1NS3

STRUCTURE OF HCV PROTEASE (BK STRAIN)

Summary for 1NS3

• Entry DOI: 10.2210/pdb1ns3/pdb
• Descriptor: NS3 PROTEASE, NS4A PEPTIDE, ZINC ION, ... (4 entities in total)
• Functional Keywords: hydrolase, serine proteinase, complex (hydrolase-peptide), complex (hydrolase-peptide) complex, complex (hydrolase/peptide)
• Biological source: Hepatitis C virus; More
• Cellular location: Core protein p21: Host endoplasmic reticulum membrane; Single-pass membrane protein. Core protein p19: Virion (By similarity). Envelope glycoprotein E1: Virion membrane; Single-pass type I membrane protein (Potential). Envelope glycoprotein E2: Virion membrane; Single-pass type I membrane protein (Potential). p7: Host endoplasmic reticulum membrane; Multi-pass membrane protein (By similarity). Protease NS2-3: Host endoplasmic reticulum membrane; Multi-pass membrane protein (Potential). Serine protease NS3: Host endoplasmic reticulum membrane; Peripheral membrane protein (By similarity). Non-structural protein 4A: Host endoplasmic reticulum membrane; Single-pass type I membrane protein (Potential). Non-structural protein 4B: Host endoplasmic reticulum membrane; Multi-pass membrane protein (By similarity). Non-structural protein 5A: Host endoplasmic reticulum membrane; Peripheral membrane protein (By similarity). RNA-directed RNA polymerase: Host endoplasmic reticulum membrane; Single-pass type I membrane protein (Potential): P26663 P26663
• Total number of polymer chains: 4
• Total formula weight: 42672.21

Authors

Yan, Y.,Munshi, S.,Chen, Z. (deposition date: 1997-04-05, release date: 1998-04-08, Last modification date: 2024-02-14)

Primary citation

Yan, Y.,Li, Y.,Munshi, S.,Sardana, V.,Cole, J.L.,Sardana, M.,Steinkuehler, C.,Tomei, L.,De Francesco, R.,Kuo, L.C.,Chen, Z.
Complex of NS3 protease and NS4A peptide of BK strain hepatitis C virus: a 2.2 A resolution structure in a hexagonal crystal form.
Protein Sci., 7:837-847, 1998

PubMed Abstract: The crystal structure of the NS3 protease of the hepatitis C virus (BK strain) has been determined in the space group P6(3)22 to a resolution of 2.2 A. This protease is bound with a 14-mer peptide representing the central region of the NS4A protein. There are two molecules of the NS3(1-180)-NS4A(21'-34') complex per asymmetric unit. Each displays a familiar chymotrypsin-like fold that includes two beta-barrel domains and four short alpha-helices. The catalytic triad (Ser-139, His-57, and Asp-81) is located in the crevice between the beta-barrel domains. The NS4A peptide forms an almost completely enclosed peptide surface association with the protease. In contrast to the reported H strain complex of NS3 protease-NS4A peptide in a trigonal crystal form (Kim JL et al., 1996, Cell 87:343-355), the N-terminus of the NS3 protease is well-ordered in both molecules in the asymmetric unit of our hexagonal crystal form. The folding of the N-terminal region of the NS3 protease is due to the formation of a three-helix bundle as a result of crystal packing. When compared with the unbound structure (Love RA et al., 1996, Cell 87:331-342), the binding of the NS4A peptide leads to the ordering of the N-terminal 28 residues of the NS3 protease into a beta-strand and an alpha-helix and also causes local rearrangements important for a catalytically favorable conformation at the active site. Our analysis provides experimental support for the proposal that binding of an NS4A-mimicking peptide, which increases catalytic rates, is necessary but not sufficient for formation of a well-ordered, compact and, hence, highly active protease molecule.

PubMed: 9568891

Experimental method

X-RAY DIFFRACTION (2.8 Å)