2CZU

lipocalin-type prostaglandin D synthase

2CZU の概要

• エントリーDOI: 10.2210/pdb2czu/pdb
• 関連するPDBエントリー: 2CZT
• 分子名称: Prostaglandin-H2 D-isomerase (2 entities in total)
• 機能のキーワード: lipocalin, lpgds_p212121 native, riken structural genomics/proteomics initiative, rsgi, structural genomics, isomerase
• 由来する生物種: Mus musculus (house mouse)
• 細胞内の位置: Rough endoplasmic reticulum (By similarity): O09114
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 37235.72

構造登録者

Kumasaka, T.,Irikura, D.,Ago, H.,Aritake, K.,Yamamoto, M.,Inoue, T.,Miyano, M.,Urade, Y.,Hayaishi, O.,RIKEN Structural Genomics/Proteomics Initiative (RSGI) (登録日: 2005-07-17, 公開日: 2006-10-03, 最終更新日: 2024-10-09)

主引用文献

Kumasaka, T.,Aritake, K.,Ago, H.,Irikura, D.,Tsurumura, T.,Yamamoto, M.,Miyano, M.,Urade, Y.,Hayaishi, O.
Structural basis of the catalytic mechanism operating in open-closed conformers of lipocalin type prostaglandin D synthase.
J.Biol.Chem., 284:22344-22352, 2009

PubMed Abstract: Lipocalin type prostaglandin D synthase (L-PGDS) is a multifunctional protein acting as a somnogen (PGD2)-producing enzyme, an extracellular transporter of various lipophilic ligands, and an amyloid-beta chaperone in human cerebrospinal fluid. In this study, we determined the crystal structures of two different conformers of mouse L-PGDS, one with an open cavity of the beta-barrel and the other with a closed cavity due to the movement of the flexible E-F loop. The upper compartment of the central large cavity contains the catalytically essential Cys65 residue and its network of hydrogen bonds with the polar residues Ser45, Thr67, and Ser81, whereas the lower compartment is composed of hydrophobic amino acid residues that are highly conserved among other lipocalins. SH titration analysis combined with site-directed mutagenesis revealed that the Cys65 residue is activated by its interaction with Ser45 and Thr67 and that the S45A/T67A/S81A mutant showed less than 10% of the L-PGDS activity. The conformational change between the open and closed states of the cavity indicates that the mobile calyx contributes to the multiligand binding ability of L-PGDS.

PubMed: 19546224
DOI: 10.1074/jbc.M109.018341

実験手法

X-RAY DIFFRACTION (2.1 Å)