2IAG

Crystal structure of human prostacyclin synthase

2IAG の概要

• エントリーDOI: 10.2210/pdb2iag/pdb
• 分子名称: Prostacyclin synthase, PROTOPORPHYRIN IX CONTAINING FE, SODIUM ION, ... (4 entities in total)
• 機能のキーワード: prostacyclin synthase, class iii cytochorme p450, hemoprotein, cyp8a1, isomerase
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Endoplasmic reticulum membrane; Single-pass membrane protein: Q16647
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 111966.75

構造登録者

Chiang, C.-W.,Yeh, H.-C.,Wang, L.-H.,Chan, N.-L. (登録日: 2006-09-08, 公開日: 2006-10-10, 最終更新日: 2024-03-13)

主引用文献

Chiang, C.-W.,Yeh, H.-C.,Wang, L.-H.,Chan, N.-L.
Crystal Structure of the Human Prostacyclin Synthase
J.Mol.Biol., 364:266-274, 2006

PubMed Abstract: Prostacyclin synthase (PGIS) catalyzes an isomerization of prostaglandin H(2) to prostacyclin, a potent mediator of vasodilation and anti-platelet aggregation. Here, we report the crystal structure of human PGIS at 2.15 A resolution, which represents the first three-dimensional structure of a class III cytochrome P450. While notable sequence divergence has been recognized between PGIS and other P450s, PGIS exhibits the typical triangular prism-shaped P450 fold with only moderate structural differences. The conserved acid-alcohol pair in the I helix of P450s is replaced by residues G286 and N287 in PGIS, but the distinctive disruption of the I helix and the presence of a nearby water channel remain conserved. The side-chain of N287 appears to be positioned to facilitate the endoperoxide bond cleavage, suggesting a functional conservation of this residue in O-O bond cleavage. A combination of bent I helix and tilted B' helix creates a channel extending from the heme distal pocket, which seemingly allows binding of various ligands; however, residue W282, placed in this channel at a distance of 8.4 A from the iron with its indole side-chain lying parallel with the porphyrin plane, may serve as a threshold to exclude most ligands from binding. Additionally, a long "meander" region protruding from the protein surface may impede electron transfer. Although the primary sequence of the PGIS cysteine ligand loop diverges significantly from the consensus, conserved tertiary structure and hydrogen bonding pattern are observed for this region. The substrate-binding model was constructed and the structural basis for prostacyclin biosynthesis is discussed.

PubMed: 17020766
DOI: 10.1016/j.jmb.2006.09.039

実験手法

X-RAY DIFFRACTION (2.15 Å)