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PMID: 8520469 Published · ppublish English Journal Article Review

The picornaviral 3C proteinases: cysteine nucleophiles in serine proteinase folds.

Protein science : a publication of the Protein Society ·Vol. 4 ·No. 8 ·1995-08-00 ·Pages 1439-45

Malcolm BA

Abstract

The 3C proteinases are a novel group of cysteine proteinases with a serine proteinase-like fold that are responsible for the bulk of polyprotein processing in the Picornaviridae. Because members of this viral family are to blame for several ongoing global pandemic problems (rhinovirus, hepatitis A virus) as well as sporadic outbreaks of more serious pathologies (poliovirus), there has been continuing interest over the last two decades in the development of antiviral therapies. The recent determination of the structure of two of the 3C proteinases by X-ray crystallography opens the door for the application of the latest advances in computer-assisted identification and design of anti-proteinase therapeutic/chemoprophylactic agents.

MeSH Terms
3C Viral Proteases Binding Sites Catalysis Cysteine/chemistry Cysteine Endopeptidases/chemistry,metabolism Picornaviridae/enzymology Protein Folding Serine Endopeptidases/chemistry Substrate Specificity Viral Proteins
Chemicals
Viral Proteins Serine Endopeptidases Cysteine Endopeptidases 3C Viral Proteases 3C proteases Cysteine
Authors & Affiliations
1 authors, click to expand affiliations / ORCID
Malcolm B A
Department of Biochemistry, University of Alberta, Edmonton, Canada.
References (48)
48 references, click to expand
  1. Expression and characterization of recombinant hepatitis A virus 3C proteinase.
    Biochemistry. 1992 Apr 7;31(13):3358-63 PMID: 1313294
  2. A rapid method for determination of endoproteinase substrate specificity: specificity of the 3C proteinase from hepatitis A virus.
    Proc Natl Acad Sci U S A. 1991 Dec 15;88(24):11510-4 PMID: 1662396
  3. Polyprotein processing in cis and in trans by hepatitis A virus 3C protease cloned and expressed in Escherichia coli.
    J Virol. 1992 Sep;66(9):5242-7 PMID: 1323691
  4. Intermolecular cleavage of hepatitis A virus (HAV) precursor protein P1-P2 by recombinant HAV proteinase 3C.
    J Virol. 1992 Nov;66(11):6794-6 PMID: 1328690
  5. Cysteine proteases of positive strand RNA viruses and chymotrypsin-like serine proteases. A distinct protein superfamily with a common structural fold.
    FEBS Lett. 1989 Jan 30;243(2):103-14 PMID: 2645167
  6. Polypeptide 2A of human rhinovirus type 2: identification as a protease and characterization by mutational analysis.
    Virology. 1989 Mar;169(1):68-77 PMID: 2538037
  7. Cleavage of synthetic peptides by purified poliovirus 3C proteinase.
    J Biol Chem. 1989 Jun 15;264(17):9738-41 PMID: 2542331
  8. Chimeric picornavirus polyproteins demonstrate a common 3C proteinase substrate specificity.
    J Virol. 1989 Aug;63(8):3444-52 PMID: 2545915
  9. How do serine proteases really work?
    Biochemistry. 1989 May 2;28(9):3629-37 PMID: 2665806
  10. Detection of a trypsin-like serine protease domain in flaviviruses and pestiviruses.
    Virology. 1989 Aug;171(2):637-9 PMID: 2548336
  11. Hydrolysis of a series of synthetic peptide substrates by the human rhinovirus 14 3C proteinase, cloned and expressed in Escherichia coli.
    J Gen Virol. 1989 Nov;70 ( Pt 11):2931-42 PMID: 2555433
  12. Cleavage of small peptides in vitro by human rhinovirus 14 3C protease expressed in Escherichia coli.
    J Virol. 1989 Dec;63(12):5037-45 PMID: 2555540
  13. A consensus sequence for substrate hydrolysis by rhinovirus 3C proteinase.
    FEBS Lett. 1989 Nov 20;258(1):75-8 PMID: 2556299
  14. A genetic locus in mutant poliovirus genomes involved in overproduction of RNA polymerase and 3C proteinase.
    Virology. 1990 Feb;174(2):504-14 PMID: 2154885
  15. Site-directed mutagenesis suggests close functional relationship between a human rhinovirus 3C cysteine protease and cellular trypsin-like serine proteases.
    J Biol Chem. 1990 May 5;265(13):7180-7 PMID: 2158990
  16. Substrate requirements of human rhinovirus 3C protease for peptide cleavage in vitro.
    J Biol Chem. 1990 Jun 5;265(16):9062-5 PMID: 2160953
  17. Structure-based inhibitor design by using protein models for the development of antiparasitic agents.
    Proc Natl Acad Sci U S A. 1993 Apr 15;90(8):3583-7 PMID: 8475107
  18. Expression of virus-encoded proteinases: functional and structural similarities with cellular enzymes.
    Microbiol Rev. 1993 Dec;57(4):781-822 PMID: 8302216
  19. Structure of human rhinovirus 3C protease reveals a trypsin-like polypeptide fold, RNA-binding site, and means for cleaving precursor polyprotein.
    Cell. 1994 Jun 3;77(5):761-71 PMID: 7515772
  20. Anti-malarial drug development using models of enzyme structure.
    Chem Biol. 1994 Sep;1(1):31-7 PMID: 9383368
  21. On the size of the active site in proteases. I. Papain.
    Biochem Biophys Res Commun. 1967 Apr 20;27(2):157-62 PMID: 6035483
  22. Role of a buried acid group in the mechanism of action of chymotrypsin.
    Nature. 1969 Jan 25;221(5178):337-40 PMID: 5764436
  23. Binding of chloromethyl ketone substrate analogues to crystalline papain.
    Biochemistry. 1976 AUG 24;15(17):3731-8 PMID: 952885
  24. Poliovirus-encoded proteinase 3C: a possible evolutionary link between cellular serine and cysteine proteinase families.
    FEBS Lett. 1986 Jan 6;194(2):253-7 PMID: 3000829
  25. A second virus-encoded proteinase involved in proteolytic processing of poliovirus polyprotein.
    Cell. 1986 Jun 6;45(5):761-70 PMID: 3011278
  26. Expression and site-specific mutagenesis of the poliovirus 3C protease in Escherichia coli.
    Proc Natl Acad Sci U S A. 1986 Aug;83(15):5392-6 PMID: 3016701
  27. In vitro molecular genetics as a tool for determining the differential cleavage specificities of the poliovirus 3C proteinase.
    Nucleic Acids Res. 1987 Mar 11;15(5):2069-88 PMID: 3031587
  28. Site-directed mutagenesis of proteinase 3C results in a poliovirus deficient in synthesis of viral RNA polymerase.
    J Virol. 1987 Jul;61(7):2162-70 PMID: 3035216
  29. Crystal and molecular structures of the complex of alpha-chymotrypsin with its inhibitor turkey ovomucoid third domain at 1.8 A resolution.
    J Mol Biol. 1987 May 20;195(2):397-418 PMID: 3477645
  30. Poliovirus protein 3CD is the active protease for processing of the precursor protein P1 in vitro.
    J Gen Virol. 1988 Jul;69 ( Pt 7):1627-36 PMID: 2839599
  31. Processing and assembly of foot-and-mouth disease virus proteins using subgenomic RNA.
    J Gen Virol. 1988 Sep;69 ( Pt 9):2313-25 PMID: 2842438
  32. Protein 3CD is the major poliovirus proteinase responsible for cleavage of the P1 capsid precursor.
    Virology. 1988 Sep;166(1):265-70 PMID: 2842953
  33. Viral proteinases.
    Annu Rev Biochem. 1988;57:701-54 PMID: 3052288
  34. Viral cysteine proteases are homologous to the trypsin-like family of serine proteases: structural and functional implications.
    Proc Natl Acad Sci U S A. 1988 Nov;85(21):7872-6 PMID: 3186696
  35. Proteolytic cleavage of encephalomyocarditis virus capsid region substrates by precursors to the 3C enzyme.
    J Virol. 1989 Mar;63(3):1054-8 PMID: 2536819
  36. Proteolytic processing of picornaviral polyprotein.
    Annu Rev Microbiol. 1990;44:603-23 PMID: 2252396
  37. Cleavage specificity of the poliovirus 3C protease is not restricted to Gln-Gly at the 3C/3D junction.
    J Gen Virol. 1990 Nov;71 ( Pt 11):2553-63 PMID: 2174954
  38. Coinfection with recombinant vaccinia viruses expressing poliovirus P1 and P3 proteins results in polyprotein processing and formation of empty capsid structures.
    J Virol. 1991 Apr;65(4):2088-92 PMID: 1848318
  39. Site-directed mutagenesis of the putative catalytic triad of poliovirus 3C proteinase.
    J Biol Chem. 1991 Mar 25;266(9):5412-6 PMID: 1848550
  40. Analysis of putative active site residues of the poliovirus 3C protease.
    Virology. 1991 Apr;181(2):609-19 PMID: 1849679
  41. Autoproteolytic cleavage of recombinant 3C proteinase of hepatitis A virus.
    Virology. 1991 Jun;182(2):861-4 PMID: 1850933
  42. Specificity of the polioviral proteinase 3C towards genetically engineered cleavage sites in the viral capsid.
    J Gen Virol. 1991 May;72 ( Pt 5):1159-63 PMID: 1851816
  43. Expression of functional beta-galactosidase containing the coxsackievirus 3C protease as an internal fusion.
    Biochem Biophys Res Commun. 1991 May 31;177(1):243-51 PMID: 1904218
  44. Proteinase trapping: screening for viral proteinase mutants by alpha complementation.
    Proc Natl Acad Sci U S A. 1991 Jul 15;88(14):5979-83 PMID: 1648726
  45. Biologically active protease 3C of human rhinovirus 1A is expressed from a cloned cDNA segment in Escherichia coli.
    Virology. 1991 Oct;184(2):587-94 PMID: 1653490
  46. Role for the P4 amino acid residue in substrate utilization by the poliovirus 3CD proteinase.
    J Virol. 1991 Nov;65(11):6111-23 PMID: 1656088
  47. Protein folding and association: insights from the interfacial and thermodynamic properties of hydrocarbons.
    Proteins. 1991;11(4):281-96 PMID: 1758883
  48. A genetic system for studying the activity of a proteolytic enzyme.
    Proc Natl Acad Sci U S A. 1992 May 1;89(9):4159-62 PMID: 1570342
Article Info
Journal
Protein science : a publication of the Protein Society
Abbr.
Protein Sci
ISSN
0961-8368
DOI
10.1002/pro.5560040801
Published
1995-08-00
Pages
1439-45
Language
English
Region
United States
NLM ID
9211750
PMCID
PMC2143194
Subset
IM
External Links
PubMed source DOI: 10.1002/pro.5560040801 PMC Full Text View journal details
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