Conversion of squalene to the pentacarbocyclic hopene.
The membrane protein squalene-hopene cyclase was cocrystallized with 2-azasqualene and analyzed by X-ray diffraction to 2.13 A resolution. The conformation of this close analog was clearly established, and it agreed with the common textbook presentation. The bound squalene undergoes only small conformational changes during the formation of rings A through D, thus requiring no intermediate. However, ring E formation is hindered by an entropic barrier, which may explain its absence in the steroids. The structure analysis revealed a mobile region between the active center cavity and the membrane, which may melt, opening a passage for squalene and hopene.
Reinert
Dirk J
DJ
Institut für Organische Chemie und Biochemie, Albert-Ludwigs-Universität, Albertstr. 21, D-79104 Freiburg, Germany.
Balliano
Gianni
G
Schulz
Georg E
GE
D001406:Bacillaceae / Q000201:enzymology; D001665:Binding Sites; D002384:Catalysis; D002462:Cell Membrane / Q000378:metabolism; D018360:Crystallography, X-Ray; D003500:Cyclization; D019751:Intramolecular Transferases / Q000032:analysis / Q000737:chemistry* / Q000378:metabolism; D008565:Membrane Proteins / Q000032:analysis / Q000737:chemistry* / Q000378:metabolism; D008958:Models, Molecular; D011487:Protein Conformation; D013185:Squalene / Q000031:analogs & derivatives / Q000737:chemistry*; D014315:Triterpenes / Q000138:chemical synthesis*
C491033:2-azasqualene; D008565:Membrane Proteins; D014315:Triterpenes; C028765:diploptene; D013185:Squalene; D019751:Intramolecular Transferases; C066630:squalene-hopene cyclase