Present Position and Address

5.140A Medical Research Bldg.
Mail Route:1055
Telephone: (409) 772-2238
Fax: (409) 772-1790
Email: krrajara@utmb.edu

B.S. 1981 Loyola College, India
M.S. 1983 Indian Institute of Technology, India
M.S. 1987 Michigan State University
Ph.D. 1991 University of California at Davis

RESEARCH INTERESTS:

A schematic of the solution structure of a monomeric interleukin-8 highlighting the different secondary structural features.

Our laboratory is interested in exploiting the structural elements of proteins for rational drug design. Chemokines, a large family of cytokines, have gained tremendous attention in recent years for their role in immune and inflammation related processes, HIV infection, metastasis, and organogenesis. They mediate their function by binding to G-protein coupled 7-TM receptors on leukocytes. We are interested in understanding the molecular basis of ligand-receptor interaction. Knowledge of the structure, dynamics, and thermodynamics of the ligand in the free and the receptor-bound form is essential to accomplish this goal. It is now possible to determine structures of proteins and protein-receptor complexes beyond 20 to 30 kDa due to advances in NMR methodology and availability of high field spectrometers. We will use a variety of multinuclear and multidimensional NMR techniques in conjunction with protein engineering and molecular modeling. These studies will form the foundation for designing lead compounds that could function as drugs for diseases such as cancer, heart diseases, and AIDS.

RECENT PUBLICATIONS:

1. Rajarathnam, K., Li, Y., Rohrer, T., and Gentz, R. Solution Structure and Dynamics of Myeloid Progenitor Inhibitor Factor-1 (MPIF-1): A Novel Monomeric CC Chemokine. J. Biol. Chem. 276:4909-4916 (2001).
2. Sharma, D., and Rajarathnam, K. Relationship Between 13C NMR Chemical Shifts and Disulfide Bond Formation. J. Biomol NMR 18:165-171 (2000).
3. Rajarathnam, K., Dewald, B., Baggiolini, M., Sykes, B. D., and Clark-Lewis, I. Disulfide Bridges in Interleukin-8 Probed Using Non-Natural Disulfide Analogs: Dissociation of Roles in Structure and Function. Biochemistry 38:7653-7658 (1999).
4. Crump, M., Rajarathnam, K., Kim, K-S., Clark-Lewis, I., and Sykes, B. D. Solution Structure of Eotaxin: a Chemokine that Selectively Recruits Eosinophils in Allergic Inflammation. J. Biol. Chem. 273:22471-22479 (1998)
5. Rajarathnam, K., Sykes, B. D., Kay, C. M., Dewald, B., Baggiolini, M., and Clark-Lewis, I. Neutrophil Activation by a Monomeric Interleukin-8. Science 264: 90-92 (1994).