The structure of membrane associated proteins in eicosanoid and glutathione metabolism as determined by electron crystallography.
Membrane associated proteins in eicosanoid and glutathione metabolism (MAPEG) are involved in biosynthesis of arachidonic-derived mediators of pain, fever, and inflammation as well as in biotransformation and detoxification of electrophilic substances. Structure determination of microsomal glutathione transferase 1 using electron crystallography has provided the first atomic model of an MAPEG member. The homotrimer consists of three repeats of a four-helix transmembrane bundle with the largest extramembranous domain connecting the first and second helix and with a short proline rich loop on the same side between helices three and four. Residues of importance for intramolecular or intermolecular contacts as well as for stabilizing the active site have been identified and the results can be applied for interpreting structure-function relationship for similar MAPEG members.
Hebert
Hans
H
Karolinska Institutet, Department of Biosciences and Nutrition and Royal Institute of Technology, School of Technology and Health, Novum, S-141 57 Huddinge, Sweden. Hans.Hebert@csb.ki.se
Jegerschöld
Caroline
C
D000595:Amino Acid Sequence; D001665:Binding Sites; D018360:Crystallography, X-Ray; D015777:Eicosanoids / Q000378:metabolism*; D005978:Glutathione / Q000378:metabolism*; D005982:Glutathione Transferase / Q000737:chemistry; D008565:Membrane Proteins / Q000737:chemistry* / Q000378:metabolism; D008854:Microscopy, Electron; D008954:Models, Biological; D008958:Models, Molecular; D008969:Molecular Sequence Data
D015777:Eicosanoids; D008565:Membrane Proteins; C122107:microsomal glutathione S-transferase-I; D005982:Glutathione Transferase; D005978:Glutathione