Tissue transglutaminase acylation: Proposed role of conserved active site Tyr and Trp residues revealed by molecular modeling of peptide substrate binding.

ABSTRACT: Transglutaminases (TGases) catalyze the cross-linking of peptides and proteins by the formation of gamma-glutamyl-epsilon-lysyl bonds. Given the implication of tissue TGase in various physiological disorders, development of specific tissue TGase inhibitors is of current interest. To aid in the design of peptide-based inhibitors, a better understanding of the mode of binding of model peptide substrates to the enzyme is required. Using a combined kinetic/molecular modeling approach, we have generated a model for the binding of small acyl-donor peptide substrates to tissue TGase from red sea bream. Kinetic analysis of various N-terminally derivatized Gln-Xaa peptides has demonstrated that many CBz-Gln-Xaa peptides are typical in vitro substrates with K(M) values between 1.9 mM and 9.4 mM, whe

SUBMITTER: Chica RA 

PROVIDER: S-EPMC2280066 | biostudies-literature | 2004 Apr

REPOSITORIES: biostudies-literature