A team led by Klaas Martinus Pos, CEF Investigator and Professor at the Institute of Biochemistry of the Goethe University Frankfurt, used X-ray crystallography to solve high resolution (1.9-2.25 Å) structures of the membrane protein AcrB in complex with multiple antibiotics.
AcrB is the inner-membrane component of the major multidrug efflux transport machinery AcrAB-TolC from Escherichia coli. The study just published in the Proceedings of the National Acadamy of Sciences presents in one of the protein/drug complex structures the drug doxorubicin located in two monomers of trimeric AcrB; a dimeric doxorubicin sandwich bound to a pheripheral acces binding site in one monomer and a single doxorubicin molecule bound to a deeper binding pocket in the other monomer.
The drug binding sites are exclusive for the respective conformational monomers and are separated by a switch-loop, most likely involved in a gating process mediating transport of the drug from the access site to the deep binding site.
