3-DIMENSIONAL STRUCTURE OF A TRANSGLUTAMINASE - HUMAN BLOOD-COAGULATION FACTOR-XIII

Mechanical stability in many biological materials is provided by the c rosslinking of large structural proteins with gamma-glutamyl-epsilon-l ysyl amide bonds. The three-dimensional structure of human recombinant factor XIII (EC 2.3.2.13 zymogen; protein-glutamine:amine gamma-gluta myltransferase a chain), a transglutaminase zymogen, has been solved a t 2.8-Angstrom resolution by x-ray crystallography. This structure sho ws that each chain of the homodimeric protein is folded into four sequ ential domains. A catalytic triad reminiscent of that observed in cyst eine proteases has been identified in the core domain. The amino-termi nal activation peptide of each subunit crosses the diner interface and partially occludes the opening of the catalytic cavity in the second submit, preventing substrate binding to the zymogen. A proposal for th e mechanism of activation by thrombin and calcium is made that details the structural events leading to active factor XIIIa'.