Crystal Structure of the Human Adenovirus Proteinase With Its 11 Amino Acid Cofactor

EMBO J. 1996 Apr 15;15(8):1778-83.

Abstract

The three-dimensional structure of the human adenovirus-2 proteinase complexed with its 11 amino acid cofactor, pVIc, was determined at 2.6 A resolution by X-ray crystallographic analysis. The fold of this protein has not been seen before. However, it represents an example of either subtly divergent or powerfully convergent evolution, because the active site contains a Cys-His-Glu triplet and oxyanion hole in an arrangement similar to that in papain. Thus, the adenovirus proteinase represents a new, fifth group of enzymes that contain catalytic triads. pVIc, which extends a beta-sheet in the main chain, is distant from the active site, yet its binding increases the catalytic rate constant 300-fold for substrate hydrolysis. The structure reveals several potential targets for antiviral therapy.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenoviruses, Human / enzymology*
  • Adenoviruses, Human / genetics
  • Amino Acid Sequence
  • Binding Sites / genetics
  • Capsid / chemistry
  • Capsid / genetics
  • Capsid Proteins*
  • Coenzymes / chemistry*
  • Coenzymes / genetics
  • Crystallography, X-Ray
  • Cysteine Endopeptidases / chemistry*
  • Evolution, Molecular
  • Humans
  • Models, Molecular
  • Molecular Sequence Data
  • Molecular Structure
  • Peptide Fragments / chemistry
  • Peptide Fragments / genetics
  • Protein Binding
  • Protein Conformation
  • Protein Structure, Secondary
  • Substrate Specificity
  • Viral Proteins*

Substances

  • Capsid Proteins
  • Coenzymes
  • Peptide Fragments
  • Viral Proteins
  • polypeptide VI, adenovirus
  • Cysteine Endopeptidases
  • L3 23K protein, adenovirus

Associated data

  • PDB/1GJL