Binding Site Dynamics and Aromatic-Carbohydrate Interactions in Processive and Non-Processive Family 7 Glycoside Hydrolases

Courtney B. Taylor, Christina M. Payne, Michael E. Himmel, Michael F. Crowley, Clare McCabe, Gregg T. Beckham

Research output: Contribution to journalArticlepeer-review

56 Scopus Citations


In nature, processive and non-processive cellulase enzymes deconstruct cellulose to soluble sugars. From structural studies, the consensus is that processive cellulases exhibit tunnels lined with aromatic and polar residues, whereas non-processive cellulases exhibit open clefts with fewer ligand contacts. To gain additional insight into the differences between processive and non-processive cellulases, we examine the glycoside hydrolase family 7 (GH7) cellobiohydrolase, Cel7A, and the endoglucanase, Cel7B, from Trichoderma reesei with molecular simulation. We compare properties related to processivity and compute the binding affinity changes for mutation of four aromatic residues lining the Cel7A active site tunnel and Cel7B cleft to alanine. For the wild-type enzymes, dissimilar behavior is observed at nearly every glucopyranose-binding site from -7 to +2, except in the -2 site, suggesting that the structural differences directly around the catalytic center and at the active site tunnel entrances and exits may all contribute to processivity in GH7s. Interestingly, the -2 site is similar in both enzymes, likely due to the significant conformational change needed in the cellodextrin ligand near this site for catalysis. Moreover, aromatic residue mutations in the Cel7A and Cel7B active sites display only small differences in binding affinity, but the ligand flexibility and enzyme-ligand interactions are only locally affected in Cel7A, whereas the entire ligand is significantly affected when any aromatic residue is mutated in Cel7B.

Original languageAmerican English
Pages (from-to)4924-4933
Number of pages10
JournalJournal of Physical Chemistry B
Issue number17
StatePublished - 2013

NREL Publication Number

  • NREL/JA-5100-57995


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