Our research is focused on enzymes involved in blood coagulation and related processes. Members of this critical protein cascade have far reaching effects on wound healing, heart disease, stroke, and cancer. Further knowledge is still needed on the activation and the substrate/ligand binding properties of individual enzymes. In our laboratory, emphasis has been placed on examining the transglutaminase Factor XIII (FXIII) and the serine protease thrombin. Activated FXIII catalyzes the formation of covalent cross-links within the fibrin blood clot network. Thrombin is involved in converting fibrinogen into fibrin and in activating a variety of enzymes including FXIII and the protease activated receptors found in platelets. In our research studies, we employ a combination of kinetic measurements, solution NMR studies, and mass spectrometry approaches. Greater understanding of the structural and biological features of FXIII and thrombin may lead to novel medical strategies to control the actions of these vital proteins and the resultant clot architecture.