Membrane Protein Biology


Research Interests

Structural Biology of Membrane Protein Systems; Chloride Intracellular Channels, plasmid fertility inhibition; structure based drug discovery for novel therapeutics for atherosclerosis, cancer and sepsis; deciphering the molecular basis of Indian traditional medicine used for cardio and cerebrovascular therapy work. Foldscope for teaching and research.

Description of Research

We aim to understand membrane protein systems that mediate complex biological processes and translate these for future therapies by using biochemistry, biophysics, enzymology, X-ray crystallography, structure-based drug discovery, cell-based assays tools and through institutional collaborations.

1) Vitamin-C recycling in human health and crop improvement: we aim to understand the structural basis of Vitamin-C recycling by dimorphic bifunctional dehydroascorbate (DHA) reductases (DHARs) that also act as ion channels. Highly conserved across species, these exist as soluble enzymes and as ion-channels when membrane is inserted. Human Chloride Intracellular Channels (CLICs) come under this class of proteins which are overexpressed in many cancers. In addition to targeting high-resolution ionchannel structure, we explore both forms of HsCLICs as novel anti-cancer targets for discovery of small molecular inhibitors and plant DHARs (CLICs) for crop improvement. We also work on Monodehydro ascorbate (MDHA) reductase (MDHAR) enzyme that recycles Vitamin-C from MDHA in plants.

Structure based inhibitor discovery for Atherosclerosis: Ox-LDL plays a vital role in the development of atherosclerosis and other cardio and cerebrovascular diseases. Lectin-like oxidized low-density lipoprotein receptor1 (LOX-1) is a scavenger receptor predominantly expressed on the vascular endothelial cell surface and aids in binding and internalisation of oxidized low-density lipoproteins (Ox-LDL), resulting in plaque formation in the arteries and further pathology of atherosclerosis. We screen, design and validate small molecules that target Ox-LDL binding to LOX-1 for novel therapeutics to treat cardio cerebrovascular diseases, and have recently initiated a new programme to decipher the molecular mechanism of action of Indian traditional medicines used in cardiovascular therapy, using modern biological tools.

Plasmid fertility inhibition (FIN) systems: We try to understand the molecular mechanisms of diverse strategies used by competing conjugative self-transmissible plasmids to block the translocation of rival DNA at the respective type IV secretion system (T4SS). Our long-term goal is to develop therapeutics targeting T4SS to intervene in the emergence of antibiotic resistance in bacteria through horizontal gene transfer.

Novel antibiotic discovery for sepsis: Sepsis mediating bacterial pathogens are especially rampant in neonates and immunocompromised adults. With the emergence of MDR and XDR types, treatment in clinics and hospitals has become challenging, leading to increased morbidity and mortality. Targeting septicaemia with empirical broad-spectrum antibiotics has only led to selection of resistant mutants within the infecting pathogen pool. To reduce the emergence of antimicrobial resistance, targeting essential virulence proteins is an upcoming strategy. We are exploring outer membrane phospholipase A (OMPLA) of Acinetobacter baumannii and Klebsiella pneumoniae for novel antibiotics discovery.

Foldscope for tracking crystallization and imaging: As part of the Department of Biotechnology, Government of India outreach programme, we are taking Foldscopes to schools and colleges in the country for teaching crystallization and imaging.

Dimorphic and bi-functional CLICs are overexpressed in various cancers and are highly conserved across species.


Khan MA, Mohammad I, Banerjee S, Tomar A, Varughese KI, Mehta JL, Chandele A, Arockiasamy A. Oxidized LDL receptors: a recent update. Curr OpinLipidol. 2023 May 5. doi: 10.1097/MOL.0000000000000884. Epub ahead of print. PMID: 37171285.

Das BK, Khan WA, Sreekumar SN, Ponraj K, Achary VMM, Reddy ES, Balasubramaniam D, Chandele A, Reddy MK, Arockiasamy A. Plant dehydroascorbate reductase moonlights as membrane integrated ion channel. Arch Biochem Biophys. 2023 Jun;741:109603. doi: 10.1016/ Epub 2023 Apr 19. PMID: 37084805.

Fatima U, Balasubramaniam D, Khan WA, Kandpal M, Vadassery J, Arockiasamy A, Senthil-Kumar M. AtSWEET11 and AtSWEET12 transporters function in tandem to modulate sugar flux in plants. Plant Direct. 2023 Mar 8;7(3):e481. doi: 10.1002/pld3.481. PMID: 36911252; PMCID: PMC9995347.

Tomar A, Sahoo S, Aathi M, Kuila S, Khan MA, Ravi GRR, Jeyaraman J, Mehta JL, Varughese KI, Arockiasamy A. Exploring the druggability of oxidized low-density lipoprotein (ox-LDL) receptor, LOX-1, a proatherogenic drug target involved in atherosclerosis. Biochem Biophys Res Commun. 2022 Oct 1;623:59-65. doi: 10.1016/j.bbrc.2022.07.036. Epub 2022 Jul 12. PMID: 35872543.
Fatima, U., Balasubramaniam, D., Khan, W. A., Kandpal, M., Vadassery, J., Arockiasamy, A., & Senthil-Kumar, M. (2023). AtSWEET11 and AtSWEET12 transporters function in tandem to modulate sugar flux in plants. Plant Direct, 7( 3), e481.