Leukotriene C4 synthase: a critical enzyme for the biosynthesis of SRS-A.
Leukotriene (LT) C4 synthase catalyzes the conjugation of LTA4 with reduced glutathione (GSH) to form LTC4, the parent compound of cysteinyl leukotrienes. It is a 18 kDa protein that functions as homodimer. Cloning of LTC4 synthase cDNA reveals amino acid homology with 5-lipoxygenase activating protein (FLAP) and newly identified microsomal glutathione S-transferase II (mGST-II) but not with cytosolic GSTs or mGST-I. LTC4 synthase gene contains 5 exons and four introns. This gene has been localized to the long arm of human chromosome 5 at the region of 5q35 which is in close proximity to the cluster of genes that are involved in inflammation and asthma. Mutagenic studies reveals that amino acid residues Arg-51 and Tyr-93 are critical for catalytic function. Arg-51 was proposed to open the epoxide ring of LTA4 and Tyr-93 to provide the thiolate anion of GSH.
Lam
B K
BK
Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, and Department of Medicine, Harvard Medical School, Boston, MA 02115, USA. bingklam@ mbcrr.harvard.edu
D002384:Catalysis; D002874:Chromosome Mapping; D018076:DNA, Complementary; D005982:Glutathione Transferase / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D011994:Recombinant Proteins; D013189:SRS-A / Q000096:biosynthesis*
D018076:DNA, Complementary; D011994:Recombinant Proteins; D013189:SRS-A; D005982:Glutathione Transferase; C041116:leukotriene-C4 synthase