Isolation and characterization of an angiotensin converting enzyme substrate from vitellogenic ovaries of Neobellieria bullata.
Vitellogenic ovaries of the gray fleshfly Neobellieria bullata contain a variety of unidentified substances that interact, either as a substrate or as an inhibitor, with angiotensin converting enzyme (ACE). We here report the isolation and characterization of the first ACE interactive compound hereof. This 1312.7 Da peptide with the sequence NKLKPSQWISL, is substrate to both insect and human ACE. It is a novel peptide that shows high sequence similarity to a sequence at the N-terminal part of dipteran yolk polypeptides (YPs). We propose to call it N. bullata ovary-derived ACE interactive factor or Neb-ODAIF. Both insect and human ACE hydrolyze Neb-ODAIF by sequentially cleaving off two C-terminal dipeptides. K(m) values of Neb-ODAIF and Neb-ODAIF(1-9) (NKLKPSQWI) for human somatic ACE (sACE) are 17 and 81 microM, respectively. Additionally, Neb-ODAIF(1-7) (NKLKPSQ) also interacts with sACE (K(m/i)=90 microM). These affinity-constants are in range with those of the physiological ACE substrates and suggest the importance of Neb-ODAIF and its cleavage products in the elucidation of the physiological role of insect ACE. Alternatively, they can serve as lead compounds in the development of new drugs against ACE-related diseases in humans.
Vandingenen
Anick
A
Laboratory of Developmental Physiology and Molecular Biology, Zoological Institute of the Catholic University of Leuven, Naamsestraat 59, B-3000 Leuven, Belgium. anick.vandingenen@bio.kuleuven.ac.be
Hens
Korneel
K
Baggerman
Geert
G
Macours
Nathalie
N
Schoofs
Liliane
L
De Loof
Arnold
A
Huybrechts
Roger
R
D000595:Amino Acid Sequence; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D016466:CHO Cells; D002216:Captopril / Q000494:pharmacology; D006224:Cricetinae; D004175:Diptera / Q000201:enzymology*; D004527:Egg Proteins / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism; D005260:Female; D006458:Hemolymph / Q000378:metabolism; D006868:Hydrolysis; D019476:Insect Proteins / Q000737:chemistry* / Q000378:metabolism; D007700:Kinetics; D008970:Molecular Weight; D009842:Oligopeptides / Q000737:chemistry / Q000378:metabolism; D010053:Ovary / Q000201:enzymology* / Q000378:metabolism; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D013045:Species Specificity; D013379:Substrate Specificity
D000806:Angiotensin-Converting Enzyme Inhibitors; D004527:Egg Proteins; D019476:Insect Proteins; C474276:Neb-ODAIF; D009842:Oligopeptides; D011994:Recombinant Proteins; D002216:Captopril; D007703:Peptidyl-Dipeptidase A