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dc.contributor.authorRobin, Gautier
dc.contributor.authorChappell, Keith
dc.contributor.authorStoermer, Martin J
dc.contributor.authorHu, Shu-Hong
dc.contributor.authorYoung, Paul R
dc.contributor.authorFairlie, David P
dc.contributor.authorMartin, Jennifer L
dc.date.accessioned2017-09-22T03:46:03Z
dc.date.available2017-09-22T03:46:03Z
dc.date.issued2009
dc.identifier.issn0022-2836
dc.identifier.doi10.1016/j.jmb.2008.11.026
dc.identifier.urihttp://hdl.handle.net/10072/347145
dc.description.abstractOver the last decade, West Nile virus has spread rapidly via mosquito transmission from infected migratory birds to humans. One potential therapeutic approach to treating infection is to inhibit the virally encoded serine protease that is essential for viral replication. Here we report the crystal structure of the viral NS3 protease tethered to its essential NS2B cofactor and bound to a potent substrate-based tripeptide inhibitor, 2-naphthoyl-Lys-Lys-Arg-H (Ki = 41 nM), capped at the N-terminus by 2-naphthoyl and capped at the C-terminus by aldehyde. An important and unexpected feature of this structure is the presence of two conformations of the catalytic histidine suggesting a role for ligand stabilization of the catalytically competent His conformation. Analysis of other West Nile virus NS3 protease structures and related serine proteases supports this hypothesis, suggesting that the common catalytic mechanism involves an induced-fit mechanism.
dc.description.peerreviewedYes
dc.languageEnglish
dc.publisherElsevier
dc.relation.ispartofpagefrom1568
dc.relation.ispartofpageto1577
dc.relation.ispartofissue5
dc.relation.ispartofjournalJournal of Molecular Biology
dc.relation.ispartofvolume385
dc.subject.fieldofresearchBiochemistry and Cell Biology not elsewhere classified
dc.subject.fieldofresearchBiochemistry and Cell Biology
dc.subject.fieldofresearchMedicinal and Biomolecular Chemistry
dc.subject.fieldofresearchcode060199
dc.subject.fieldofresearchcode0601
dc.subject.fieldofresearchcode0304
dc.titleStructure of West Nile Virus NS3 Protease: Ligand Stabilization of the Catalytic Conformation
dc.typeJournal article
dc.type.descriptionC1 - Articles
dc.type.codeC - Journal Articles
gro.hasfulltextNo Full Text
gro.griffith.authorMartin, Jennifer


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