Source:http://linkedlifedata.com/resource/pubmed/id/11815627
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
17
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pubmed:dateCreated |
2002-4-22
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pubmed:abstractText |
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.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Carboxypeptidases,
http://linkedlifedata.com/resource/pubmed/chemical/Peptides,
http://linkedlifedata.com/resource/pubmed/chemical/Peptidyl-Dipeptidase A,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/angiotensin converting enzyme 2
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pubmed:status |
MEDLINE
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pubmed:month |
Apr
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pubmed:issn |
0021-9258
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pubmed:author |
pubmed-author:ActonSusanS,
pubmed-author:BaronasElizabethE,
pubmed-author:DickLarryL,
pubmed-author:GavinJamesJ,
pubmed-author:GodboutKevinK,
pubmed-author:HalesPaulP,
pubmed-author:KaushikVirendarV,
pubmed-author:KnabWW,
pubmed-author:NicholsAndrewA,
pubmed-author:ParsonsThomasT,
pubmed-author:PataneMichaelM,
pubmed-author:TangJinJ,
pubmed-author:TumminoPeterP,
pubmed-author:VickersChadC
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pubmed:issnType |
Print
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pubmed:day |
26
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pubmed:volume |
277
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
14838-43
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:11815627-Amino Acid Sequence,
pubmed-meshheading:11815627-Carboxypeptidases,
pubmed-meshheading:11815627-Catalysis,
pubmed-meshheading:11815627-Chromatography, High Pressure Liquid,
pubmed-meshheading:11815627-Chromatography, Ion Exchange,
pubmed-meshheading:11815627-Humans,
pubmed-meshheading:11815627-Hydrogen-Ion Concentration,
pubmed-meshheading:11815627-Hydrolysis,
pubmed-meshheading:11815627-Kinetics,
pubmed-meshheading:11815627-Peptides,
pubmed-meshheading:11815627-Peptidyl-Dipeptidase A,
pubmed-meshheading:11815627-Recombinant Proteins,
pubmed-meshheading:11815627-Spectrometry, Mass, Matrix-Assisted Laser...,
pubmed-meshheading:11815627-Spectrophotometry, Ultraviolet
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pubmed:year |
2002
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pubmed:articleTitle |
Hydrolysis of biological peptides by human angiotensin-converting enzyme-related carboxypeptidase.
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pubmed:affiliation |
Department of Metabolic Disease, Millennium Pharmaceuticals, Inc., Cambridge, Massachusetts 02139, USA.
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pubmed:publicationType |
Journal Article
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