PDBsum entry: 1bt7

Hydrolase

PDB id: 1bt7

Contents

Protein chain

165 a.a.

Metals

_ZN

PDB id:

1bt7

Name:

Hydrolase

Title:

The solution nmr structure of the n-terminal protease domain of the hepatitis c virus (hcv) ns3-protein, from bk strain, 20 structures

Structure:

Ns3 serine protease. Chain: a. Engineered: yes. Mutation: yes. Other_details: compound engineered adding a solubilising tail at thE C-terminus

Source:

Hepatitis c virus. Organism_taxid: 11103. Strain: bk. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.

NMR struc:

20 models

Authors:

G.Barbato,D.O.Cicero,M.C.Nardi,C.Steinkuhler,R.Cortese,R.De Francesco,R.Bazzo

Key ref:

G.Barbato et al. (1999). The solution structure of the N-terminal proteinase domain of the hepatitis C virus (HCV) NS3 protein provides new insights into its activation and catalytic mechanism. J Mol Biol, 289, 371-384. PubMed id: 10366511 DOI: 10.1006/jmbi.1999.2745

Date:

01-Sep-98 Release date: 22-Jun-99

Protein chain

P26663  (POLG_HCVBK) -  Genome polyprotein

Seq: 3010 a.a.

Struc: 165 a.a.*

* PDB and UniProt seqs differ at 10 residue positions (black crosses)

Enzyme reactions

• Enzyme class 1: E.C.2.7.7.48 - RNA-directed Rna polymerase.
• Reaction: Nucleoside triphosphate + RNA(n) = diphosphate + RNA(n+1)
• Enzyme class 2: E.C.3.4.21.98 - Hepacivirin.
• Reaction: Hydrolysis of four peptide bonds in the viral precursor polyprotein, commonly with Asp or Glu in the P6 position, Cys or Thr in P1 and Ser or Ala in P1'.
• Enzyme class 3: E.C.3.6.1.15 - Nucleoside-triphosphatase.
• Reaction: NTP + H₂O = NDP + phosphate
• Enzyme class 4: E.C.3.6.4.13 - Rna helicase.
• Reaction: ATP + H₂O = ADP + phosphate

Note, where more than one E.C. class is given (as above), each may correspond to a different protein domain or, in the case of polyprotein precursors, to a different mature protein.

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

 Gene Ontology (GO) functional annotation 

• Biological process: transformation of host cell by virus (2 terms)
• Biochemical function: catalytic activity (2 terms)

reference

DOI no: 10.1006/jmbi.1999.2745

J Mol Biol 289:371-384 (1999)

PubMed id: 10366511

The solution structure of the N-terminal proteinase domain of the hepatitis C virus (HCV) NS3 protein provides new insights into its activation and catalytic mechanism.

G.Barbato, D.O.Cicero, M.C.Nardi, C.Steinkühler, R.Cortese, R.De Francesco, R.Bazzo.

ABSTRACT

The solution structure of the hepatitis C virus (BK strain) NS3 protein N-terminal domain (186 residues) has been solved by NMR spectroscopy. The protein is a serine protease with a chymotrypsin-type fold, and is involved in the maturation of the viral polyprotein. Despite the knowledge that its activity is enhanced by the action of a viral protein cofactor, NS4A, the mechanism of activation is not yet clear. The analysis of the folding in solution and the differences from the crystallographic structures allow the formulation of a model in which, in addition to the NS4A cofactor, the substrate plays an important role in the activation of the catalytic mechanism. A unique structural feature is the presence of a zinc-binding site exposed on the surface, subject to a slow conformational exchange process.

Selected figure(s)

Figure 2.
Figure 2. A stereoview of the 20 minimum-energy structures is shown. For the overlay, the SCR residues identifying the β-strands plus the helicoidal segments were used. Due to its peculiar mobility, see the NS4a interaction section, strand D1 was omitted in the calculation of the r.m.s.d. The first 21 residues were not included in the structure calculation, because for them no structural information was available.

Figure 7.
Figure 7. Zoomed view of the substrate interaction region. The S′ and S regions range approximately from strand A1 (identified by the position of T38) to loop E2-F2 (G162), encompassing the rather flat surface defined by the E2 strand (F154 bottom of recognition pocket, A157 H-bond candidate with substrate P3 partner) on one side and the α2 helix (oxyanion hole G137-S139; L135 delimiting the top side of the recognition pocket) on the other side.

The above figures are reprinted by permission from Elsevier: J Mol Biol (1999, 289, 371-384) copyright 1999.

Figures were selected by an automated process.