The Crystal Structure of the Hepatitis C Virus NS3 RNA Helicase at 1.5 Å Resolution

 

Hsin-Mao Chu1, Shwu-Huey Liaw1,2, Li-Hua Huang3, and Ding-Shinn Chen3*

 1 Institute of Biochemistry; 2 Department of Life Science, National Yang-Ming University; and 3Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan.

 

The crystal structure of NS3 helicase domain from a Taiwanese strain hepatitis C virus has been determined at 1.5 Å resolution. The conserved motifs form an extensive interaction network, implying that these motifs cooperatively constitute a large functional active site rather than act as individual. Comparison to the previously solved structures reveals two conformations, suggesting that domain movement could be performed by a rigid-body rotation of domain 2 to the domains 1 and 3 through four hinges. Formation of this more open conformation may be resulted from the presence of high salts or due to the crystal packing. Crystals grown in the presence of the inhibitor poly(U) and the cofactor NTP analogues showed neither substrate bound at the active site, and then suggested that the domain 2 participates not only the nucleic acid but also the NTP binding. Some regions showed conformational differences, particularly the P-loop forming a giant anion hole. Finally, comparison to the DNA helicase PcrA revealed a putative double-stranded nucleic acid-binding site on domain 3

 

 

 

 

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