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Light Sources Study Protein Involved in Drug Resistance
By Heather Rock Woods
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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
protein’s 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
transporter’s 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 drugs’ efficacy. |
