Date on Master's Thesis/Doctoral Dissertation
Committee Co-Chair (if applicable)
FXIII; monodansylcadaverine; transglutaminase; thrombin; Cab3
Factor XIII (FXIII) is an emerging target for treating blood clotting and cardiovascular related diseases. FXIII can be activated non-proteolytically by the presence of elevated Ca2+ levels (2-100 mM) or proteolytically by thrombin-cleavage of the Activation Peptide along with low mM Ca2+. The studies herein utilized fluorescence to examine how monovalent and divalent ions influence the transglutaminase activity and conformation of FXIII. Monodansylcadaverine assays revealed that increasing ionic radius (Cs+ > K+ > Na+ > Li+) and increasing ionic strength (XCl- levels and SO42- > Cl-) elevated FXIII-A transglutaminase activity. Intrinsic fluorescence studies revealed that only cations influenced FXIII conformation. For divalent salts, transglutaminase activity for MgSO4 is ~3-fold higher than MgCl2. Unlike transglutaminase 2, FXIII containing a mutation in the Cab3 calcium binding site (G262V) could not exhibit an improvement in activity. A FXIII Cab3 helix is proposed to be hindered which impacts non-proteolytically activated FXIII more than proteolytically activated FXIII. Both cations and anions influence FXIII’s ability to interact with substrates.
Lumata, Richard Laporca, "Effects of monovalent and divalent ions in factor xiii activation and crosslinking." (2022). Electronic Theses and Dissertations. Paper 3969.