1DXW

structure of hetero complex of non structural protein (NS) of hepatitis C virus (HCV) and synthetic peptidic compound

1DXW の概要

• エントリーDOI: 10.2210/pdb1dxw/pdb
• 関連するPDBエントリー: 1BT7
• NMR情報: BMRB: 4617
• 関連するBIRD辞書のPRD_ID: PRD_000426
• 分子名称: SERINE PROTEASE, N-(tert-butoxycarbonyl)-L-alpha-glutamyl-N-[(1R)-1-(carboxycarbonyl)-3,3-difluoropropyl]-L-leucinamide, ZINC ION (3 entities in total)
• 機能のキーワード: non structural protein, hepatitis c virus, serine protease, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• 由来する生物種: HEPATITIS C VIRUS (HCV)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 20209.44

構造登録者

Barbato, G.,Cicero, D.O.,Cordier, F.,Narjes, F.,Gerlach, B.,Sambucini, S.,Grzesiek, S.,Matassa, V.G.,Defrancesco, R.,Bazzo, R. (登録日: 2000-01-17, 公開日: 2001-01-12, 最終更新日: 2024-11-13)

主引用文献

Barbato, G.,Cicero, D.O.,Cordier, F.,Narjes, F.,Gerlach, B.,Sambucini, S.,Grzesiek, S.,Matassa, V.G.,Defrancesco, R.,Bazzo, R.
Inhibitor Binding Induces Active Site Stabilisation of the Hcv Ns3 Protein Serine Protease Domain
Embo J., 19:1195-, 2000

PubMed Abstract: Few structures of viral serine proteases, those encoded by the Sindbis and Semliki Forest viruses, hepatitis C virus (HCV) and cytomegalovirus, have been reported. In the life cycle of HCV a crucial role is played by a chymotrypsin-like serine protease encoded at the N-terminus of the viral NS3 protein, the solution structure of which we present here complexed with a covalently bound reversible inhibitor. Unexpectedly, the residue in the P2 position of the inhibitor induces an effective stabilization of the catalytic His-Asp hydrogen bond, by shielding that region of the protease from the solvent. This interaction appears crucial in the activation of the enzyme catalytic machinery and represents an unprecedented observation for this family of enzymes. Our data suggest that natural substrates of this serine protease could contribute to the enzyme activation by a similar induced-fit mechanism. The high degree of similarity at the His-Asp catalytic site region between HCV NS3 and other viral serine proteases suggests that this behaviour could be a more general feature for this category of viral enzymes.

PubMed: 10716920
DOI: 10.1093/EMBOJ/19.6.1195

実験手法

SOLUTION NMR