Characterizing the specificity of activated Factor XIII for glutamine-containing substrate peptides

摘要: Abstract Activated Factor XIII (FXIIIa) is a transglutaminase that catalyzes the formation of γ-glutamyl-ɛ-lysine crosslinks in fibrin network. To better understand source FXIIIa substrate specificity, Q-containing substrates based on β-casein, K9-peptide, and α2-antiplasmin were characterized. α2AP (1–15, Q2, Q4) Q4N, K12R) are highly promising peptide models since they exhibited kcat/Km values comparable to intact β-casein. In absence lysine-like donor, could promote deamidation reactive Q an E solution NMR served as effective strategy for monitoring this reaction. A tendency toward allowed greater investigations peptides. preferentially selects Q2 residue carrying out crosslinking processes. The E3 Q4 provide supporting roles binding. When reaction occurs at position sterically blocked from reactivity. By contrast, E2 allows, first time, observation reactivity Q4. K12 provides additional favorable site interaction with surface. sensitivity amino acid changes Q4, suggests importance individual subsites controlled by chemical environment sterics.