9TA5

PITP covalently bound to microcolin H

これはPDB形式変換不可エントリーです。

9TA5 の概要

• エントリーDOI: 10.2210/pdb9ta5/pdb
• 関連するBIRD辞書のPRD_ID: PRD_002597
• 分子名称: Phosphatidylinositol transfer protein alpha isoform, Microcolin H, IMIDAZOLE, ... (5 entities in total)
• 機能のキーワード: pitp, microcolin h, lipid transport
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 32805.16

構造登録者

Eisenreichova, A.,Klima, M.,Boura, E. (登録日: 2025-11-18, 公開日: 2026-02-04, 最終更新日: 2026-03-11)

主引用文献

Eisenreichova, A.,Klima, M.,Balla, T.,Boura, E.
Phosphatidylinositol transfer protein alpha binds microcolins in its open conformation.
Acta Crystallogr D Struct Biol, 82:246-252, 2026

PubMed Abstract: Phosphatidylinositol transfer proteins (PITPs) are essential lipid-binding proteins that regulate phosphoinositide signaling, membrane trafficking and autophagy through the transport of phosphatidylinositol and other phospholipids between intracellular membranes. Microcolin compounds have been identified as selective inhibitors of class I PITPs, revealing important roles of PITPs in Hippo signaling and autophagy. Here, we report the crystal structure of human PITPα in complex with microcolin H at 2.0 Å resolution. The structure enables a detailed description of the interaction between microcolin H and the lipid-binding cavity. Besides the expected covalent bond to the Cys94 residue, the structure also reveals an extensive network of hydrogen bonds, water bridges and hydrophobic interactions. Importantly, PITPα remains in the open conformation upon binding to microcolin H. Quantitative cavity analysis confirms that the microcolin-bound structure adopts a volume comparable to that of the unliganded PITPα and is markedly larger than that of the lipid-bound state. These findings demonstrate that microcolins selectively trap PITPα in an open conformation and provide a structural basis for their inhibitory mechanism. Furthermore, our results show that ligand binding can profoundly change protein conformation, which underscores the limitation of docking experiments.

PubMed: 41700428
DOI: 10.1107/S2059798326000872

実験手法

X-RAY DIFFRACTION (2.1 Å)