparatus (By similarity): P62993
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 36443.23

構造登録者

Whiddon, B.B.,Clements, J.H.,Martin, S.F. (登録日: 2010-05-27, 公開日: 2011-01-12, 最終更新日: 2024-10-16)

主引用文献

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

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: 21116482
DOI: 10.1021/ml100142y

実験手法

X-RAY DIFFRACTION (2.02 Å)