On the inhibition mechanism of the sialidase activity from Newcastle disease virus.
N-Acetylneuraminic, 2-deoxy-2,3-didehydro-N-acetylneuraminic acid and the beta anomer of methoxyneuraminic acid (Neu5Ac, Neu5Ac2en, MeONeu) have been used as probes for the catalytic mechanism of the activities of the outer membrane-bound haemagglutinin-neuraminidase (HN) from newcastle disease virus (NDV). Neu5Ac and Neu5Ac2en produced a competitive inhibition of the sialidase (= neuraminidase) activity, whereas MeONeu had no effect on this activity. This lack of inhibition can be explained by the free amino-acid group lacking the acetyl substituent in the MeONeu. Neu5Ac2en produced the highest inhibition. Based on the effect of the inhibitors, a reaction mechanism is suggested. On the other hand, the above mentioned inhibitors of the sialidase activity had no effect on haemagglutinating activity, suggesting different active sites for the both activities.
García Sastre
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Departamento de Bioquímica y Biología Molecular, Facultad de Biología, Universidad de Salamanca, Spain.
Cobaleda
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Cabezas
J A
JA
Villar
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D015707:HN Protein / Q000187:drug effects; D006385:Hemagglutination Inhibition Tests; D006387:Hemagglutination, Viral / Q000187:drug effects; D007700:Kinetics; D019158:N-Acetylneuraminic Acid / Q000031:analogs & derivatives; D009438:Neuraminic Acids / Q000494:pharmacology; D009439:Neuraminidase / Q000037:antagonists & inhibitors*; D009522:Newcastle disease virus / Q000201:enzymology*; D012794:Sialic Acids / Q000494:pharmacology*
D015707:HN Protein; D009438:Neuraminic Acids; D012794:Sialic Acids; C036137:2-deoxy-2,3-dehydro-N-acetylneuraminic acid; C072466:2-methoxyneuraminic acid; D009439:Neuraminidase; D019158:N-Acetylneuraminic Acid