title: Human leukotriene C(4) synthase at 4.5 A resolution in projection.
abstract: Leukotriene (LT) C(4) synthase, an 18 kDa integral membrane enzyme, conjugates LTA(4) with reduced glutathione to form LTC(4), the parent compound of all cysteinyl leukotrienes that play a crucial role in the pathobiology of bronchial asthma. We have calculated a projection map of recombinant human LTC(4) synthase at a resolution of 4.5 A by electron crystallography, which shows that the enzyme is a trimer. A map truncated at 7.5 A visualizes four transmembrane alpha helices per protein monomer. The densities in projection indicate that most of the alpha helices run nearly perpendicular to the plane of the membrane. At this resolution, LTC(4) synthase is strikingly similar to microsomal glutathione S-transferase 1, which belongs to the same gene family but bears little sequence identity and no resemblance in substrate specificity to the LTC(4) synthase. These results provide new insight into the structure and function of membrane proteins involved in eicosanoid and glutathione metabolism.
authors.affiliation: Department of Structural Biology, Max-Planck-Institute of Biophysics, Marie-Curie-Strasse 15, 60439 Frankfurt am Main, Germany. ingeborg.schmidt-krey@mpibp-frankfurt.mpg.de
authors.forename: Ingeborg
authors.initials: I
authors.lastname: Schmidt-Krey
authors.forename: Yoshihide
authors.initials: Y
authors.lastname: Kanaoka
authors.forename: Deryck J
authors.initials: DJ
authors.lastname: Mills
authors.forename: Daisuke
authors.initials: D
authors.lastname: Irikura
authors.forename: Winfried
authors.initials: W
authors.lastname: Haase
authors.forename: Bing K
authors.initials: BK
authors.lastname: Lam
authors.forename: K Frank
authors.initials: KF
authors.lastname: Austen
authors.forename: Werner
authors.initials: W
authors.lastname: Kühlbrandt
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D017931:DNA Primers; D005982:Glutathione Transferase / Q000737:chemistry*; D006801:Humans; D008854:Microscopy, Electron; D008969:Molecular Sequence Data; D011487:Protein Conformation; D051381:Rats
chemical_list: D017931:DNA Primers; D005982:Glutathione Transferase; C041116:leukotriene-C4 synthase