4JRZ

Human LTC4 synthase in complex with product analogs - implications for enzyme catalysis

4JRZ の概要

• エントリーDOI: 10.2210/pdb4jrz/pdb
• 関連するPDBエントリー: 2UUH 2UUI
• 分子名称: Leukotriene C4 synthase, NICKEL (II) ION, SULFATE ION, ... (7 entities in total)
• 機能のキーワード: leukotriene c4 synthase, product analogs, lipid biosynthesis, lyase
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Nucleus outer membrane; Multi-pass membrane protein: Q16873
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 19573.67

構造登録者

Niegowski, D.,Rinaldo-Matthis, A.,Haeggstrom, J.Z. (登録日: 2013-03-22, 公開日: 2014-01-01, 最終更新日: 2023-09-20)

主引用文献

Niegowski, D.,Kleinschmidt, T.,Olsson, U.,Ahmad, S.,Rinaldo-Matthis, A.,Haeggstrom, J.Z.
Crystal Structures of Leukotriene C4 Synthase in Complex with Product Analogs: IMPLICATIONS FOR THE ENZYME MECHANISM.
J.Biol.Chem., 289:5199-5207, 2014

PubMed Abstract: Leukotriene (LT) C4 synthase (LTC4S) catalyzes the conjugation of the fatty acid LTA4 with the tripeptide GSH to produce LTC4, the parent compound of the cysteinyl leukotrienes, important mediators of asthma. Here we mutated Trp-116 in human LTC4S, a residue proposed to play a key role in substrate binding, into an Ala or Phe. Biochemical and structural characterization of these mutants along with crystal structures of the wild type and mutated enzymes in complex with three product analogs, viz. S-hexyl-, 4-phenyl-butyl-, and 2-hydroxy-4-phenyl-butyl-glutathione, provide new insights to binding of substrates and product, identify a new conformation of the GSH moiety at the active site, and suggest a route for product release, aided by Trp-116.

PubMed: 24366866
DOI: 10.1074/jbc.M113.534628

実験手法

X-RAY DIFFRACTION (2.4 Å)