| Abstract: | It has been shown for the first time that deacylation is the rate-limiting stage in the enteropeptidase-catalyzed hydrolysis of highly efficient oligopeptide substrates containing four Asp residues in positions P2-P5. On the other hand, the rate-limiting stage in the hydrolysis of low-efficiency peptide substrates containing less than four Asp or Glu residues in positions P2-P5 is acylation, as has previously been suggested for all amide and peptide substrates of serine proteases on the basis of the classic studies by Bender et al. The method of introduction of an additional nucleophile or another effector that selectively affects the deacylation stage was used to determine the rate-limiting stage in the enteropeptidase hydrolysis of Nalpha-benzyloxycarbonyl-L-lysine thiobenzyl ester, the highly efficient amide substrate GlyAsp4-Lys beta-naphthyl amide, and the low-efficiency peptide substrate VLSAADK-GNVKAAWG (where a hyphen denotes the hydrolysis site). The English version of the paper: Russian Journal of Bioorganic Chemistry, 2008, vol. 34, no. 2; see also http://www.maik.ru. |
