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Human rhinovirus 3C protease: a cysteine protease showing the trypsin(ogen)‐like fold
Author(s) -
Bolognesi Martino,
Spallarossa Andrea,
Ascenzi Paolo
Publication year - 2001
Publication title -
biochemistry and molecular biology education
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.34
H-Index - 39
eISSN - 1539-3429
pISSN - 1470-8175
DOI - 10.1111/j.1539-3429.2001.tb00111.x
Subject(s) - proteases , protease , rhinovirus , trypsin , biochemistry , catalytic triad , cysteine , cysteine protease , papain , masp1 , serine protease , chemistry , oxyanion hole , serine , biology , microbiology and biotechnology , enzyme , virology , virus
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 Gin — Gly peptide bonds or, less commonly, the Gin — Ser, Gin —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. © 2001 IUBMB. Published by Elsevier Science Ltd. All rights reserved.