The crystal structure of hepatitis C virus NS3 proteinase reveals a trypsin-like fold and a structural zinc binding site - PubMed (original) (raw)
The crystal structure of hepatitis C virus NS3 proteinase reveals a trypsin-like fold and a structural zinc binding site
R A Love et al. Cell. 1996.
Free article
Abstract
During replication of hepatitis C virus (HCV), the final steps of polyprotein processing are performed by a viral proteinase located in the N-terminal one-third of nonstructural protein 3. The structure of NS3 proteinase from HCV BK strain was determined by X-ray crystallography at 2.4 angstrom resolution. NS3P folds as a trypsin-like proteinase with two beta barrels and a catalytic triad of His-57, Asp-81, Ser-139. The structure has a substrate-binding site consistent with the cleavage specificity of the enzyme. Novel features include a structural zinc-binding site and a long N-terminus that interacts with neighboring molecules by binding to a hydrophobic surface patch.
Similar articles
- The conformation of hepatitis C virus NS3 proteinase with and without NS4A: a structural basis for the activation of the enzyme by its cofactor.
Love RA, Parge HE, Wickersham JA, Hostomsky Z, Habuka N, Moomaw EW, Adachi T, Margosiak S, Dagostino E, Hostomska Z. Love RA, et al. Clin Diagn Virol. 1998 Jul 15;10(2-3):151-6. doi: 10.1016/s0928-0197(98)00036-1. Clin Diagn Virol. 1998. PMID: 9741640 - Crystal structure of the hepatitis C virus NS3 protease domain complexed with a synthetic NS4A cofactor peptide.
Kim JL, Morgenstern KA, Lin C, Fox T, Dwyer MD, Landro JA, Chambers SP, Markland W, Lepre CA, O'Malley ET, Harbeson SL, Rice CM, Murcko MA, Caron PR, Thomson JA. Kim JL, et al. Cell. 1996 Oct 18;87(2):343-55. doi: 10.1016/s0092-8674(00)81351-3. Cell. 1996. PMID: 8861917 - The hepatitis C virus NS3 proteinase: structure and function of a zinc-containing serine proteinase.
De Francesco R, Pessi A, Steinkühler C. De Francesco R, et al. Antivir Ther. 1998;3(Suppl 3):99-109. Antivir Ther. 1998. PMID: 10726060 Review. - Complex of NS3 protease and NS4A peptide of BK strain hepatitis C virus: a 2.2 A resolution structure in a hexagonal crystal form.
Yan Y, Li Y, Munshi S, Sardana V, Cole JL, Sardana M, Steinkuehler C, Tomei L, De Francesco R, Kuo LC, Chen Z. Yan Y, et al. Protein Sci. 1998 Apr;7(4):837-47. doi: 10.1002/pro.5560070402. Protein Sci. 1998. PMID: 9568891 Free PMC article. - Mechanisms of hepatitis C virus NS3 proteinase inhibitors.
De Francesco R, Pessi A, Steinkühler C. De Francesco R, et al. J Viral Hepat. 1999 Jul;6 Suppl 1:23-30. doi: 10.1046/j.1365-2893.1999.00002.x. J Viral Hepat. 1999. PMID: 10760031 Review.
Cited by
- Molecular and Dynamic Mechanism Underlying Drug Resistance in Genotype 3 Hepatitis C NS3/4A Protease.
Soumana DI, Kurt Yilmaz N, Ali A, Prachanronarong KL, Schiffer CA. Soumana DI, et al. J Am Chem Soc. 2016 Sep 14;138(36):11850-9. doi: 10.1021/jacs.6b06454. Epub 2016 Sep 2. J Am Chem Soc. 2016. PMID: 27512818 Free PMC article. - Taming a beast: lessons from the domestication of hepatitis C virus.
Luna JM, Saeed M, Rice CM. Luna JM, et al. Curr Opin Virol. 2019 Apr;35:27-34. doi: 10.1016/j.coviro.2019.02.008. Epub 2019 Mar 12. Curr Opin Virol. 2019. PMID: 30875640 Free PMC article. Review. - Hepatitis C virus NS2 protein contributes to virus particle assembly via opposing epistatic interactions with the E1-E2 glycoprotein and NS3-NS4A enzyme complexes.
Phan T, Beran RK, Peters C, Lorenz IC, Lindenbach BD. Phan T, et al. J Virol. 2009 Sep;83(17):8379-95. doi: 10.1128/JVI.00891-09. Epub 2009 Jun 10. J Virol. 2009. PMID: 19515772 Free PMC article. - Viral protease inhibitors.
Anderson J, Schiffer C, Lee SK, Swanstrom R. Anderson J, et al. Handb Exp Pharmacol. 2009;189(189):85-110. doi: 10.1007/978-3-540-79086-0_4. Handb Exp Pharmacol. 2009. PMID: 19048198 Free PMC article. Review. - Nuclear localization of the NS3 protein of hepatitis C virus and factors affecting the localization.
Muramatsu S, Ishido S, Fujita T, Itoh M, Hotta H. Muramatsu S, et al. J Virol. 1997 Jul;71(7):4954-61. doi: 10.1128/JVI.71.7.4954-4961.1997. J Virol. 1997. PMID: 9188558 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical