Ramaswamy Krishnamoorthi, Ph.D., Associate Professor Emeritus

Image of Ramaswamy Krishnamoorthi

Contact information

E-mail: krish@ksu.edu

Education

B.S. 1973, University of Madras
M.S. 1975, University of Madras
Ph.D. 1983, University of California, Davis

Areas of specialty

  • Structural biology
  • NMR studies of protein structure, dynamics and stability in relation to function
  • Serine proteinases and their protein inhibitors
  • Protein domains involved in signal transduction (plant phospholipase D domains; insect glucan-binding proteins)

To better understand the role and structural modulation of internal dynamics in protein function and to elucidate structure-function correlations, we are characterizing solution structures, internal dynamics, and stabilities of pumpkin seed (Cucurbita maxima) trypsin inhibitors (CMTI) as model systems. We are also investigating the structural and mechanistic details of activation of blood coagulation factor XII (FXII), a serine protease zymogen. Activated FXII (FXIIa) initiates the intrinsic pathway of blood coagulation. High levels of activated FXIIa are associated with coronary heart disease, sepsis, and diabetes. We have developed a recombinant system of FXII that is activated by a single peptide-bond hydrolysis. Using CMTI-V and designed variants with substitutions in the binding-lloop region as a probes, we intend to identify specific residues influencing FXII activation and function and to determine the basis for FXII substrate specificity.

In collaboration with Professor Xuemin Wang (University of Missouri at St. Louis), we are obtaining structural and dynamic descriptions of Ca(II) and phosphatidylinositol 4,5-bisphosphate binding domains of plant phospholipase D isozymes which are involved in signal transduction and stress responses. Results from our studies will help understand the details of protein-lipid and protein-ligand interactions.

In a third area of research, in collaboration with Professor Michael Kanost, we are characterizing structural and dynamic properties of ligand-free and ligand-bound b-1,3-glucan binding protein from the insect, Indian mealmoth. Delineation of protein-carbohydrate interactions, which initiate the insect’s innate immune response to bacterial and fungal attacks, may assist in developing strategies for controlling diseases and economic damages caused by insects.

In addition to NMR spectroscopy, we use CD and microcalorimetry in our investigations.

Selected publications

Takahashi, D., Dai, H., Hiromasa, Y., Krishnamoorthi, R., & Kanost, M.R. (2014) Self-association of an Insect b-1,3-Glucan Recognition Protein Upon Binding Laminarin Stimulates Prophenoloxidase Activation as Innate Immune Response. J. Biol. Chem. 289, 28399-28410.

Dai, H., Hiromasa, Y., Takahashi, D., VanderVelde, D., Fabrick, J., Kanost, M.R., & Krishnamoorthi, R. (2013) An Initial Event in the Insect Innate Immune Response: Structural and Biological Studies of Interactions between β ‑ 1,3-Glucan and the N ‑ Terminal Domain of β ‑ 1,3-Glucan Recognition Protein, Biochemistry 52, 161-170.

Pappan, K., Zheng, L., Krishnamoorthi, R., and Wang, X. (2004) Evidence for and characterization of Ca2+ binding to the catalytic region of Arabidopsis thaliana phospholipase D beta. Journal of Biological Chemistry 279:47833-47839.

Shan, J., Baguinon, M., Zheng, L., and Krishnamoorthi, R. (2003) Expression, refolding, and activation of the catalytic domain of human blood coagulation factor XII, Protein Express. Purif. 27, 143-149.

Cai, M., Gong, Y., Wen, L., and Krishnamoorthi, R. (2002) Correlation of binding-loop internal dynamics with stability and function in potato I inhibitor family: relative contributions of Arg50 and Arg52 in Cucurbita maxima trypsin inhibitor-V as studied by site-directed mutagenesis and NMR spectroscopy. Biochemistry 41, 9572-9579.

Zavodszky, M., Chen, C.-W., Huang, J.-K., Zolkiewski, M., Wen, L., and Krishnamoorthi, R. (2001) Disulfide bond effects on protein stability: Designed variants of Cucurbita maxima trypsin inhibitor-V. Protein Sci. 10:149-160.

Zheng, L., Krishnamoorthi, R., Zolkiewski, M., and Wang, X. (2000) Distinct Ca2+-binding properties of novel C2 domains of plant phospholipase Da and b. J. Biol. Chem. 275:19700-19706.

Complete Publications List