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Kottayil I. Varughese
Professor
Ph.D., University of Madras, India
Office: (501) 686-7160
Lab: (501) 686-7159
Email:
KIVarughese@uams.ed

We are interested in the analysis of structure and function of biological macromolecules using crystallographic techniques. Our research comprises three main areas: (i) Bacterial signaling (ii) Interactions of von Willebrand Factor and thrombin with platelet receptors (iii) Interactions of methamphetamine and other drugs of abuse with therapeutic antibodies.  

(i)  One of the major regulatory mechanisms in bacteria is the two-component system. A typical bacterium possesses dozens of two-component systems regulating various pathways. In these systems, the transmission of signals is accomplished through the exchange of phosphoryl groups from one protein to another. We are studying the mode of recognition and communication between components of these signaling pathways.

(ii) Thrombin plays many diverse roles in various aspects of blood coagulation. It interacts with platelets through certain receptors, like glycoprotein Iba (GP Iba). Currently, we are studying the interactions of a-thrombin with GP Iba at the atomic level with particular emphasis on the role of sulfation of three tyrosine residues of receptor GP Iba.

(iii) In order to find a solution to serious heath problems arising from methamphetamine (METH) abuse, the Owens laboratory at UAMS has developed efficient monoclonal antibodies to be used as therapeutic agents against METH. In order to design antibodies with even higher binding affinities, we are studying the interactions between these antibodies and METH at the atomic level.

Our laboratory has been recognized as a UAMS COM core facility for crystallography.

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 Representative Publications

Zhao H., Violov A., Veldore V. H., Hoch J. A. and Varughese K. I. Crystal structure of the transcriptional repressor PagR of Bacillus anthracis.  Microbiology 156: 385-391, 2010

Celikel R., Peterson EC, Owens S.M., Varughese K.I. Crystal structures of a therapeutic single chain antibody in complex with two drugs of abuse-Methamphetamine and 3,4-methylenedioxymethamphetamine. Protein Science 18 : 2336-45, 2009

Varughese K.I., Zhao H., Veldore, V. H. and Zapf J. Sporulation phosphorelay proteins and their complexes: Crystallographic characterization. Methods in Enzymology: 2007 Volume 422: 102-122

Celikel, R., McClintock, R. A., Roberts, J. R, Mendolicchio, G. L., Ware, J., Varughese, K. I., and Ruggeri. Z. M.,  Modulation of α-thrombin function by distinct interactions with platelet glycoprotein Ibα. Science 2003 301: 218-221.

Celikel, R., Ruggeri, Z.M., and Varughese, K.I.  Modulation of von Willebrand factor conformation and adhesive function by an internalized water molecule.  Nature Structural Biology 2000 7: 881-884.

Link to Dr. KI Varughese at PubMed

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