Virtuelle (Nano) Welten PDB Molecule of the Month 96: Oxidosqualene Cyclase

Exploring the Structure

You can see both the beginning and the end of the cyclization reaction in two structures, but you need to look at slightly different enzymes. PDB entry 1ump, shown here on the left, is the bacterial enzyme squalene cyclase with a modified form of squalene bound in the active site. Notice how the enzyme forces the snaky molecule into a zig-zag shape. This arranges the chain perfectly, allowing an aspartate amino acid activated by a histidine (both at the top) to start a cascade of reactions that form the four linked rings. PDB entry 1w6k, shown on the right, has the final product lanosterol bound to the human enzyme oxidosqualene cyclase. It also uses an aspartate amino acid to catalyze the reaction, but it is activated by two cysteines instead of a histidine.

These pictures were created with RasMol. To create similar pictures, you can click on the accession codes here and pick one of the options under Images and Visualization. To see the scientific papers used to research this Molecule of the Month, click here. Also available are related entries in the PDB as determined by a keyword search on November 27, 2007 for 'oxidosqualene cyclase'.