4MZJ

Crystal Structure of MTIP from Plasmodium falciparum in complex with pGly[801,805], a stapled myoA tail peptide

4MZJ の概要

• エントリーDOI: 10.2210/pdb4mzj/pdb
• 関連するPDBエントリー: 4AOM 4MZK 4MZL
• 関連するBIRD辞書のPRD_ID: PRD_001186
• 分子名称: Myosin A tail domain interacting protein, Myosin-A (3 entities in total)
• 機能のキーワード: actomyosin motor, stapled peptides, protein binding-inhibitor complex, protein binding/inhibitor
• 由来する生物種: Plasmodium falciparum; 詳細
• 細胞内の位置: Cell membrane ; Peripheral membrane protein ; Cytoplasmic side : Q8IDR3
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 18661.95

構造登録者

Douse, C.H.,Garnett, J.A.,Maas, S.J.,Cota, E.,Tate, E.W. (登録日: 2013-09-30, 公開日: 2013-11-06, 最終更新日: 2024-11-20)

主引用文献

Douse, C.H.,Maas, S.J.,Thomas, J.C.,Garnett, J.A.,Sun, Y.,Cota, E.,Tate, E.W.
Crystal Structures of Stapled and Hydrogen Bond Surrogate Peptides Targeting a Fully Buried Protein-Helix Interaction.
Acs Chem.Biol., 8:506-512, 2014

PubMed Abstract: Constrained α-helical peptides are an exciting class of molecule designed to disrupt protein-protein interactions (PPIs) at a surface-exposed helix binding site. Complexes that engage more than one helical face account for over a third of structurally characterized helix PPIs, including several examples where the helix is fully buried. However, no constrained peptides have been reported that have targeted this class of interaction. We report the design of stapled and hydrogen bond surrogate (HBS) peptides mimicking the helical tail of the malaria parasite invasion motor myosin (myoA), which presents polar and hydrophobic functionality on all three faces in binding its partner, myoA tail interacting protein (MTIP), with high affinity. The first structures of these different constrained peptides bound to the same target are reported, enabling a direct comparison between these constraints and between staples based on monosubstituted pentenyl glycine (pGly) and disubstituted pentenyl alanine (pAla). Importantly, installation of these constraints does not disrupt native interactions in the buried site, so the affinity of the wild-type peptide is maintained.

PubMed: 25084543
DOI: 10.1021/cb500271c

実験手法

X-RAY DIFFRACTION (1.474 Å)