2WWP

Crystal structure of the human lipocalin-type prostaglandin D synthase

2WWP の概要

• エントリーDOI: 10.2210/pdb2wwp/pdb
• 分子名称: PROSTAGLANDIN-H2 D-ISOMERASE, CHLORIDE ION, THIOCYANATE ION, ... (4 entities in total)
• 機能のキーワード: cytoplasm, transport, endoplasmic reticulum, fatty acid biosynthesis, golgi apparatus, beta-trace protein, isomerase, lipid synthesis
• 由来する生物種: HOMO SAPIENS (HUMAN)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 39683.36

構造登録者

Roos, A.K.,Tresaugues, L.,Arrowsmith, C.H.,Berglund, H.,Bountra, C.,Collins, R.,Edwards, A.M.,Flodin, S.,Flores, A.,Graslund, S.,Hammarstrom, M.,Johansson, A.,Johansson, I.,Kallas, A.,Karlberg, T.,Kotyenova, T.,Kotzch, A.,Kraulis, P.,Markova, N.,Moche, M.,Nielsen, T.K.,Nyman, T.,Persson, C.,Schuler, H.,Schutz, P.,Siponen, M.I.,Svensson, L.,Thorsell, A.G.,Van Den Berg, S.,Wahlberg, E.,Weigelt, J.,Welin, M.,Wisniewska, M.,Nordlund, P.,Structural Genomics Consortium (SGC) (登録日: 2009-10-26, 公開日: 2010-01-12, 最終更新日: 2023-12-20)

主引用文献

Lim, S.M.,Chen, D.,Teo, H.,Roos, A.,Jansson, A.E.,Nyman, T.,Tresaugues, L.,Pervushin, K.,Nordlund, P.
Structural and Dynamic Insights Into Substrate Binding and Catalysis of Human Lipocalin Prostaglandin D Synthase.
J.Lipid Res., 54:1630-, 2013

PubMed Abstract: Lipocalin prostaglandin D synthase (L-PGDS) regulates synthesis of an important inflammatory and signaling mediator, prostaglandin D2 (PGD2). Here, we used structural, biophysical, and biochemical approaches to address the mechanistic aspects of substrate entry, catalysis, and product exit of this enzyme. Structure of human L-PGDS was solved in a complex with a substrate analog (SA) and in ligand-free form. Its catalytic Cys 65 thiol group was found in two different conformations, each making a distinct hydrogen bond network to neighboring residues. These help in elucidating the mechanism of the cysteine nucleophile activation. Electron density for ligand observed in the active site defined the substrate binding regions, but did not allow unambiguous fitting of the SA. To further understand ligand binding, we used NMR spectroscopy to map the binding sites and to show the dynamics of protein-substrate and protein-product interactions. A model for ligand binding at the catalytic site is proposed, showing a second binding site involved in ligand exit and entry. NMR chemical shift perturbations and NMR resonance line-width alterations (observed as changes of intensity in two-dimensional cross-peaks in [¹H,¹⁵N]-transfer relaxation optimization spectroscopy) for residues at the Ω loop (A-B loop), E-F loop, and G-H loop besides the catalytic sites indicate involvement of these residues in ligand entry/egress.

PubMed: 23526831
DOI: 10.1194/JLR.M035410

実験手法

X-RAY DIFFRACTION (2 Å)