Human rhinovirus 3C protease: A cysteine protease showing the trypsin(ogen)-like fold

Martino Bolognesi, Andrea Spallarossa, Paolo Ascenzi

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Viral-encoded proteases cleave precursor polyprotein(s) leading to maturation of infectious virions. Strikingly, human rhinovirus 3C protease shows the trypsin(ogen)-like serine protease fold based on two topologically equivalent six-stranded β-barrels, but displays residue Cys147 as the active site nucleophile. By contrast, papain, which is representative of most cysteine proteases, does not display the trypsin(ogen)-like fold. Remarkably, in human rhinovirus 3C cysteine protease, the catalytic residues Cys147, His40 and Glu71 are positioned as Ser195, His57 and Asp102, respectively, building up the catalytic triad of serine proteases in the chymotrypsin-trypsin-elastase family. However, as compared to trypsin-like serine proteases and their zymogens, residue His40 and the oxyanion hole of human rhinovirus 3C cysteine protease, both key structural components of the active site, are located closer to the protein core. Human rhinovirus 3C cysteine protease cleaves preferentially Gln - Gly peptide bonds or, less commonly, the Gln - Ser, Gln - Ala, Glu - Ser or Glu - Gly pairs. Finally, human rhinovirus 3C cysteine protease and the 3CD cysteine protease-polymerase covalent complex bind the 5′ non-coding region of rhinovirus genomic RNA, an essential function for replication of the viral genome.

Original languageEnglish
Pages (from-to)169-172
Number of pages4
JournalBiochemistry and Molecular Biology Education
Volume29
Issue number4
DOIs
Publication statusPublished - 2001

Fingerprint

Cysteine Proteases
Trypsin
Serine Proteases
glutaminyl-glycine
Catalytic Domain
Polyproteins
Rhinovirus
Nucleophiles
Enzyme Precursors
Papain
Viral Genome
Pancreatic Elastase
Virion
3C proteases
estropipate
Peptide Hydrolases
Genes
RNA
Peptides
Proteins

Keywords

  • Human rhinovirus 3C cysteine protease
  • Trypsin(ogen)-like fold

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology

Cite this

Human rhinovirus 3C protease : A cysteine protease showing the trypsin(ogen)-like fold. / Bolognesi, Martino; Spallarossa, Andrea; Ascenzi, Paolo.

In: Biochemistry and Molecular Biology Education, Vol. 29, No. 4, 2001, p. 169-172.

Research output: Contribution to journalArticle

Bolognesi, Martino ; Spallarossa, Andrea ; Ascenzi, Paolo. / Human rhinovirus 3C protease : A cysteine protease showing the trypsin(ogen)-like fold. In: Biochemistry and Molecular Biology Education. 2001 ; Vol. 29, No. 4. pp. 169-172.
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