Download Slide ()

General structure of ABC membrane drug efflux pumps. A) (left) Shown is a linear topological cartoon of the core structure of ABC transporters such as Pglycoprotein showing the 2 cytoplasmic nucleotide-binding domains (NBDs) and 12 transmembrane (TM) helices (here shown as cylinders) equally
distributed between 2 membrane-spanning domains (MSDs). (right) Shown is a 3D homology model of the core structure of MRP1 (lacking MSD0, see Fig
19–5B) generated using the crystal structure of Staphylococcus aureus Sav1866 as template (Hollenstein et al, 2007; DeGorter et al, 2008). The α-carbon
backbone in ribbon representation of the core structure (MSD1-NBD1-MSD2-NBD2) is viewed from the plane perpendicular to the membrane bilayer
(DeGorter et al, 2008). Homology models of P-glycoprotein, MRP4 and other ABC transporters look very similar. The 2 NBDs form a "sandwich" dimer for
Source: Drug Resistance, The Basic Science of Oncology, 5e
the effective binding and hydrolysis of 2 molecules of ATP, providing the energy for the transport process. Signaling between the MSDs (translocation
Citation:
IF, Hill
RG, Harrington
L. The
Basicfor
Science
of Oncology,
5e; by
2016
Available
at: http://mhmedical.com/
pathway through
the Tannock
membrane)
andRP,
theBristow
NBDs (which
provide the
energy
transport)
is mediated
specific
sequences
in the cytoplasmic loops.
Accessed:
May
10,
2017
Substrates that enter the cell by diffusion or active transport, or are formed in the cell by conjugation, are thought to be exported from the cell either directly
Copyright
McGraw-Hill
rights reserved
through the pore
from ©
the2017
cytoplasm,
or in Education.
the case ofAll
hydrophobic
drugs, are taken up from the inner leaflet of the membrane lipid bilayer. B) Domain
organization of ABC transporter drug (and drug metabolite) efflux pumps implicated in drug resistance in malignant cells. P-glycoprotein and the MRPs are