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ATP-binding cassette transporters (ABC transporters) are the largest superfamily of a transport system with representatives in all phyla from prokaryotes to humans.
ABC transporters often consist of multiple subunits, one or two of which are transmembrane proteins (TMDs) and one or two of which are nucleotide binding domains (NBDs) The NBDs utilizes the energy of ATP binding and hydrolysis to energize the translocation of various substrates across membranes, either for uptake or for export of the substrate.
ABC proteins are divided into two classes (i) exporters that mediate the transport of unrelated substances across membranes and (ii) importers which function to allow nutrients into the cell.
My research is currently focusing on these areas:
1. Transport mechanism.
-> How do organisms utilize transporters to shuttle nutrients or toxins across membranes?
2. Classification of ABC transporters.
-> What is the role of regulatory domains in the transport process?
3. Host-pathogen interaction.
-> How do pathogens utilize ABC transporters to circumvent the host innate immune defenses?
Multidrug efflux pumps
Gram-negative bacteria expel a wide range of toxic substances through tripartite drug efflux pumps. These pumps form tripartite assemblies which can span the entire cell envelope, including the inner and outer membranes. Tripartite efflux systems comprise the inner membrane transporter (IMT), an outer membrane protein (OMP), and a periplasmic ‘membrane fusion protein’ (MFP) or adaptor protein. The IMT transports various substrates utilizing a proton gradient (for RND and MFS transporters) or ATP hydrolysis (for ABC transporters), and the OMP provides a continuous conduit through the outer membrane.
In particular, tripartite multidrug efflux pumps located in the membranes rapidly expel a broad range of substances including antibiotics, dyes, detergents, toxic compounds, and organic solvents, conferring a high level of intrinsic antibiotic resistance in many organisms.
Tripartite efflux pumps still have many unknown properties. For example, it remains unknown how the ABC and MFS transporters are assembled in the ternary complex and how the central channel opens subsequently with the complexed substrates. This information will definitely help to develop a new drug and chemotherapy to prevent a multidrug resistance caused by the functional assembly of the complex.
To determine the mechanisms underlying transport and its regulation, I can use a combination of X-ray crystallography, biochemistry, molecular microbiology, and biophysics.
To determine the mechanisms underlying transport and its regulation, I can use a combination of X-ray crystallography, biochemistry, molecular microbiology, and biophysics.
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