Structural features of glutamine substrates for human plasma factor XIIIa (activated blood coagulation factor XIII).
The action of human plasma factor XIIIa (thrombin-activated blood coagulation factor XIII) and guinea pig liver transglutaminase on purified caseins, fibrin, the derivatized gamma chain of fibrin, and a number of synthetic glutamine peptides, and peptide derivatives is reported. There are wide variations in the properties of the individual proteins and peptides as substrates for amine incorporation by the two transglutaminases. beta-Casein and several of its derivatives are excellent substrates for factor XIIIa. However, beta-casein is a relatively poor substrate for the liver enzyme. The primary site of amine incorporation by factor XIIIa in beta-casein was identified as glutamine 167. This was accomplished by labeling with fluorescent amine followed by proteolytic digestion and identification of labeled peptides. An 11-residue peptide and a 15-residue peptide, each containing 1 glutamine residue and each modeled after the primary site of amine incorporation in beta-casein, were prepared. A 13-residue peptide modeled after the primary crosslinking site in fibrin gamma chain was also prepared. Each of these polypeptides proved to be an efficient substrate for factor XIIIa and displayed significantly better substrate properties than a number of small glutamine peptide derivatives that are good substrates for liver transglutaminase.
D000595:Amino Acid Sequence; D000596:Amino Acids / Q000032:analysis; D000818:Animals; D002364:Caseins; D005176:Factor XIII / Q000378:metabolism*; D005337:Fibrin; D005973:Glutamine; D006168:Guinea Pigs; D006801:Humans; D007700:Kinetics; D008099:Liver / Q000201:enzymology; D010446:Peptide Fragments / Q000032:analysis; D013379:Substrate Specificity; D014357:Trypsin; D005723:gamma-Glutamyltransferase / Q000378:metabolism
D000596:Amino Acids; D002364:Caseins; D010446:Peptide Fragments; D005973:Glutamine; D005337:Fibrin; D005176:Factor XIII; D005723:gamma-Glutamyltransferase; D014357:Trypsin