Influenza C virus and bovine coronavirus esterase reveal a similar catalytic mechanism: new insights for drug discovery.
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| Abstract |
Both, the influenza C (INF-C) virus haemagglutinin esterase fusion and bovine coronavirus (BCoV) haemagglutinin esterase surface glycoproteins exhibit a lectin binding capability and a receptor-destroying 9-O-acetyl esterase activity that recognise 9-O-acetyl-N-acetylneuraminic acid (Neu5,9Ac(2))-containing glycans. Here we report nuclear magnetic resonance and molecular modelling studies on the 9-O-acetyl esterase showing that the alpha-configured Neu5,9Ac(2) is strictly preferred by the INF-C and BCoV esterases. Interestingly, we have discovered that the INF-C esterase function releases acetate independently of the chemical nature of the aglycon moiety, whereas subtle differences in substrate recognition were found for BCoV esterase. Analysis of the apo and complexed X-ray crystal structure of INF-C esterase revealed that binding of 9-O-acetylated N-acetylneuraminic acids is a dynamic process that involves conformational rearrangement of serine-57 in the esterase active site. This study provides valuable insights towards the design of drugs to combat INF-C virus and coronavirus infections causing outbreaks of upper respiratory infections and severe diarrhea in calves, respectively.
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| Authors | Juliane Mayr, Thomas Haselhorst, Martijn A Langereis, Jeffrey C Dyason, Wolfgang Huber, Barbara Frey, Reinhard Vlasak, Raoul J de Groot, Mark von Itzstein |
| Journal | Glycoconjugate journal (Glycoconj J) Vol. 25 Issue 5 Pg. 393-9 (Jul 2008) ISSN: 0282-0080 [Print] United States |
| PMID | 18196455 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't) |
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