title: Automated docking to explore subsite binding by glycoside hydrolase family 6 cellobiohydrolases and endoglucanases.
abstract: 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 beta-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 beta-glucosyl residues to the (2)S(O) conformation by binding in subsite -1 adds approximately 7 kcal/mol to substrate intramolecular energies.
authors.affiliation: Department of Chemical and Biological Engineering, Iowa State University, Ames, IA 50011, USA.
authors.forename: Blake
authors.initials: B
authors.lastname: Mertz
authors.forename: Anthony D
authors.initials: AD
authors.lastname: Hill
authors.forename: Chandrika
authors.initials: C
authors.lastname: Mulakala
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Reilly
mesh_terms: D001665:Binding Sites; D002480:Cellulase / Q000737:chemistry*; D043366:Cellulose 1,4-beta-Cellobiosidase / Q000737:chemistry*; D003198:Computer Simulation; D005656:Fungal Proteins / Q000737:chemistry*; D006026:Glycoside Hydrolases / Q000737:chemistry*; D035901:Hypocrea / Q000201:enzymology*; D009844:Oligosaccharides / Q000737:chemistry; D011487:Protein Conformation; D012984:Software; D013816:Thermodynamics
chemical_list: D005656:Fungal Proteins; D009844:Oligosaccharides; D006026:Glycoside Hydrolases; D002480:Cellulase; D043366:Cellulose 1,4-beta-Cellobiosidase