5E4F

The spring alpha-helix coordinates multiple modes of HCV NS3 helicase action

5E4F の概要

• エントリーDOI: 10.2210/pdb5e4f/pdb
• 分子名称: Serine protease NS3, TETRAFLUOROALUMINATE ION, ADENOSINE-5'-DIPHOSPHATE, ... (5 entities in total)
• 機能のキーワード: hcv ns3 helicase, transition state, hydrolase
• 由来する生物種: Hepatitis C virus genotype 1b (isolate Con1) (HCV)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 94593.08

構造登録者

Gu, M.,Rice, C.M. (登録日: 2015-10-05, 公開日: 2016-05-18, 最終更新日: 2024-03-06)

主引用文献

Gu, M.,Rice, C.M.
The Spring alpha-Helix Coordinates Multiple Modes of HCV (Hepatitis C Virus) NS3 Helicase Action.
J.Biol.Chem., 291:14499-14509, 2016

PubMed Abstract: Genomic DNA replication requires helicases to processively unwind duplexes. Although helicases encoded by positive-strand RNA viruses are necessary for RNA genome replication, their functions are not well understood. We determined structures of the hepatitis C virus helicase (NS3h) in complex with the transition state ATP mimic ADP·AlF4 (-) and compared them with the previous nucleic acid-associated ternary complexes. The results suggested that nucleic acid binding promotes a structural change of the spring helix at the transition state, optimizing the interaction network centered on the nucleophilic water. Analysis of ATP hydrolysis with and without conformational restraints on the spring helix further supported the importance of its action for both nucleic acid-stimulated and basal catalysis. We further found that an F238P substitution, predicted to destabilize the helix, diminished viral RNA replication without significantly affecting ATP-dependent duplex unwinding. The stability of the secondary structure, thus, seems critical for additional functions of NS3h. Taken together, the results suggest that the spring helix may be central to the coordination of multiple modes of NS3h action. Further characterization centered on this element may help understand the molecular details of how the viral helicase facilitates RNA replication. This new structural information may also aid efforts to develop specific inhibitors targeting this essential viral enzyme.

PubMed: 27226535
DOI: 10.1074/jbc.M115.704379

実験手法

X-RAY DIFFRACTION (2.1 Å)