9USA

Whole structure of C44S/C47S double mutant form of human prostamide/prostaglandin F synthase (PGFS)

9USA の概要

• エントリーDOI: 10.2210/pdb9usa/pdb
• 分子名称: Prostamide/prostaglandin F synthase (2 entities in total)
• 機能のキーワード: thioredoxin fold, cxxc motif, pgfs, oxidoreductase
• 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: 21216.40

構造登録者

Cheon, S.W.,Yen, N.T.K.,Han, B.W. (登録日: 2025-05-01, 公開日: 2026-04-01)

主引用文献

Cheon, S.W.,Nguyen, Y.T.K.,Kang, J.M.,Yu, Y.,Heo, Y.,Kim, H.S.,Han, B.W.
Structural and Biophysical Analyses of Human Prostamide/Prostaglandin F Synthase with Two Active Form-Mimicking Mutations.
Biomolecules, 16:-, 2026

PubMed Abstract: Human prostamide/prostaglandin F synthase (PGFS) catalyzes the NADPH-dependent conversion of prostaglandin H (PGH2) to prostaglandin Fα that plays a key role in regulating intraocular pressure and labor. Despite its physiological importance, structural and biochemical information of the human PGFS has been limited because of difficulties in obtaining sufficient quality of PGFS wild-type crystal and short half-life of PGH2. Here, we report the crystal structure of human PGFS with two active site mutations, C44S/C47S double mutant (DM), which mimics the reduced active form of the CXXC motif of human PGFS. Structural analysis revealed that PGFS DM adopts a typical thioredoxin (Trx)-like fold. Analysis of B-factors and MD simulations reveals that Tyr108-Asp124 is an intrinsically flexible region, devoid of any stabilizing crystal contacts. Unlike canonical Trx-like proteins, Pro167 in PGFS adopts a trans-conformation, inducing a specific Arg40 side chain localization that creates a positive charge near the CXXC motif. Activation of PGFS by reduction of disulfide bond in the CXXC motif enhanced the thermal stability via core stabilization, yet an unexpected increase in the structural disorder was detected with CD spectroscopy, especially upon ligand binding. These findings collectively establish PGFS as a structurally distinct and redox-regulated enzyme. Our results provide novel molecular insights into PGFS as an underexplored but promising therapeutic target.

PubMed: 41750332
DOI: 10.3390/biom16020262

実験手法

X-RAY DIFFRACTION (2.3 Å)