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.
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).
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)
