The interactions of peptide inhibitors, obtained by the optimization of N-terminal cleavage products of natural substrates, with the protease of human hepatitis C virus (HCV) are characterized by NMR and modelling studies. The S-binding region of the enzyme and the bound conformation of the ligands are experimentally determined. The NMR data are then used as the experimental basis for modelling studies of the structure of the complex. The S-binding region involves the loop connecting strands E2 and F2, and appears shallow and solvent-exposed. The ligand binds in an extended conformation, forming an antiparallel beta-sheet with strand E2 of the protein, with the P1 carboxylate group in the oxyanion hole.

Cicero, D.o., Barbato, G., Koch, U., Ingallinella, P., Bianchi, E., Nardi, C., et al. (1999). Structural characterization of the interactions of optimized product inhibitors with the N-terminal proteinase domain of the Human Hepatitis C Virus NS3 protein by NMR and Modelling Studies. JOURNAL OF MOLECULAR BIOLOGY, 289, 385-396.

Structural characterization of the interactions of optimized product inhibitors with the N-terminal proteinase domain of the Human Hepatitis C Virus NS3 protein by NMR and Modelling Studies

CICERO, DANIEL OSCAR;
1999-01-01

Abstract

The interactions of peptide inhibitors, obtained by the optimization of N-terminal cleavage products of natural substrates, with the protease of human hepatitis C virus (HCV) are characterized by NMR and modelling studies. The S-binding region of the enzyme and the bound conformation of the ligands are experimentally determined. The NMR data are then used as the experimental basis for modelling studies of the structure of the complex. The S-binding region involves the loop connecting strands E2 and F2, and appears shallow and solvent-exposed. The ligand binds in an extended conformation, forming an antiparallel beta-sheet with strand E2 of the protein, with the P1 carboxylate group in the oxyanion hole.
1999
Pubblicato
Rilevanza internazionale
Articolo
Esperti anonimi
Settore BIO/10 - BIOCHIMICA
English
Cicero, D.o., Barbato, G., Koch, U., Ingallinella, P., Bianchi, E., Nardi, C., et al. (1999). Structural characterization of the interactions of optimized product inhibitors with the N-terminal proteinase domain of the Human Hepatitis C Virus NS3 protein by NMR and Modelling Studies. JOURNAL OF MOLECULAR BIOLOGY, 289, 385-396.
Cicero, Do; Barbato, G; Koch, U; Ingallinella, P; Bianchi, E; Nardi, C; Steinkuhler, C; Cortese, R; Matassa, V; De Francesco, R; Pessi, A; Bazzo, R...espandi
Articolo su rivista
File in questo prodotto:
File Dimensione Formato  
2_1_20.pdf

accesso aperto

Dimensione 375.24 kB
Formato Adobe PDF
375.24 kB Adobe PDF Visualizza/Apri

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/87941
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus 63
  • ???jsp.display-item.citation.isi??? ND
social impact