5B4W

Crystal structure of Plexin inhibitor complex

5B4W の概要

• エントリーDOI: 10.2210/pdb5b4w/pdb
• 分子名称: Plexin-B1, Synthesized cyclic peptide, 2-acetamido-2-deoxy-beta-D-glucopyranose, ... (4 entities in total)
• 機能のキーワード: plexin, inhibitor, signaling protein
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 12
• 化学式量合計: 385265.66

構造登録者

Matsunaga, Y.,Kitago, Y.,Arimori, T.,Takagi, J. (登録日: 2016-04-19, 公開日: 2016-12-28, 最終更新日: 2024-11-06)

主引用文献

Matsunaga, Y.,Bashiruddin, N.K.,Kitago, Y.,Takagi, J.,Suga, H.
Allosteric Inhibition of a Semaphorin 4D Receptor Plexin B1 by a High-Affinity Macrocyclic Peptide
Cell Chem Biol, 23:1341-1350, 2016

PubMed Abstract: Semaphorin axonal guidance factors are multifunctional proteins that play important roles in immune response, cancer cell proliferation, and organogenesis, making semaphorins and their signaling receptor plexins important drug targets for various diseases. However, the large and flat binding surface of the semaphorin-plexin interaction interface is difficult to target by traditional small-molecule drugs. Here, we report the discovery of a high-affinity plexin B1 (PlxnB1)-binding macrocyclic peptide, PB1m6 (K = 3.5 nM). PB1m6 specifically inhibited the binding of physiological ligand semaphorin 4D (Sema4D) in vitro and completely suppressed Sema4D-induced cell collapse. Structural studies revealed that PB1m6 binds at a groove between the fifth and sixth blades of the sema domain in PlxnB1 distant from the Sema4D-binding site, indicating the non-competitive and allosteric nature of the inhibitory activity. The discovery of this novel allosteric site can potentially be used to target plexin family proteins for the development of drugs that modulate semaphorin and plexin signaling.

PubMed: 27984026
DOI: 10.1016/j.chembiol.2016.09.015

実験手法

X-RAY DIFFRACTION (2.6 Å)