9T0A

X-ray structure of the complex between the catalytic domain of CDC25B C473S and 3-O-methylfluorescein phosphate (3-OMFP)

これはPDB形式変換不可エントリーです。

9T0A の概要

• エントリーDOI: 10.2210/pdb9t0a/pdb
• 関連するPDBエントリー: 9T09
• 分子名称: M-phase inducer phosphatase 2, [(1~{R})-6'-methoxy-3-oxidanylidene-spiro[2-benzofuran-1,9'-xanthene]-3'-yl] dihydrogen phosphate, [(1~{S})-6'-methoxy-3-oxidanylidene-spiro[2-benzofuran-1,9'-xanthene]-3'-yl] dihydrogen phosphate, ... (5 entities in total)
• 機能のキーワード: cdc25b, catalytic domain, phosphatase, cell division cycle 25b, substrate, 3-o-methylfluorescein phosphate, hydrolase
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 23954.25

構造登録者

Troisi, R.,Napolitano, V.,Sica, F. (登録日: 2025-10-16, 公開日: 2026-03-11, 最終更新日: 2026-04-08)

主引用文献

Troisi, R.,Rullo, R.,Napolitano, V.,Popowicz, G.M.,De Vendittis, E.,Sica, F.
The Binding of 3-O-Methylfluorescein Phosphate to the Catalytic Domain of the Human CDC25B Phosphatase: A Structural Investigation.
Chembiochem, 27:e202600010-e202600010, 2026

PubMed Abstract: The molecular mechanisms by which the human CDC25B activates the CDK1/cyclin B complex in the cell cycle, as well as how it can be inhibited by synthetic inhibitors at the atomic level, are still under investigation. Valuable insights have been gained from the molecular structure here-described, which captures for the first time the interaction between the C-terminal domain of the inactive mutant CDC25B C473S (CDC25B-S) and the commonly used synthetic substrate 3-O-methylfluorescein phosphate (3-OMFP). Crystallographic studies reveal that 3-OMFP engages multiple residues within the active site and the adjacent "swimming pool" of CDC25B-S, establishing specific interactions and prompting local adjustments in this region. These structural features explain the increased resistance to thermal denaturation of CDC25B-S observed through circular dichroism measurements upon substrate binding. The structural changes induced by 3-OMFP lead to a conformation comparable to that of CDC25A bound to its substrate, the CDK2/cyclin A complex. These findings qualify 3-OMFP as a promising starting model for the rational design of selective competitive inhibitors of CDC25B having reduced off-target effects.

PubMed: 41906666
DOI: 10.1002/cbic.202600010

実験手法

X-RAY DIFFRACTION (2.04 Å)