Kwong A D, Kim J L, Lin C
Vertex Pharmaceuticals, Inc., Cambridge, MA 02139, USA.
Curr Top Microbiol Immunol. 2000;242:171-96. doi: 10.1007/978-3-642-59605-6_9.
Hepatitis C Virus helicase activity has been mapped to the COOH-terminal 450 residues of the NS3 protein. Due to its complexity and presumed essentiality for viral replication, the helicase is an attractive target for drug discovery. The elucidation of the atomic structure of the HCV NS3 helicase in complex with oligonucleotide and with ADP has helped clarify our understanding of potential sites for inhibitor binding. Molecular details of the mechanism of this enzyme, and in particular, a better understanding of the mechanism by which ATP hydrolysis is coupled to unwinding of double-stranded substrate may facilitate more efficient structure-based drug design.
丙型肝炎病毒解旋酶活性已定位到NS3蛋白的C末端450个残基。由于其复杂性以及对病毒复制的假定必要性,解旋酶是药物研发的一个有吸引力的靶点。丙型肝炎病毒NS3解旋酶与寡核苷酸和ADP复合物的原子结构的阐明,有助于我们更清楚地了解抑制剂结合的潜在位点。该酶机制的分子细节,尤其是对ATP水解与双链底物解旋偶联机制的更好理解,可能有助于更高效的基于结构的药物设计。