title: Molecular dynamics simulation of the processive endocellulase Cel48F from Clostridium cellulolyticum: a novel "water-control mechanism" in enzymatic hydrolysis of cellulose.
abstract: Glycoside hydrolase of Cel48F from Clostridium cellulolyticum is an important processive cellulose, which can hydrolyze cellulose into cellobiose. Molecular dynamics simulations were used to investigate the hydrolysis mechanism of cellulose. The two conformations of the Cel48F-cellotetrose complex in which the cellotetroses are bound at different sites (known as the sliding conformation and the hydrolyzing conformation) were simulated. By comparing these two conformations, a water-control mechanism is proposed, in which the hydrolysis proceeds by providing a water molecule for every other glucosidic linkage. The roles of certain key residues are determined: Glu55 and Asp230 are the most probable candidates for acid and base, respectively, in the mechanism of inverting anomeric carbon. Met414 and Trp417 constitute the water-control system. Glu44 might keep the substrate at a certain location within the active site or help the substrate chain to move from the sliding conformation to the hydrolyzing conformation. The other hydrophobic residues around the substrate can decrease the sliding energy barrier or provide a hydrophobic environment to resist entry of the surrounding water molecules into the active site, except for those coming from a specific water channel.
authors.affiliation: State Key Laboratory of Theoretical and Computational Chemistry, Institute of Theoretical Chemistry, Jilin University, Changchun, 130023, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Zhang
authors.forename: Ji-long
authors.initials: JL
authors.lastname: Zhang
authors.forename: Lu
authors.initials: L
authors.lastname: Sun
authors.forename: Xiao-di
authors.initials: XD
authors.lastname: Niu
authors.forename: Song
authors.initials: S
authors.lastname: Wang
authors.forename: Ya-ming
authors.initials: YM
authors.lastname: Shan
mesh_terms: D001665:Binding Sites; D020134:Catalytic Domain; D002475:Cellobiose / Q000378:metabolism; D044602:Cellulases / Q000737:chemistry* / Q000378:metabolism; D002482:Cellulose / Q000378:metabolism; D046973:Ruminiclostridium cellulolyticum / Q000201:enzymology; D018360:Crystallography, X-Ray; D006860:Hydrogen Bonding; D006868:Hydrolysis; D008968:Molecular Conformation; D056004:Molecular Dynamics Simulation; D013379:Substrate Specificity; D014867:Water / Q000737:chemistry*
chemical_list: D014867:Water; D002475:Cellobiose; D002482:Cellulose; D044602:Cellulases
keywords: Cel48F; MD simulation; cellulase; processive hydrolysis; water-control mechanism