Group:SMART:P-glycoprotein: Why Cancer Drugs Fail
Abraham Lincoln High School, San Francisco CA, SMART TeamAbraham Lincoln High School, San Francisco CA, SMART Team
Team members: Tiffany Cai, Pauline Chan, Maggie Chang, Tina Chen, Desiree Chiu, Jeffrey Chum, Jane Hwang, Nancy Kong, Grace Wang
"Poster Team:" Tiffany Cai, Tina Chen
"Model Team:" Jane Hwang, Nancy Kong, Grace Wang
"Abstract Team:" Pauline Chan, Desiree Chiu
"What is P-gp Team:" Maggie Chang, Jeffrey Chum
Teacher: Mr. Richard Gin
UCSF: Anita Grover (mentor), Ben Koo, Kurt Giles, Sabine Jeske
AbstractAbstract
P-gp is an efflux drug transporter located in the cell membrane of the cell. It transports foreign and unfamiliar substances out of the cell, protecting the body from harmful toxins that stay in the bloodstream. An example would be cleansing toxins from the small intestine when consuming food that may have gone bad. In this case, P-gp would be acting on behalf of our benefit. However, in cancerous cells, P-gp is the main factor that stops treatment from working against cancer. It causes 90% of chemotherapy to fail in patients. Although the drug may be good for the body, P-gp is unable to recognize the drug so it pushes it out of the cell once it enters. P-gp is why most cancer drugs fail to have any effect in the body. Recently the X-ray structure of P-gp was resolved (Aller et al, 2009). We have built a 3-D physical model based on this X-ray structure which highlights the hydrophobic and hydrophilic regions of the protein, nucleotide binding domains, and active site residues that are important for verapamil, a common heart medication, binding. As it has not yet been possible to identify whether a drug is or is not a substrate of P-glycoprotein, this 3-D model may lend insight into this prediction.
Our ModelOur Model
In our model of P-glycoprotein, the hydrophilic regions are highlighted in magenta, the hydrophobic regions are highlighted in violet, the active site residues for the drug Verapamil* is highlighted in green, and the Nucleotide Binding Domains or NBDs are highlighted in yellow. Since P-glycoprotein is a dimer, a molecule consisting of two similar subunits, only half of the dimer (or one of two subunits) is shown in our model.