One of the CBI Molecules being studied in the University of Massachusetts Amherst Chemistry-Biology Interface Program at UMass Amherst and on display at the Molecular Playground.
Human beta-glucocerebrosidase, also known as glucoceremidase, GCase, and velaglucerase, is an enzyme that is commonly found to be deficient in patients with Gaucher's disease. Currently, there are three drugs on the market to treat this disease. One being Genzyme's Cerezyme, Protalix's Taliglucerase and SHIRE's VPRIV.
The typical method used to sequence current biologics, as well as map post translational modifications, is a combination of proteolytic digestion followed by LC/MS. Unfortunately, sometimes this method is not enough for complete identification of some post translational modifications. I am interested in the oxidation of Cys residues for the formation of disulfide bonds.
Human beta-glucocerebrosidase (GCase) has seven Cys residues, four of which make two disulfide bonds. These two disufide bonds are both located in the N-terminal region of the protein and separated by only one amino acid. One of my current projects is using mass spectrometry to discern the disulfide connectivity in regions of a protein that are rich with Cys residues.
GCase N-terminal residues 1-23: ARPCIPKSFGYSSVVCVCNATYCDS
Disulfide Connectivity: C4-C16 & C18-C23
3D structures of velaglucerase
For additional information, see: Metabolic Disorders