Year: 2011
Type: article
Abstract: Leukotriene (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).
Source: Journal of Biological Chemistry
Institutions: SPring-8, RIKEN, Brigham and Women's Hospital, Harvard University
Language: English
Subfield: Biochemistry
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $3,430
Awards: Cellular Basis of Hypersensitivity Diseases in Humans, CELLULAR BASIS OF HYPERSENSITIVITY DISEASES, Structure and function of the membrane protein human leukotriene C4 synthase, Immune Regulation of Cysteinyl Leukotriene Biosynthesis, REENTRANT WAVE FRONTS IN ATRIAL FIBRILLATION, Chemical Mediators of Acute Pulmonary Disorders, G7474807261, G768979540
OpenAlex ID: W1974813697