期刊
JOURNAL OF GENERAL VIROLOGY
卷 89, 期 -, 页码 636-641出版社
SOC GENERAL MICROBIOLOGY
DOI: 10.1099/vir.0.83359-0
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资金
- NATIONAL CENTER FOR RESEARCH RESOURCES [U54RR020843] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES [P01AI055789] Funding Source: NIH RePORTER
- NCRR NIH HHS [RR020843, U54 RR020843] Funding Source: Medline
- NIAID NIH HHS [AI055789, P01 AI055789] Funding Source: Medline
- NIMH NIH HHS [X01MH077601] Funding Source: Medline
West Nile virus (WNV) is an emerging mosquito-borne flavivirus that causes neuronal damage in the absence of treatment. In many flaviviruses, including WNV, the NS2B cofactor promotes the productive folding and the functional activity of the two-component NS3 (pro)teinase. Based on an analysis of the NS2B - NS3pro structure, we hypothesized that the G(22) residue and the negatively charged patch (DDD34)-D-32 of NS2B were part of an important configuration required for NS2B - NS3pro activity. Our experimental data confirmed that G(22) and (DDD34)-D-32 substitution for S and AAA, respectively, inactivated NS2B - NS3pro. An additional D42G mutant, which we designed as a control, had no dramatic effect on either the catalytic activity or self-proteolysis of NS2B - NS3pro. Because of the significant level of homology in flaviviral NS2B - NS3pro, our results will be useful for the development of specific allosteric inhibitors designed to interfere with the productive interactions of NS2B with NS3pro.
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