4JC7: Human Ltc4 Synthase In Complex With Product Analogs - Implications For Enzyme Catalysis

Citation:
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.
PDB ID: 4JC7Download
MMDB ID: 116371
PDB Deposition Date: 2013/2/21
Updated in MMDB: 2014/03
Experimental Method:
x-ray diffraction
Resolution: 2.7  Å
Source Organism:
Similar Structures:
Biological Unit for 4JC7: trimeric; determined by author and by software (PISA)
Molecular Components in 4JC7
Label Count Molecule
Proteins (3 molecules)
3
Leukotriene C4 Synthase(Gene symbol: LTC4S)
Molecule annotation
Chemicals (28 molecules)
1
7
2
3
3
3
4
12
5
3
* Click molecule labels to explore molecular sequence information.

Citing MMDB
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