title: Investigation of an "alternate water supply system" in enzymatic hydrolysis in the processive endocellulase Cel7A from Rasamsonia emersonii by molecular dynamics simulation.
abstract: Cel7A from Rasamsonia emersonii is one of the processive endocellulases classified under family 7 glycoside hydrolase. Molecular dynamics simulations were carried out to obtain the optimized sliding and hydrolyzing conformations, in which the reducing ends of sugar chains are located on different sites. Hydrogen bonds are investigated to clarify the interactions between protein and substrate in either conformation. Nine hydrogen bonding interactions are identified in the sliding conformation, and six similar interactions are also found correspondingly in the hydrolyzing conformation. In addition, four strong hydrophobic interactions are also determined. The domain cross-correlation map analysis shows movement correlation of protein including autocorrelation between residues. The root mean square fluctuations analysis represents the various flexibilities of different fragment in the two conformations. Comparing the two conformations reveals the water-supply mechanism of selective hydrolysis of cellulose in Cel7A. The mechanism can be described as follow. When the reducing end of substrate slides from the unhydrolyzing site (sliding conformation) to the hydrolyzing site (hydrolyzing conformation), His225 is pushed down and rotated, the rotation leads to the movement of Glu209 with the interstrand hydrogen bonding in β-sheet. It further makes Asp211 close to the hydrolysis center and provides a water molecule bounding on its carboxyl in the previous unhydrolyzing site. After the hydrolysis takes place and the product is excluded from the enzyme, the Asp211 comes back to its initial position. In summary, Asp211 acts as an elevator to transport outer water molecules into the hydrolysis site for every other glycosidic bond.
authors.affiliation: Institute of Theoretical Chemistry, Jilin University, Changchun, 130023, People's Republic of China.
authors.forename: Xun
authors.initials: X
authors.lastname: Sun
authors.affiliation: Institute of Theoretical Chemistry, Jilin University, Changchun, 130023, People's Republic of China.
authors.forename: Meng-Dan
authors.initials: MD
authors.lastname: Qian
authors.affiliation: Key Laboratory for Molecular Enzymology and Engineering of Ministry of Education, National Engineering Laboratory for AIDS Vaccine, College of Life Sciences, Jilin University, Changchun, 130012, People's Republic of China.
authors.forename: Shan-Shan
authors.initials: SS
authors.lastname: Guan
authors.affiliation: Key Laboratory for Molecular Enzymology and Engineering of Ministry of Education, National Engineering Laboratory for AIDS Vaccine, College of Life Sciences, Jilin University, Changchun, 130012, People's Republic of China.
authors.forename: Ya-Ming
authors.initials: YM
authors.lastname: Shan
authors.affiliation: Bethune pharmaceutical factory, Jilin University, Changchun, 130012, People's Republic of China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Dong
authors.affiliation: Institute of Theoretical Chemistry, Jilin University, Changchun, 130023, People's Republic of China.
authors.forename: Hao
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Institute of Theoretical Chemistry, Jilin University, Changchun, 130023, People's Republic of China.
authors.forename: Song
authors.initials: S
authors.lastname: Wang
authors.affiliation: Key Laboratory for Molecular Enzymology and Engineering of Ministry of Education, National Engineering Laboratory for AIDS Vaccine, College of Life Sciences, Jilin University, Changchun, 130012, People's Republic of China.|Department of Computer Science, C.S. Bond Life Sciences Center, University of Missouri Columbia, Missouri, 65211.
authors.forename: Wei-Wei
authors.initials: WW
authors.lastname: Han
mesh_terms: D001203:Ascomycota / Q000201:enzymology*; D001665:Binding Sites; D020134:Catalytic Domain; D044602:Cellulases / Q000737:chemistry / Q000378:metabolism*; D005656:Fungal Proteins / Q000737:chemistry / Q000378:metabolism*; D006860:Hydrogen Bonding; D006868:Hydrolysis; D056004:Molecular Dynamics Simulation; D013816:Thermodynamics; D014867:Water / Q000737:chemistry* / Q000378:metabolism
chemical_list: D005656:Fungal Proteins; D014867:Water; D044602:Cellulases
keywords: Cel7A; MD simulation; celluase; processive hydrolysis; water supply system