PDBsum entry: 1a1q

Hydrolase

PDB id: 1a1q

Contents

Protein chains

183 a.a.*

170 a.a.*

Metals

_ZN ×3

* C-alpha coords only

PDB id:

1a1q

Name:

Hydrolase

Title:

Hepatitis c virus ns3 proteinase

Structure:

Ns3 proteinase. Chain: a, b, c. Engineered: yes

Source:

Hepatitis c virus. Organism_taxid: 11103. Strain: type 1b. Variant: bk isolate. Gene: cdna. Expressed in: escherichia coli. Expression_system_taxid: 562. Isolated from pat. Other_details: expressed as soluble protein

Resolution:

2.40Å R-factor: 0.225 R-free: 0.320

Authors:

R.A.Love,H.E.Parge,J.A.Wickersham,Z.Hostomsky,N.Habuka, E.W.Moomaw,T.Adachi,Z.Hostomska

Key ref:

R.A.Love et al. (1996). The crystal structure of hepatitis C virus NS3 proteinase reveals a trypsin-like fold and a structural zinc binding site. Cell, 87, 331-342. PubMed id: 8861916 DOI: 10.1016/S0092-8674(00)81350-1

Date:

12-Dec-97 Release date: 25-Mar-98

Protein chains

P26663  (POLG_HCVBK) -  Genome polyprotein

Seq: 3010 a.a.

Struc: 183 a.a.*

Protein chain

P26663  (POLG_HCVBK) -  Genome polyprotein

Seq: 3010 a.a.

Struc: 170 a.a.*

* PDB and UniProt seqs differ at 8 residue positions (black crosses)

Enzyme reactions

• Enzyme class 1: Chains A, B, C: E.C.2.7.7.48 - RNA-directed Rna polymerase.
• Reaction: Nucleoside triphosphate + RNA(n) = diphosphate + RNA(n+1)
• Enzyme class 2: Chains A, B, C: 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: Chains A, B, C: E.C.3.6.1.15 - Nucleoside-triphosphatase.
• Reaction: NTP + H₂O = NDP + phosphate
• Enzyme class 4: Chains A, B, C: 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: 10.1016/S0092-8674(00)81350-1

Cell 87:331-342 (1996)

PubMed id: 8861916

The crystal structure of hepatitis C virus NS3 proteinase reveals a trypsin-like fold and a structural zinc binding site.

R.A.Love, H.E.Parge, J.A.Wickersham, Z.Hostomsky, N.Habuka, E.W.Moomaw, T.Adachi, Z.Hostomska.

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.

Selected figure(s)

Figure 4.
Figure 4. Model of a Bound Polypeptide Substrate Containing the NS3/4A JunctionSide-by-side stereo view of the NS3/4A substrate (color-coded: green, C; red, O; blue, N) modeled into the active site of HCV NS3P, which is covered by a molecular surface in white dots (generated by the MS program[12] using a 1.6 Å probe radius). The Cα trace of NS3P is shown in yellow, with the oxyanion-stabilizing loop in purple and the extended strand βE2 in red. NS3P side chains (color-coded: yellow, C; red, O; blue, N) are shown for residues comprising the S1 specificity pocket (L135, F154, A157), the potential P6 recognition elements (R161, K165), and active-site serine (S139). The substrate is labeled according to the standard P/P' convention, while the HCV residues are labeled in the single-letter amino acid code.

Figure 5.
Figure 5. Solvent-Accessible Surface of NS3P Monomer 1, Colored by Hydrophobicity, Such That Nonpolar Residues Are White, Charged Residues Are Deep Magenta, and Polar Residues Are Medium Shades of MagentaThe central white region is the hydrophobic patch (approximately 400 Å^2) discussed in the text. In the crystal, there are two N-terminal strands from neighboring molecules bound to this patch, namely βC0 from monomer 3 (blue ribbon) and βA0 from monomer 1' (green ribbon). Strand βC0 buries Cys-16 and Ile-18, while strand βA0 buries Ile-3 and Ala-5, into the center of the hydrophobic surface patch. Residues Ser-20 of βC0 and Ser-7 of βA0 lie at the edge of the interface and hydrogen-bond to monomer 1. Also shown in yellow (at bottom horizon of surface) is the P3′ residue of a modeled substrate polypeptide (see Figure 4), included here as a directional reference to the active site.

The above figures are reprinted by permission from Cell Press: Cell (1996, 87, 331-342) copyright 1996.

Figures were selected by an automated process.