The human blood coagulation factor XIII A-subunit dimer structure, as determined by our X-ray crystallography efforts. Each subunit contains 730 amino acid residues and the total formula weight is 166,000 daltons.
"The Most Important Molecule in the World" -dct
At the current time we are continuing our crystallographic studies of human coagulation factor XIII, an important blood coagulation protein, by the methods of X-ray diffraction.
Activated factor XIII is the prototypical enzyme of a family of transglutaminases and related proteins found universally among animals. These large proteins are intimately involved in formation of skin and hair, in blood coagulation, in fertilization events, and in several disease states as well. Factor XIII is activated to factor XIIIa by thrombin in the final step of the coagulation cascade. Factor XIIIa is a transglutaminase serving to cross-link fibrin to form a stable clot. Additionally, factor XIIIa performs other cross-linking functions which promote wound healing.
The zymogen, factor XIII, has been used in our published crystallization studies to date. The human zymogen is synthesized by the yeast, Saccharomyces cerevesiae. The molecule is a dimer of molecule mass 166 kDa with 730 residues per monomer. We have now determined the structures of the zymogen in two crystal forms, and also after thrombin-cleavage. Current efforts are directed to the study of site specific mutant forms of the protein, to crystallization studies of the thrombin activated enzyme, and to study of inhibited forms of the enzyme and zymogen activated by high calcium ion concentrations.
In addition to the investigations of factor XIII, we are engaged in crystallographic studies of several other coagulation factors and inhibitors of those factors.