Molecular modeling and its experimental verification for the catalytic mechanism of Candida antarctica lipase B.
Quantum mechanical and molecular dynamics simulation analysis has been performed on the model system for CALB (Candida antarctica lipase B) with esters to study the reaction mechanism and conformational preference of catalytic hydrolysis and the esterification reaction. Using quantum mechanical analysis, the ping-pong bi-bi mechanism was applied and energies and 3-dimensional binding configurations of the whole reaction pathways were calculated. Further molecular dynamics simulation analysis was performed on the basis of the transition state obtained from quantum mechanical study to observe the effect of structures of,the substrates. Calculation results using substrates of different chain length and chiral configurations were compared for conformational preference. The calculated results showed very small influence on chain length, whereas chiral conformation showed big differences. Calculated results from molecular modeling studies have been compared qualitatively with the experimental data using racemic mixtures of (+/-)-cis-4-acetamido-cyclopent-2-ene-1-ethyl acetate as substrates.
Department of Chemical and Biological Engineering, Korea University, Seoul 136-701, Korea.
Hoon Cheong
HC
Kwon
Dae Young
DY
Shin
Jong Ho
JH
Lee
Seung Wook
SW
Kim
Jeong Won
JW
Kang
D001665:Binding Sites; D002175:Candida / Q000201:enzymology* / Q000235:genetics; D002384:Catalysis; D003198:Computer Simulation; D005656:Fungal Proteins; D006860:Hydrogen Bonding; D006868:Hydrolysis; D008049:Lipase / Q000737:chemistry* / Q000378:metabolism; D008956:Models, Chemical; D008958:Models, Molecular; D011485:Protein Binding; D011487:Protein Conformation; D012984:Software; D013237:Stereoisomerism; D013379:Substrate Specificity; D013816:Thermodynamics
D005656:Fungal Proteins; D008049:Lipase; C431349:lipase B, Candida antarctica