Automated docking to explore subsite binding by glycoside hydrolase family 6 cellobiohydrolases and endoglucanases

• Published in: Biopolymers Vol. 87; no. 4; pp. 249 - 260
• Main Authors: Mertz, Blake, Hill, Anthony D., Mulakala, Chandrika, Reilly, Peter J.
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 01.11.2007
• Subjects: AutoDock; automated docking; Binding Sites; cellobiohydrolase; Cellulase - chemistry; Cellulose 1,4-beta-Cellobiosidase - chemistry; Computer Simulation; endoglucanase; Fungal Proteins - chemistry; glycoside hydrolase Family 6; Glycoside Hydrolases - chemistry; Hypocrea - enzymology; Hypocrea jecorina; Oligosaccharides - chemistry; Protein Conformation; Software; Thermobifida fusca; Thermodynamics; Trichoderma reesei
• ISSN: 0006-3525; 1097-0282
• DOI: 10.1002/bip.20831

Cellooligosaccharides were computationally docked using AutoDock into the active sites of the glycoside hydrolase Family 6 enzymes Hypocrea jecorina (formerly Trichoderma reesei) cellobiohydrolase and Thermobifida fusca endoglucanase. Subsite –2 exerts the greatest intermolecular energy in binding β‐glucosyl residues, with energies progressively decreasing to either side. Cumulative forces imparting processivity exerted by these two enzymes are significantly less than by the equivalent glycoside hydrolase Family 7 enzymes studied previously. Putative subsites –4, –3, +3, and +4 exist in H. jecorina cellobiohydrolase, along with putative subsites –4, –3, and +3 in T. fusca endoglucanase, but they are less important than subsites –2, –1, +1, and +2. In general, binding adds 3–7 kcal/mol to ligand intramolecular energies because of twisting of scissile glycosidic bonds. Distortion of β‐glucosyl residues to the 2SO conformation by binding in subsite –1 adds ∼7 kcal/mol to substrate intramolecular energies. © 2007 Wiley Periodicals, Inc. Biopolymers 87: 249–260, 2007. This article was originally published online as an accepted preprint. The “Published Online” date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com