RGD Reference Report - Novel natural peptide substrates for endopeptidase 24.15, neurolysin, and angiotensin-converting enzyme. - Rat Genome Database

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Novel natural peptide substrates for endopeptidase 24.15, neurolysin, and angiotensin-converting enzyme.

Authors: Rioli, Vanessa  Gozzo, Fabio C  Heimann, Andrea S  Linardi, Alessandra  Krieger, José E  Shida, Cláudio S  Almeida, Paulo C  Hyslop, Stephen  Eberlin, Marcos N  Ferro, Emer S 
Citation: Rioli V, etal., J Biol Chem. 2003 Mar 7;278(10):8547-55. doi: 10.1074/jbc.M212030200. Epub 2002 Dec 24.
RGD ID: 152025518
Pubmed: PMID:12500972   (View Abstract at PubMed)
DOI: DOI:10.1074/jbc.M212030200   (Journal Full-text)

Endopeptidase 24.15 (EC; ep24.15), neurolysin (EC; ep24.16), and angiotensin-converting enzyme (EC; ACE) are metallopeptidases involved in neuropeptide metabolism in vertebrates. Using catalytically inactive forms of ep24.15 and ep24.16, we have identified new peptide substrates for these enzymes. The enzymatic activity of ep24.15 and ep24.16 was inactivated by site-directed mutagenesis of amino acid residues within their conserved HEXXH motifs, without disturbing their secondary structure or peptide binding ability, as shown by circular dichroism and binding assays. Fifteen of the peptides isolated were sequenced by electrospray ionization tandem mass spectrometry and shared homology with fragments of intracellular proteins such as hemoglobin. Three of these peptides (PVNFKFLSH, VVYPWTQRY, and LVVYPWTQRY) were synthesized and shown to interact with ep24.15, ep24.16, and ACE, with K(i) values ranging from 1.86 to 27.76 microm. The hemoglobin alpha-chain fragment PVNFKFLSH, which we have named hemopressin, produced dose-dependent hypotension in anesthetized rats, starting at 0.001 microg/kg. The hypotensive effect of the peptide was potentiated by enalapril only at the lowest peptide dose. These results suggest a role for hemopressin as a vasoactive substance in vivo. The identification of these putative intracellular substrates for ep24.15 and ep24.16 is an important step toward the elucidation of the role of these enzymes within cells.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
peptide catabolic process involved_inIDA 152025518; 152025518PMID:12500972UniProt 

Molecular Function
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
peptidase activity enablesIDA 152025518; 152025518; 152025518PMID:12500972UniProt 

Objects Annotated

Genes (Rattus norvegicus)
Ace  (angiotensin I converting enzyme)
Nln  (neurolysin)
Thop1  (thimet oligopeptidase 1)


Additional Information