October 24, 2024 | Virtual Event
Ruchika Bajaj
University of California, USA
Ruchika has BSc (H) Biochemistry from University of Delhi and MSc. Biotechnology from Indian Institute of Technology Roorkee, India and received her PhD from Purdue University where she was trained as a Membrane Protein Biologist. Afterwards, she pursued her postdoctoral training at UCSF. She focused on ABC transporters all the way in her scientific training. She is very much passionate in elucidating in mechanistic underpinning of membrane proteins using biochemical, biophysical and structural biology approaches, which could help to rationally design novel pharmacological tools to modulate the function of membrane proteins altered in disease.
Membrane proteins cons4tute 30% of the genome in organisms and are involved in numerous physiological processes. ABC transporters is a class of membrane proteins which are ubiquitously present in all organisms, bind and hydrolyze ATP to power the solute transport and are associated with several human diseases like mul4drug resistance in cancer, macular degenera4on, cys4c fibrosis, re4ni4s pigmentosa etc. ABC transporters consists of two transmembrane domains (TMDs), which form the permea4on pathway and nucleo4de binding domains (NBDs) to bind and hydrolyze ATP and follow alterna4ng access mechanism. Bacterial ABC transporters like binding-protein-independent mutant of maltose transporter, MalG511 from E.coli and FtsEX-PcsB from S. pneumoniae have been characterized biochemically and biophysically to study mechanism and future higher resolu4on studies. Structure-func4on rela4onships were studied in mammalian ABC transporters, bovine MRP4 and human P-glycoprotein. High resolu4on cryoEM structures of bovine MRP4 in three different states (apo state, nucleo4de bound state and substrate bound state) are determined which revealed the architecture, asymmetry of NBDs, interpreted func4onal effects of gene4c variants, located substrate binding site, deciphered associated conforma- 4onal changes in cataly4c cycle of bovineMRP4. Structure based drug designing and targe4ng MRP4 in context of cancer and cardiac diseases will be helpful to the field of medicine. Oral excipients were screened against P-gp using calceinAM fluorescence assay and digoxin flux assay were found to be inert for their effect on P-glycoprotein. beta-Cyclodextrin and light green SF yellowish were found to be inhibitory at high macromolecular range in digoxin flux assay. This informa4on will be helpful in preparing novel generic formula4ons. Addi4onally, the meta-analysis study provides an overview of the revolu4onizing field of structural biology of ABC transporters.
