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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.
.
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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