Structure and function of a squalene cyclase.
The crystal structure of squalene-hopene cyclase from Alicyclobacillus acidocaldarius was determined at 2.9 angstrom resolution. The mechanism and sequence of this cyclase are closely related to those of 2,3-oxidosqualene cyclases that catalyze the cyclization step in cholesterol biosynthesis. The structure reveals a membrane protein with membrane-binding characteristics similar to those of prostaglandin-H2 synthase, the only other reported protein of this type. The active site of the enzyme is located in a large central cavity that is of suitable size to bind squalene in its required conformation and that is lined by aromatic residues. The structure supports a mechanism in which the acid starting the reaction by protonating a carbon-carbon double bond is an aspartate that is coupled to a histidine. Numerous surface alpha helices are connected by characteristic QW-motifs (Q is glutamine and W is tryptophan) that tighten the protein structure, possibly for absorbing the reaction energy without structural damage.
Wendt
K U
KU
Institut für Organische Chemie und Biochemie, Albertstrasse 21, D-79104 Freiburg im Breisgau, Germany.
Poralla
K
K
Schulz
G E
GE
D000595:Amino Acid Sequence; D001406:Bacillaceae / Q000201:enzymology*; D001665:Binding Sites; D002462:Cell Membrane / Q000201:enzymology; D003460:Crystallization; D018360:Crystallography, X-Ray; D003500:Cyclization; D019281:Dimerization; D006801:Humans; D006860:Hydrogen Bonding; D019751:Intramolecular Transferases; D007535:Isomerases / Q000737:chemistry* / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011487:Protein Conformation; D017510:Protein Folding; D017433:Protein Structure, Secondary; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D016415:Sequence Alignment; D013185:Squalene / Q000378:metabolism; D013816:Thermodynamics
D011994:Recombinant Proteins; D013185:Squalene; D007535:Isomerases; D019751:Intramolecular Transferases; C066630:squalene-hopene cyclase; C021924:lanosterol synthase