Sampath Aruna, Xu Ting, Chao Alex, Luo Dahai, Lescar Julien, Vasudevan Subhash G
School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, Singapore 637551, Singapore.
J Virol. 2006 Jul;80(13):6686-90. doi: 10.1128/JVI.02215-05.
We performed a mutational analysis of the NS3 helicase of dengue virus to test insights gleaned from its crystal structure and identified four residues in the full-length protein that severely impaired either its RTPase and ATPase (Arg-457-458, Arg-460, Arg-463) or helicase (Ile-365, Arg-376) activity. Alanine substitution of Lys-396, which is located at the surface of domain II, drastically reduced all three enzymatic activities. Our study points to a pocket at the surface of domain II that may be suitable for the design of allosteric inhibitors.
我们对登革热病毒的NS3解旋酶进行了突变分析,以检验从其晶体结构中获得的见解,并在全长蛋白中鉴定出四个严重损害其RTP酶和ATP酶(Arg-457-458、Arg-460、Arg-463)或解旋酶(Ile-365、Arg-376)活性的残基。位于结构域II表面的Lys-396被丙氨酸取代后,所有三种酶活性都大幅降低。我们的研究指出了结构域II表面的一个口袋,它可能适合设计变构抑制剂。