A Zinc Binding Site in Viral Serine Proteinases
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- 作者：Raffaele De Francesco ; Andrea Urbani ; Maria Chiara Nardi ; Licia Tomei ; Christian Steinkü ; hler ; and Anna Tramontano
- 刊名：Biochemistry
- 出版年：1996
- 出版时间：October 15, 1996
- 年：1996
- 卷：35
- 期：41
- 页码：13282 - 13287
- 全文大小：340K
- 年卷期：v.35,no.41(October 15, 1996)
- ISSN：1520-4995
文摘
The NS3 protein of hepatitis C virus contains achymotrypsin-like serine proteinase domain.We built a homology model of this domain which predicts thepresence of a tetradentate metal bindingsite formed by three cysteines and one histidine. These residuesare strictly conserved in all knownhepatitis C viral genotypes as well as in other recently discoveredrelated hepatitis viruses. We show thatthe hepatitis C virus enzyme does indeed contain a Zn2+ion with S3N ligation and that the metal isrequired for structural integrity and activity of the enzyme.Strikingly, the residues forming the metalbinding site are also conserved in the chymotrypsin-like 2A cysteineproteinases of picornaviruses.Remarkably, in these highly variable viral genomes the metalbinding site is more conserved than thecatalytic residues and thus allows us to define a novel class of zincbinding chymotrypsin-like proteinasesand to identify a new attractive target for antiviraltherapy.