Hydrolysis of biological peptides by human angiotensin-converting enzyme-related carboxypeptidase. Export

@article{citeulike:264025, abstract = {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.}, address = {Department of Metabolic Disease, Millennium Pharmaceuticals, Inc., Cambridge, Massachusetts 02139, USA.}, author = {Vickers, C. and Hales, P. and Kaushik, V. and Dick, L. and Gavin, J. and Tang, J. and Godbout, K. and Parsons, T. and Baronas, E. and Hsieh, F. and Acton, S. and Patane, M. and Nichols, A. and Tummino, P.}, citeulike-article-id = {264025}, citeulike-linkout-0 = {http://dx.doi.org/10.1074/jbc.M200581200}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/11815627}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=11815627}, day = {26}, doi = {10.1074/jbc.M200581200}, issn = {0021-9258}, journal = {J Biol Chem}, keywords = {ace2}, month = {April}, number = {17}, pages = {14838--14843}, posted-at = {2005-07-25 08:24:03}, priority = {2}, title = {Hydrolysis of biological peptides by human angiotensin-converting enzyme-related carboxypeptidase.}, url = {http://dx.doi.org/10.1074/jbc.M200581200}, volume = {277}, year = {2002} }

TY - JOUR ID - citeulike:264025 L3 - citeulike-article-id:264025 N2 - 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. IS - 17 JF - J Biol Chem SN - 0021-9258 AD - Department of Metabolic Disease, Millennium Pharmaceuticals, Inc., Cambridge, Massachusetts 02139, USA. EP - 14843 TI - Hydrolysis of biological peptides by human angiotensin-converting enzyme-related carboxypeptidase. VL - 277 SP - 14838 KW - ace2 AU - Vickers, C AU - Hales, P AU - Kaushik, V AU - Dick, L AU - Gavin, J AU - Tang, J AU - Godbout, K AU - Parsons, T AU - Baronas, E AU - Hsieh, F AU - Acton, S AU - Patane, M AU - Nichols, A AU - Tummino, P PY - 2002/04/26/ UR - http://dx.doi.org/10.1074/jbc.M200581200 ER -