4JCZ

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

Summary for 4JCZ

• Entry DOI: 10.2210/pdb4jcz/pdb
• Related: 2UUH 2UUI 4JC7
• Descriptor: Leukotriene C4 synthase, NICKEL (II) ION, SULFATE ION, ... (7 entities in total)
• Functional Keywords: leukotriene c4 synthase, product analogs, lipid biosynthesis, lyase
• Biological source: Homo sapiens (human)
• Cellular location: Nucleus outer membrane; Multi-pass membrane protein: Q16873
• Total number of polymer chains: 1
• Total formula weight: 19495.32

Authors

Niegowski, D.,Rinaldo-Matthis, A.,Haeggstrom, J.Z. (deposition date: 2013-02-22, release date: 2014-01-01, Last modification date: 2023-09-20)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2.75 Å)