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PDBsum entry 1qa7
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Hydrolase/hydrolase inhibitor
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PDB id
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1qa7
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Contents |
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* Residue conservation analysis
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References listed in PDB file
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Key reference
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Title
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Crystal structure of an inhibitor complex of the 3c proteinase from hepatitis a virus (hav) and implications for the polyprotein processing in hav.
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Authors
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E.M.Bergmann,
M.M.Cherney,
J.Mckendrick,
S.Frormann,
C.Luo,
B.A.Malcolm,
J.C.Vederas,
M.N.James.
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Ref.
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Virology, 1999,
265,
153-163.
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PubMed id
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Abstract
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The proteolytic processing of the viral polyprotein is an essential step during
the life cycle of hepatitis A virus (HAV), as it is in all positive-sense,
single-stranded RNA viruses of animals. In HAV the 3C proteinase is the only
proteolytic activity involved in the polyprotein processing. The specific
recognition of the cleavage sites by the 3C proteinase depends on the amino acid
sequence of the cleavage site. The structure of the complex of the HAV 3C
proteinase and a dipeptide inhibitor has been determined by X-ray
crystallography. The double-mutant of HAV 3C (C24S, F82A) was inhibited with the
specific inhibitor iodoacetyl-valyl-phenylalanyl-amide. The resulting complex
had an acetyl-Val-Phe-amide group covalently attached to the S(gamma) atom of
the nucleophilic Cys 172 of the enzyme. Crystals of the complex of HAV 3C (C24S,
F82A) acetyl-Val-Phe-amide were found to be monoclinic, space group P2(1),
having 4 molecules in the asymmetric unit and diffracting to 1.9-A resolution.
The final refined structure consists of 4 molecules of HAV 3C (C24S,F82A)
acetyl-Val-Phe-amide, 1 molecule of DMSO, 1 molecule of glycerol, and 514 water
molecules. There are considerable conformational differences among the four
molecules in the asymmetric unit. The final R-factor is 20.4% for all observed
reflections between 15.0- and 1.9-A resolution and the corresponding R(free) is
29.8%. The dipeptide inhibitor is bound to the S(1)(') and S(2)(') specificity
subsites of the proteinase. The crystal structure reveals that the HAV 3C
proteinase possesses a well-defined S(2)(') specificity pocket and suggests that
the P(2)(') residue could be an important determinant for the selection of the
primary cleavage site during the polyprotein processing in HAV.
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Secondary reference #1
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Title
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The refined crystal structure of the 3c gene product from hepatitis a virus: specific proteinase activity and RNA recognition.
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Authors
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E.M.Bergmann,
S.C.Mosimann,
M.M.Chernaia,
B.A.Malcolm,
M.N.James.
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Ref.
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J Virol, 1997,
71,
2436-2448.
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PubMed id
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Secondary reference #2
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Title
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Hepatitis a virus picornain 3c
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Author
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E.M.Bergmann.
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Ref.
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handbook of proteolytic ...
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Secondary reference #3
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Title
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The 3c proteinases of picornaviruses and other positive-Sense, Single-Stranded rna viruses
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Authors
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E.M.Bergmann,
M.N.G.James.
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Ref.
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handbook of exp ...
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Secondary reference #4
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Title
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Expression and characterization of recombinant hepatitis a virus 3c proteinase.
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Authors
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B.A.Malcolm,
S.M.Chin,
D.A.Jewell,
J.R.Stratton-Thomas,
K.B.Thudium,
R.Ralston,
S.Rosenberg.
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Ref.
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Biochemistry, 1992,
31,
3358-3363.
[DOI no: ]
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PubMed id
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