Structural basis for ligand binding and processivity in cellobiohydrolase Cel6A from Humicola insolens

A Varrot, TP Frandsen, Ingemar von Ossowski, John Boyer, S Cottaz, H Driguez, M Schulein, GJ Davies*

*Corresponding author for this work

Research output: Contribution to journalArticleScientificpeer-review

Abstract

The enzymatic digestion of cellulose entails intimate involvement of cellobiohydrolases, whose characteristic active-center tunnel contributes to a processive degradation of the polysaccharide. The cellobiohydrolase Cel6A displays an active site within a tunnel formed by two extended loops, which are known to open and close in response to ligand binding. Here we present five structures of wild-type and mutant forms of Cel6A from Humicola insolens in complex with nonhydrolyzable thio-oligosaccharides, at resolutions from 1.7-1.1 Angstrom, dissecting the structural accommodation of a processing substrate chain through the active center during hydrolysis. Movement of ligand is facilitated by extensive solvent-mediated interactions and through flexibility in the hydrophobic surfaces provided by a sheath of tryptophan residues.

Original languageEnglish
Pages (from-to)855-864
Number of pages10
JournalSTRUCTURE
Volume11
Issue number7
DOIs
Publication statusPublished - Jul 2003
MoE publication typeA1 Journal article-refereed

Keywords

  • TRICHODERMA-REESEI
  • ACTIVE-SITE
  • 3-DIMENSIONAL STRUCTURE
  • ASPERGILLUS-NIGER
  • CRYSTAL-STRUCTURE
  • CELLULASE
  • COMPLEX
  • REFINEMENT
  • MECHANISMS
  • INHIBITORS

Cite this

Varrot, A., Frandsen, TP., von Ossowski, I., Boyer, J., Cottaz, S., Driguez, H., Schulein, M., & Davies, GJ. (2003). Structural basis for ligand binding and processivity in cellobiohydrolase Cel6A from Humicola insolens. STRUCTURE, 11(7), 855-864. https://doi.org/10.1016/S0969-2126(03)00124-2