TY - JOUR
T1 - Microbial drug efflux proteins of the major facilitator superfamily
AU - Saidijam, Massoud
AU - Benedetti, Giulia
AU - Ren, Qinghu
AU - Xu, Zhiqiang
AU - Hoyle, Christopher J.
AU - Palmer, Sarah L.
AU - Ward, Alison
AU - Bettaney, Kim E.
AU - Szakonyi, Gerda
AU - Meuller, Johan
AU - Morrison, Scott
AU - Pos, Martin K.
AU - Butaye, Patrick
AU - Walravens, Karl
AU - Langton, Kate
AU - Herbert, Richard B.
AU - Skurray, Ronald A.
AU - Paulsen, Ian T.
AU - O'Reilly, John
AU - Rutherford, Nicolas G.
AU - Brown, Melissa H.
AU - Bill, Roslyn M.
AU - Henderson, Peter J F
PY - 2006/7
Y1 - 2006/7
N2 - Drug efflux proteins are widespread amongst microorganisms, including pathogens. They can contribute to both natural insensitivity to antibiotics and to emerging antibiotic resistance and so are potential targets for the development of new antibacterial drugs. The design of such drugs would be greatly facilitated by knowledge of the structures of these transport proteins, which are poorly understood, because of the difficulties of obtaining crystals of quality. We describe a structural genomics approach for the amplified expression, purification and characterisation of prokaryotic drug efflux proteins of the 'Major Facilitator Superfamily' (MFS) of transport proteins from Helicobacter pylori, Staphylococcus aureus, Escherichia coli, Enterococcus faecalis, Bacillus subtilis, Brucella melitensis, Campylobacter jejuni, Neisseria meningitides and Streptomyces coelicolor. The H. pylori putative drug resistance protein, HP1092, and the S. aureus QacA proteins are used as detailed examples. This strategy is an important step towards reproducible production of transport proteins for the screening of drug binding and for optimisation of crystallisation conditions to enable subsequent structure determination. © 2006 Bentham Science Publishers Ltd.
AB - Drug efflux proteins are widespread amongst microorganisms, including pathogens. They can contribute to both natural insensitivity to antibiotics and to emerging antibiotic resistance and so are potential targets for the development of new antibacterial drugs. The design of such drugs would be greatly facilitated by knowledge of the structures of these transport proteins, which are poorly understood, because of the difficulties of obtaining crystals of quality. We describe a structural genomics approach for the amplified expression, purification and characterisation of prokaryotic drug efflux proteins of the 'Major Facilitator Superfamily' (MFS) of transport proteins from Helicobacter pylori, Staphylococcus aureus, Escherichia coli, Enterococcus faecalis, Bacillus subtilis, Brucella melitensis, Campylobacter jejuni, Neisseria meningitides and Streptomyces coelicolor. The H. pylori putative drug resistance protein, HP1092, and the S. aureus QacA proteins are used as detailed examples. This strategy is an important step towards reproducible production of transport proteins for the screening of drug binding and for optimisation of crystallisation conditions to enable subsequent structure determination. © 2006 Bentham Science Publishers Ltd.
KW - Antibiotic resistance
KW - Drug resistance
KW - Gene expression
KW - Membrane protein
KW - Membrane transport
KW - Multidrug resistance
KW - Protein production
KW - Transport protein
UR - http://www.scopus.com/inward/record.url?scp=33745741591&partnerID=8YFLogxK
UR - http://www.bentham.org/cdt/contabs/cdt7-7.htm#2
U2 - 10.2174/138945006777709575
DO - 10.2174/138945006777709575
M3 - Article
C2 - 16842212
SN - 1389-4501
VL - 7
SP - 793
EP - 811
JO - Current Drug Targets
JF - Current Drug Targets
IS - 7
ER -