 |
PDBsum entry 4xwk
|
|
|
|
References listed in PDB file
|
 |
|
Key reference
|
|
|
Title
|
|
Global marine pollutants inhibit p-Glycoprotein: environmental levels, Inhibitory effects, And cocrystal structure.
|
|
|
Authors
|
|
S.C.Nicklisch,
S.D.Rees,
A.P.Mcgrath,
T.Gökirmak,
L.T.Bonito,
L.M.Vermeer,
C.Cregger,
G.Loewen,
S.Sandin,
G.Chang,
A.Hamdoun.
|
|
|
Ref.
|
|
Sci Adv, 2016,
2,
e1600001.
[DOI no: ]
|
|
|
PubMed id
|
|
|
|
|
|
Abstract
|
|
|
The world's oceans are a global reservoir of persistent organic pollutants to
which humans and other animals are exposed. Although it is well known that these
pollutants are potentially hazardous to human and environmental health, their
impacts remain incompletely understood. We examined how persistent organic
pollutants interact with the drug efflux transporter P-glycoprotein (P-gp), an
evolutionarily conserved defense protein that is essential for protection
against environmental toxicants. We identified specific congeners of
organochlorine pesticides, polychlorinated biphenyls, and polybrominated
diphenyl ethers that inhibit mouse and human P-gp, and determined their
environmental levels in yellowfin tuna from the Gulf of Mexico. In addition, we
solved the cocrystal structure of P-gp bound to one of these inhibitory
pollutants, PBDE (polybrominated diphenyl ether)-100, providing the first view
of pollutant binding to a drug transporter. The results demonstrate the
potential for specific binding and inhibition of mammalian P-gp by ubiquitous
congeners of persistent organic pollutants present in fish and other foods, and
argue for further consideration of transporter inhibition in the assessment of
the risk of exposure to these chemicals.
|
|
|
|
|
|
|
