1HAV

HEPATITIS A VIRUS 3C PROTEINASE

Summary for 1HAV

• Entry DOI: 10.2210/pdb1hav/pdb
• Descriptor: HEPATITIS A VIRUS 3C PROTEINASE, CHLORIDE ION, ... (4 entities in total)
• Functional Keywords: polyprotein, coat protein, core protein, rna-directed rna polymerase, hydrolase, thiol protease
• Biological source: Hepatitis A virus; More
• Cellular location: Protein VP2: Virion. Protein VP3: Virion. Protein VP1: Virion. Protein VP1-2A: Virion. Protein 2B: Host cytoplasmic vesicle membrane; Peripheral membrane protein; Cytoplasmic side (Potential). Protein 2C: Host cytoplasmic vesicle membrane; Peripheral membrane protein; Cytoplasmic side (Potential). Protein 3ABC: Host cytoplasmic vesicle membrane; Peripheral membrane protein; Cytoplasmic side (Potential). Protein 3AB: Host cytoplasmic vesicle membrane; Peripheral membrane protein; Cytoplasmic side (Potential). Protein 3A: Host cytoplasmic vesicle membrane; Peripheral membrane protein; Cytoplasmic side (Potential). Protein 3B: Virion (Potential). Picornain 3C: Host cytoplasm (Potential). RNA-directed RNA polymerase 3D-POL: Host cytoplasmic vesicle membrane; Peripheral membrane protein; Cytoplasmic side (Potential): P08617 P08617
• Total number of polymer chains: 2
• Total formula weight: 47892.58

Authors

Bergmann, E.M.,James, M.N.G. (deposition date: 1996-10-23, release date: 1996-12-23, Last modification date: 2024-04-03)

Primary citation

Bergmann, E.M.,Mosimann, S.C.,Chernaia, M.M.,Malcolm, B.A.,James, M.N.
The refined crystal structure of the 3C gene product from hepatitis A virus: specific proteinase activity and RNA recognition.
J.Virol., 71:2436-2448, 1997

PubMed Abstract: The virally encoded 3C proteinases of picornaviruses process the polyprotein produced by the translation of polycistronic viral mRNA. The X-ray crystallographic structure of a catalytically active mutant of the hepatitis A virus (HAV) 3C proteinase (C24S) has been determined. Crystals of this mutant of HAV 3C are triclinic with unit cell dimensions a = 53.6 A, b = 53.5 A, c = 53.2 A, alpha = 99.1 degrees, beta = 129.0 degrees, and gamma = 103.3 degrees. There are two molecules of HAV 3C in the unit cell of this crystal form. The structure has been refined to an R factor of 0.211 (Rfree = 0.265) at 2.0-A resolution. Both molecules fold into the characteristic two-domain structure of the chymotrypsin-like serine proteinases. The active-site and substrate-binding regions are located in a surface groove between the two beta-barrel domains. The catalytic Cys 172 S(gamma) and His 44 N(epsilon2) are separated by 3.9 A; the oxyanion hole adopts the same conformation as that seen in the serine proteinases. The side chain of Asp 84, the residue expected to form the third member of the catalytic triad, is pointed away from the side chain of His 44 and is locked in an ion pair interaction with the epsilon-amino group of Lys 202. A water molecule is hydrogen bonded to His 44 N(delta1). The side-chain phenolic hydroxyl group of Tyr 143 is close to this water and to His 44 N(delta1) and may be negatively charged. The glutamine specificity for P1 residues of substrate cleavage sites is attributed to the presence of a highly conserved His 191 in the S1 pocket. A very unusual environment of two water molecules and a buried glutamate contribute to the imidazole tautomer believed to be important in the P1 specificity. HAV 3C proteinase has the conserved RNA recognition sequence KFRDI located in the interdomain connection loop on the side of the molecule diametrically opposite the proteolytic site. This segment of polypeptide is located between the N- and C-terminal helices, and its conformation results in the formation of a well-defined surface with a strongly charged electrostatic potential. Presumably, this surface of HAV 3C participates in the recognition of the 5' and 3' nontranslated regions of the RNA genome during viral replication.

PubMed: 9032381

Experimental method

X-RAY DIFFRACTION (2 Å)