New feature of angiotensin-converting enzyme: carbohydrate-recognizing domain.
Self carbohydrate-mediated dimerization of glycoprotein angiotensin-converting enzyme (ACE) was demonstrated. The dimerization was studied in the reverse micelle experimental system as a model of biomembrane situation. Asialo-ACE or agalacto-ACE was able to form a dimer, whereas deglycosylated ACE and sequentially desialylated and degalactosylated ACE failed to dimerize. ACE-ACE interaction was competitively inhibited by Neu5Ac- or Gal-terminated saccharides. The results have allowed us to propose the existence of carbohydrate-recognizing domain (CRD) on ACE molecule. The structural requirements of this CRD were estimated based on the ability of saccharides to inhibit ACE dimerization. The most effective monosaccharides with equal inhibition potencies were shown to be galactose (as GalbetaOMe) and N-acetylneuraminic acid (as Neu5AcalphaOMe). Among oligosaccharides, the most effective ones were found to be 3'SiaLac and, especially, the whole pool of ACE oligosaccharide chains and biantennae complex oligosaccharide chains of other glycoproteins. Bovine and human ACEs were shown to be similar in terms of recognition of carbohydrates.
Kost
O A
OA
Chemistry Department, MV Lomonosov Moscow State University, Russia. kost@enzyme.chem.msu.ru
Bovin
N V
NV
Chemodanova
E E
EE
Nasonov
V V
VV
Orth
T A
TA
D000818:Animals; D001665:Binding Sites; D002236:Carbohydrate Conformation; D050260:Carbohydrate Metabolism; D002417:Cattle; D019281:Dimerization; D005690:Galactose / Q000737:chemistry; D006801:Humans; D009005:Monosaccharides / Q000378:metabolism; D019158:N-Acetylneuraminic Acid / Q000737:chemistry; D007703:Peptidyl-Dipeptidase A / Q000737:chemistry / Q000378:metabolism*; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D014461:Ultracentrifugation
D009005:Monosaccharides; D007703:Peptidyl-Dipeptidase A; D019158:N-Acetylneuraminic Acid; D005690:Galactose