Leukotriene C(4) synthase.
LTC(4) synthase conjugates LTA(4) with glutathione (GSH) to form LTC(4), the parent compound of the cysteinyl leukotrienes. LTC(4) synthase is a membrane protein that functions as a non-covalent homodimer of two 18-kDa polypeptides. The enzymatic activity of LTC(4) synthase is augmented by Mg(2+) and inhibited by Co(2+) and the FLAP inhibitor MK-886. The K(m) and V(max) values of human LTC(4) synthase are 3.6 microM and 1.3 micromol/mg/min for LTA(4) and 1.6 mM and 2.7 micromol/mg/min for GSH, respectively. The deduced amino acid sequence and the predicted secondary structure of LTC(4) synthase share significant homology to FLAP, mGST-2, and mGST-3. Site-directed mutagenesis of LTC(4) synthase suggests that Arg-51 is involved in opening the epoxide ring of LTA(4) and Tyr-93 in GSH thiolate anion formation during catalytic conjugation. LTC(4) synthase is a TATA-less gene whose transcription involved both cell- and non-specific regulatory elements. LTC(4) synthase gene disrupted mice grow normally, and are attenuated for innate and adaptive immune inflammatory permeability responses.
Lam
Bing K
BK
Department of Medicine, Harvard Medical School, Brigham and Women's Hospital, Boston, MA 02115, USA. blam@rics.bwh.harvard.edu
D000818:Animals; D020134:Catalytic Domain; D003545:Cysteine / Q000096:biosynthesis / Q000378:metabolism*; D005978:Glutathione / Q000378:metabolism; D005982:Glutathione Transferase / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007249:Inflammation / Q000201:enzymology; D017572:Leukotriene A4 / Q000378:metabolism; D017997:Leukotriene C4 / Q000096:biosynthesis; D015289:Leukotrienes / Q000096:biosynthesis / Q000378:metabolism*; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology; D008168:Lung / Q000201:enzymology; D008565:Membrane Proteins / Q000378:metabolism; D016297:Mutagenesis, Site-Directed; D012140:Respiratory Tract Diseases / Q000201:enzymology; D014158:Transcription, Genetic
D017572:Leukotriene A4; D015289:Leukotrienes; D016859:Lipoxygenase Inhibitors; D008565:Membrane Proteins; C112381:cysteinyl-leukotriene; D017997:Leukotriene C4; D005982:Glutathione Transferase; C041116:leukotriene-C4 synthase; D005978:Glutathione; D003545:Cysteine