Non-specific (model) peptide hydrolysis by enteropeptidase and its possible physiological role

Likhareva V.V.1, Mikhailova A.G.1, Rumsh L.D.1

1. Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences
PubMed Id: 12698555
Year: 2002  Volume: 48  Issue: 6  Pages: 561-569
Enteropeptidase (enterokinase) (EC, a highly specific processing protease, initiating a cascade of reactions activating the digestion enzymes. Сatalyzing trypsinogen activation еnteropeptidase exhibits unique properties for high efficiency hydrolysis of the polypeptide chain after lysine-15 residue in the –DDDDK15- sequence. In 1998 we found an unusual calcium-dependent autolysis of the enteropeptidase heavy chain leading to the drastic loss of its activity towards trypsinogen: after lysine-360 (-NNYEK360-INCN-), -), arginine-384 (-NEWER384-TQGS-), arginine-422 (-GRRER422-VGLL-) and lysine-465 (-QNMEK465-TIFQ-) residues. We used hepta-nona-peptides as the model substrates for autolysys: human angiotensin II - DRVYIHPF and cattle hemoglobin b-chain fragments: LTAEEKA and MLTAEEKAA. Kinetic parameters of enteropeptidase hydrolysis for these substrates were determined. Recent study demonstrates the ability of enteropeptidase to hydrolyze peptide bonds formed by carboxyl groups of Lys or Arg residues if less than four but at least one negative charged amino acid residue is in any of substrate Р2 - Р5 positions. Ca2+-dependent autolysis of enteropeptidase heavy chain and of trypsin were compared; the second one serves as the natural defense mechanism against the undesirable premature proenzymes activation in pancreas leading to pancreatitis. The corresponding enteropeptidase inactivation in low Ca2+environment ought to be the component of the same protective mechanism
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Likhareva, V. V., Mikhailova, A. G., Rumsh, L. D. (2002). Non-specific (model) peptide hydrolysis by enteropeptidase and its possible physiological role. Voprosy Meditsinskoi Khimii, 48(6), 561-569.
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