Ramaswamy
Krishnamoorthi
Associate Professor of Biochemistry
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).
B.Sc. 1973,
University of Madras
M.Sc. 1975, University of Madras
Ph.D. 1983, University of California, Davis
Phone: 785-532-6262
Fax: 785-532-7278
Email: krish@ksu.edu
Office: 63 Chalmers
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
Shan, J., M. Baguinon, L. Zheng, and R. Krishnamoorthi. Expression, refolding, and activation of the catalytic domain of human blood coagulation factor XII, Protein Express. Purif. 27, 143-149 (2003).
Cai, M., Y. Gong, L. Wen, and R. Krishnamoorthi. 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 (2002).
M. Zavodszky, C.-W. Chen, J.-K. Huang, M. Zolkiewski, L. Wen, and R.
Krishnamoorthi. Disulfide bond effects on protein stability: Designed variants
of Cucurbita maxima trypsin inhibitor-V. Protein Sci. 10 , 149-160 (2001).
L. Zheng, R. Krishnamoorthi, M. Zolkiewski, and X. Wang. Distinct Ca2+-binding properties of novel C2 domains of plant phospholipase Da and b. J. Biol. Chem. 275 , 19700-19706 (2000).