3pcv
From Proteopedia
Crystal structure analysis of human leukotriene C4 synthase at 1.9 angstrom resolution
Structural highlights
DiseaseLTC4S_HUMAN Defects in LTC4S are the cause of leukotriene C4 synthase deficiency (LTC4 synthase deficiency) [MIM:246530. LTC4 synthase deficiency is a fatal neurometabolic developmental disorder. It is associated with muscular hypotonia, psychomotor retardation, failure to thrive, and microcephaly. FunctionLTC4S_HUMAN Catalyzes the conjugation of leukotriene A4 with reduced glutathione to form leukotriene C4. Publication Abstract from PubMedLeukotriene (LT) C(4) and its metabolites, LTD(4) and LTE(4), are involved in the pathobiology of bronchial asthma. LTC(4) synthase is the nuclear membrane-embedded enzyme responsible for LTC(4) biosynthesis, catalyzing the conjugation of two substrates that have considerably different water solubility; that amphipathic LTA(4) as a derivative of arachidonic acid and a water-soluble glutathione (GSH). A previous crystal structure revealed important details of GSH binding and implied a GSH activating function for Arg-104. In addition, Arg-31 was also proposed to participate in the catalysis based on the putative LTA(4) binding model. In this study enzymatic assay with mutant enzymes demonstrates that Arg-104 is required for the binding and activation of GSH and that Arg-31 is needed for catalysis probably by activating the epoxide group of LTA(4). The catalytic architecture of leukotriene C4 synthase with two arginine residues.,Saino H, Ukita Y, Ago H, Irikura D, Nisawa A, Ueno G, Yamamoto M, Kanaoka Y, Lam BK, Austen KF, Miyano M J Biol Chem. 2011 May 6;286(18):16392-401. Epub 2011 Mar 16. PMID:21454538[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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