Hydrolysis of Biological Peptides by Human Angiotensin-converting Enzyme-related Carboxypeptidase
| Autor: | Larry Dick, Virendar K. Kaushik, Thomas F. Parsons, Peter J. Tummino, Susan L. Acton, Michael A. Patane, Kevin Godbout, Jin Tang, Elizabeth Baronas, Chad S Vickers, Frank Y. Hsieh, James M. Gavin, Paul Hales, Andrew J. Nichols |
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| Rok vydání: | 2002 |
| Předmět: |
Stereochemistry
Peptide Carboxypeptidases Peptidyl-Dipeptidase A Biochemistry Catalysis Humans Amino Acid Sequence Molecular Biology Peptide sequence Chromatography High Pressure Liquid chemistry.chemical_classification biology Hydrolysis Angiotensin-converting enzyme Cell Biology Hydrogen-Ion Concentration Chromatography Ion Exchange Carboxypeptidase Angiotensin II Recombinant Proteins Amino acid Kinetics Enzyme chemistry Spectrometry Mass Matrix-Assisted Laser Desorption-Ionization Angiotensin-converting enzyme 2 biology.protein Spectrophotometry Ultraviolet Angiotensin-Converting Enzyme 2 Peptides hormones hormone substitutes and hormone antagonists |
| Zdroj: | Journal of Biological Chemistry. 277:14838-14843 |
| ISSN: | 0021-9258 |
| Popis: | Human angiotensin-converting enzyme-related carboxypeptidase (ACE2) is a zinc metalloprotease whose closest homolog is angiotensin I-converting enzyme. To begin to elucidate the physiological role of ACE2, ACE2 was purified, and its catalytic activity was characterized. ACE2 proteolytic activity has a pH optimum of 6.5 and is enhanced by monovalent anions, which is consistent with the activity of ACE. ACE2 activity is increased approximately 10-fold by Cl(-) and F(-) but is unaffected by Br(-). ACE2 was screened for hydrolytic activity against a panel of 126 biological peptides, using liquid chromatography-mass spectrometry detection. Eleven of the peptides were hydrolyzed by ACE2, and in each case, the proteolytic activity resulted in removal of the C-terminal residue only. ACE2 hydrolyzes three of the peptides with high catalytic efficiency: angiotensin II () (k(cat)/K(m) = 1.9 x 10(6) m(-1) s(-1)), apelin-13 (k(cat)/K(m) = 2.1 x 10(6) m(-1) s(-1)), and dynorphin A 1-13 (k(cat)/K(m) = 3.1 x 10(6) m(-1) s(-1)). The ACE2 catalytic efficiency is 400-fold higher with angiotensin II () as a substrate than with angiotensin I (). ACE2 also efficiently hydrolyzes des-Arg(9)-bradykinin (k(cat)/K(m) = 1.3 x 10(5) m(-1) s(-1)), but it does not hydrolyze bradykinin. An alignment of the ACE2 peptide substrates reveals a consensus sequence of: Pro-X((1-3 residues))-Pro-Hydrophobic, where hydrolysis occurs between proline and the hydrophobic amino acid. |
| Databáze: | OpenAIRE |
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