Overview
My group is interested in the structure elucidation of membrane proteins involved in drug transport. In addition, we are looking to understand how the bacterial cells can sense and respond to antibiotics at the DNA level. We are also interested to understand how bacteria detoxify heavy metals by using enzymes and membrane proteins.
AcrB multidrug resistance pump
AcrB is a very well studied multidrug resistance pump from gram negative bacteria. Gastrointestinal bacteria such as E. coli must remove bile acid to
survive in the gut; the bile acid can act as a detergent and disrupt the bacterial membrane and lead to the cell death. We have solved the structure of AcrB in the presence of deoxycholate at 3.85 Å resolution. AcrB has evolved to continuously pump the deoxycholate out of the cell and the structure provides us with useful mechanistic information on this process.
BaeR response regulator
Bacteria are able to sense, respond and regulate expression of genes that code for various membrane bound multidrug resistant pumps and transporters; thei expression is regulated on the transcription level. Response regulators are
phosphorylated by a histidine kinase, dimerise and bind to DNA. We have
solvedthe structure of the dimeric form of the unphosphorylated response regulator BaeR from E. coli at 3.3 Å resolution. The structure provides us with a possible model on how some unphosphorylated response regulators can bind DNA.
TehB Chalcogen detoxification
Bacteria can detoxify heavy metals by reducing them to their elemental state or by methylating them. The methylated species can either be volatile or can be extruded by dedicated membrane proteins. Tellurium and selenium are heavy metals found as trace elements in soil or as
contaminants of industrial processes. Tellurite and selenium can be methylated b
y TehB and extruded out of the cell by TehA. We have solved the structure of TehB at 1.5 Å resolution in the presence of the cofactor analogue SAH. Our biochemical data show that the protein does not discriminate between Tellurium or Selenium for methylation, but cannot methylate arsenic species.