June 17, 2005  
 

 

Light Sources Study Protein Involved in Drug Resistance

By Heather Rock Woods

Overall structure of MsbA in complex with ADP, vanadate, Mg2+ and Ra lipopolysaccharide (LPS).
(Image courtesy of Geoffrey Chang & Christopher Reyes)

Scientists at The Scripps Research Institute have solved the structure of a protein called MsbA which is used by bacteria and cancer cells to resist therapeutic drugs. Researchers Geoffrey Chang and Christopher Reyes solved the structure using high-resolution x-ray crystallography at SSRL and at the Advanced Light Source in Berkeley.

The proteinís shape is described in the May 13 issue of the journal Science. MsbA is a protein that sits in cell membranes and transports items between the outside and the inside of cells. Bacteria use MsbA transporters to quash antibiotics; human cancer cells have similar membrane transporters on their surfaces that undermine the potency of chemotherapy drugs. The research has revealed molecular details that could be useful for improving cancer therapy and fighting antibiotic-resistant bacteria that have become an increasingly dangerous problem in recent years.

MsbA molecules play an essential role for bacteria because they help build bacterial cell walls by flipping molecules from the inner membrane to the outer membrane. This is likely what happens when transporters neutralize antibiotics by pumping them out of cells. Knowing the structure of MsbA may help scientists to design compounds to block the transporterís action.

People have transporter proteins similar to MsbA that play an essential protective role by removing harmful toxins. This protective role can reduce the efficacy of certain cancer treatments because the drugs are perceived as toxins. Understanding the high-resolution structure could open the door for scientists to design a new class of drugs to keep antibiotic or chemotherapeutic agents inside target cells, thus increasing the drugsí efficacy.

 

The Stanford Linear Accelerator Center is managed by Stanford University for the US Department of Energy

Last update Wednesday June 15, 2005 by Topher White