Structure of the human cytomegalovirus protease catalytic domain reveals a novel serine protease fold and catalytic triad

Cell. 1996 Sep 6;86(5):835-43. doi: 10.1016/s0092-8674(00)80157-9.


Proteolytic processing of capsid assembly protein precursors by herpesvirus proteases is essential for virion maturation. A 2.5 A crystal structure of the human cytomegalovirus protease catalytic domain has been determined by X-ray diffraction. The structure defines a new class of serine protease with respect to global-fold topology and has a catalytic triad consisting of Ser-132, His-63, and His-157 in contrast with the Ser-His-Asp triads found in other serine proteases. However, catalytic machinery for activating the serine nucleophile and stabilizing a tetrahedral transition state is oriented similarly to that for members of the trypsin-like and subtilisin-like serine protease families. Formation of the active dimer is mediated primarily by burying a helix of one protomer into a deep cleft in the protein surface of the other.

MeSH terms

  • Amino Acid Sequence
  • Binding Sites
  • Catalysis
  • Cytomegalovirus / enzymology*
  • Endopeptidases / chemistry*
  • Humans
  • Models, Molecular
  • Molecular Sequence Data
  • Protein Conformation*
  • Protein Folding
  • Recombinant Fusion Proteins / chemistry
  • Sequence Alignment
  • Serine Endopeptidases / chemistry*
  • X-Ray Diffraction


  • Recombinant Fusion Proteins
  • Endopeptidases
  • Serine Endopeptidases
  • assemblin