1IYI

Crystal structure of hematopoietic prostaglandin D synthase

1IYI の概要

• エントリーDOI: 10.2210/pdb1iyi/pdb
• 関連するPDBエントリー: 1IYH
• 分子名称: HEMATOPOIETIC PROSTAGLANDIN D SYNTHASE, GLUTATHIONE, CALCIUM ION, ... (4 entities in total)
• 機能のキーワード: hematopoietic prostaglandin d synthase, pgds, gst, sigma-class gst, ligase, isomerase
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Cytoplasm: O60760
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 94336.37

構造登録者

Inoue, T. (登録日: 2002-08-26, 公開日: 2003-04-08, 最終更新日: 2023-12-27)

主引用文献

Inoue, T.,Irikura, D.,Okazaki, N.,Kinugasa, S.,Matsumura, H.,Uodome, N.,Yamamoto, M.,Kumasaka, T.,Miyano, M.,Kai, Y.,Urade, Y.
Mechanism of metal activation of human hematopoietic prostaglandin D synthase
NAT.STRUCT.BIOL., 10:291-296, 2003

PubMed Abstract: Here we report the crystal structures of human hematopoietic prostaglandin (PG) D synthase bound to glutathione (GSH) and Ca2+ or Mg2+. Using GSH as a cofactor, prostaglandin D synthase catalyzes the isomerization of PGH2 to PGD2, a mediator for allergy response. The enzyme is a homodimer, and Ca2+ or Mg2+ increases its activity to approximately 150% of the basal level, with half maximum effective concentrations of 400 microM for Ca2+ and 50 microM for Mg2+. In the Mg2+-bound form, the ion is octahedrally coordinated by six water molecules at the dimer interface. The water molecules are surrounded by pairs of Asp93, Asp96 and Asp97 from each subunit. Ca(2+) is coordinated by five water molecules and an Asp96 from one subunit. The Asp96 residue in the Ca2+-bound form makes hydrogen bonds with two guanidium nitrogen atoms of Arg14 in the GSH-binding pocket. Mg2+ alters the coordinating water structure and reduces one hydrogen bond between Asp96 and Arg14, thereby changing the interaction between Arg14 and GSH. This effect explains a four-fold reduction in the K(m) of the enzyme for GSH. The structure provides insights into how Ca2+ or Mg2+ binding activates human hematopoietic PGD synthase.

PubMed: 12627223
DOI: 10.1038/nsb907

実験手法

X-RAY DIFFRACTION (1.8 Å)