Research Areas:
Protein chemistry, Structure-function
relationships, Protein-protein interaction and Protein design and
engineering.
Research Interests
The overall objective is to understand
structure-function relationships of proteins, particularly snake
venom toxins, and their mechanism. Snake venoms are rich sources
of toxins that interfere with various physiological processes. We
are specifically interested in protein families of phospholipase
A2 (PLA2) enzymes, serine proteinases, three-finger toxins and helveprins.
The functional diversity despite the structural similarity and the
presence of functional sites in different segments of the toxins
makes our research interesting and challenging. The functional sites
are used in designing proteins with novel biological activities
and prototypes of therapeutic agents.
Current projects:
Snake venom proteins that affect thrombosis and hemostasis
 Several toxins interfere in blood coagulation
and platelet aggregation. We study the structure-function relationships
and mechanism of anticoagulant and antiplatelet proteins, particularly
PLA2 enzymes. The strongly anticoagulant PLA2 binds to factor Xa
and specifically inhibits the prothrombinase complex. Based on the
anticoagulant site of PLA2, we are attempting to identify the functional
sites of coagulation factors. We also determine the structure of
venom prothrombin activators that are structural and functional
homologs of coagulation factors. Based on their structures, we are
designing anticoagulant peptides. Design
and development of bioactive peptides
We have identified anticoagulant, antiplatelet
and hypotensive sites in snake venom toxins. We are currently designing
more potent and stable short peptides. We also plan to develop proteins
with novel functions using these functional sites. We also design
of short peptides with specific structural folds.
Purification and characterization of novel toxins
We isolate and characterize novel toxins
that are found in the venoms in small quantities. We have isolated
and characterized several novel toxins. We continue to isolate and
identify structurally and/or functionally unique toxins from venomous
animals.
Research accomplishments:
-
Shown structural features in the
flanking segments of protein-protein interaction sites.
-
Determined structure-function relationships
and mechanism of PLA2 enzymes.
-
dentified common cytolytic region
in proteins.
-
Identified the structure-function
relationships of three-finger toxins and solved the mechanism
of antiplatelet effects of cardiotoxins.
-
Determined structure of prothrombin
activators and designed anticoagulant peptides.
List of publications
23 Patent applications, over 110 research
publications and 2 books.
Book: Venom Phospholipase A2 Enzymes: Structure,
Function and Mechanism (Kini, R.M., Editor), Pg. 1-511, John Wiley
& Sons, Chichester, England, 1997. |
