Structure and mechanism of endo/exocellulase E4 from Thermomonospora fusca

Nat Struct Biol. 1997 Oct;4(10):810-8. doi: 10.1038/nsb1097-810.


Cellulase E4 from Thermomonospora fusca is unusual in that it has characteristics of both exo- and endo-cellulases. Here we report the crystal structure of a 68K M(r) fragment of E4 (E4-68) at 1.9 A resolution. E4-68 contains both a family 9 catalytic domain, exhibiting an (alpha/alpha)6 barrel fold, and a family III cellulose binding domain, having an antiparallel beta-sandwich fold. While neither of these folds is novel, E4-68 provides the first cellulase structure having interacting catalytic and cellulose binding domains. The complexes of E4-68 with cellopentaose, cellotriose and cellobiose reveal conformational changes associated with ligand binding and allow us to propose a catalytic mechanism for family 9 enzymes. We also provide evidence that E4 has two novel characteristics: first it combines exo- and endo-activities and second, when it functions as an exo-cellulase, it cleaves off cellotetraose units.

Publication types

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

MeSH terms

  • Actinomycetales / enzymology*
  • Amino Acid Sequence
  • Binding Sites
  • Cellulase / chemistry*
  • Cellulase / metabolism*
  • Cellulose / metabolism
  • Cloning, Molecular
  • Conserved Sequence
  • Crystallography, X-Ray
  • Models, Molecular
  • Models, Structural
  • Peptide Fragments / chemistry
  • Peptide Fragments / metabolism
  • Protein Structure, Secondary*
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / metabolism
  • Streptomyces


  • Peptide Fragments
  • Recombinant Proteins
  • Cellulose
  • Cellulase