TY - JOUR
T1 - Assembly and transport mechanism of tripartite drug efflux systems
AU - Misra, Rajeev
AU - Bavro, Vassiliy N.
N1 - Funding Information:
We would like to thank Jon Weeks for reading the manuscript and assistance in making Figs. 1 and 3 . This work was supported in part by a grant R01 GM66988 from the National Institutes of Health to RM.
PY - 2009/5
Y1 - 2009/5
N2 - Multidrug efflux (MDR) pumps remove a variety of compounds from the cell into the external environment. There are five different classes of MDR pumps in bacteria, and quite often a single bacterial species expresses multiple classes of pumps. Although under normal circumstances MDR pumps confer low-level intrinsic resistance to drugs, the presence of drugs and mutations in regulatory genes lead to high level expression of MDR pumps that can pose problems with therapeutic treatments. This review focuses on the resistance nodulation cell division (RND)-class of MDR pumps that assemble from three proteins. Significant recent advancement in structural aspects of the three pump components has shed new light on the mechanism by which the tripartite efflux pumps extrude drugs. This new information will be critical in developing inhibitors against MDR pumps to improve the potency of prescribed drugs.
AB - Multidrug efflux (MDR) pumps remove a variety of compounds from the cell into the external environment. There are five different classes of MDR pumps in bacteria, and quite often a single bacterial species expresses multiple classes of pumps. Although under normal circumstances MDR pumps confer low-level intrinsic resistance to drugs, the presence of drugs and mutations in regulatory genes lead to high level expression of MDR pumps that can pose problems with therapeutic treatments. This review focuses on the resistance nodulation cell division (RND)-class of MDR pumps that assemble from three proteins. Significant recent advancement in structural aspects of the three pump components has shed new light on the mechanism by which the tripartite efflux pumps extrude drugs. This new information will be critical in developing inhibitors against MDR pumps to improve the potency of prescribed drugs.
KW - Drug resistance
KW - Membrane fusion protein
KW - Outer membrane protein factor
KW - Proton/drug antiporter
KW - RND-type multidrug efflux pump
KW - Tripartite pump assembly
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U2 - 10.1016/j.bbapap.2009.02.017
DO - 10.1016/j.bbapap.2009.02.017
M3 - Review article
C2 - 19289182
AN - SCOPUS:64649089196
SN - 1570-9639
VL - 1794
SP - 817
EP - 825
JO - Biochimica et Biophysica Acta - Proteins and Proteomics
JF - Biochimica et Biophysica Acta - Proteins and Proteomics
IS - 5
ER -