5DX3: Estrogen Receptor Alpha Ligand Binding Domain Y537S Mutant in Complex with Stapled Peptide SRC2-P3 and Estradiol

"Stapled" peptides are typically designed to replace two non-interacting residues with a constraining, olefinic staple. To mimic interacting leucine and isoleucine residues, we have created new amino acids that incorporate a methyl group in the gamma-position of the stapling amino acid S5. We have incorporated them into a sequence derived from steroid receptor coactivator 2, which interacts with estrogen receptor alpha. The best peptide (IC50 =89 nm) replaces isoleucine 689 with an S-gamma-methyl stapled amino acid, and has significantly higher affinity than unsubstituted peptides (390 and 760 nm). Through X-ray crystallography and molecular dynamics studies, we show that the conformation taken up by the S-gamma-methyl peptide minimizes the syn-pentane interactions between the alpha- and gamma-methyl groups.
PDB ID: 5DX3Download
MMDB ID: 140723
PDB Deposition Date: 2015/9/23
Updated in MMDB: 2017/09
Experimental Method:
x-ray diffraction
Resolution: 2.0903  Å
Source Organism:
Similar Structures:
Biological Unit for 5DX3: dimeric; determined by author and by software (PISA)
Molecular Components in 5DX3
Label Count Molecule
Proteins (2 molecules)
Estrogen Receptor(Gene symbol: ESR1)
Molecule annotation
Stapled Peptide Src2-p3(Gene symbol: NCOA2)
Molecule annotation
Chemicals (2 molecules)
* Click molecule labels to explore molecular sequence information.

Citing MMDB