Dataset Information

Global and Kinetic Profiles of Substrate Diffusion in Candida antarctica Lipase B: Molecular Dynamics with the Markov-State Model.

ABSTRACT: Profiling substrate diffusion pathways with kinetic information, which accounts for the dynamic nature of enzyme-substrate interaction, can enable molecular reengineering of enzymes and process optimization of enzymatic catalysis. Candida antarctica lipase B (CALB) is extensively used for producing various chemicals because of its rich catalytic mechanisms, broad substrate spectrum, thermal stability, and tolerance to organic solvents. In this study, an all-atom molecular dynamics (MD) combined with Markov-state models (MSMs) implemented in pyEMMA was proposed to simulate diffusion pathways of 4-nitrophenyl ester (4NPE), a commonly used substrate, from the surface into the active site of CALB. Six important metastable conformations of CALB were identified in the diffusion process, including a closed state. An induced-fit mechanism incorporating multiple pathways with molecular information was proposed, which might find unprecedented applications for the rational design of lipase for green catalysis.

SUBMITTER: Lu C

PROVIDER: S-EPMC7203684 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

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Publications

Global and Kinetic Profiles of Substrate Diffusion in <i>Candida antarctica</i> Lipase B: Molecular Dynamics with the Markov-State Model.

Lu Chenlin C Peng Xue X Lu Diannan D Liu Zheng Z

ACS omega 20200423 17

Profiling substrate diffusion pathways with kinetic information, which accounts for the dynamic nature of enzyme-substrate interaction, can enable molecular reengineering of enzymes and process optimization of enzymatic catalysis. <i>Candida antarctica</i> lipase B (CALB) is extensively used for producing various chemicals because of its rich catalytic mechanisms, broad substrate spectrum, thermal stability, and tolerance to organic solvents. In this study, an all-atom molecular dynamics (MD) co ...[more]

PMID: 32391467

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Project description:BackgroundThe Lipase Engineering Database (LED) integrates information on sequence, structure and function of lipases, esterases and related proteins with the alpha/beta hydrolase fold. A new superfamily for Candida antarctica lipase A (CALA) was introduced including the recently published crystal structure of CALA. Since CALA has a highly divergent sequence in comparison to other alpha/beta hydrolases, the Lipase Engineering Database was used to classify CALA in the frame of the already established classification system. This involved the comparison of CALA to similar structures as well as sequence-based comparisons against the content of the LED.ResultsThe new release 3.0 (December 2009) of the Lipase Engineering Database contains 24783 sequence entries for 18585 proteins as well as 656 experimentally determined protein structures, including the structure of CALA. In comparison to the previous release 1 with 4322 protein and 167 structure entries this update represents a significant increase in data volume. By comparing CALA to representative structures from all superfamilies, a structure from the deacetylase superfamily was found to be most similar to the structure of CALA. While the alpha/beta hydrolase fold is conserved in both proteins, the major difference is found in the cap region. Sequence alignments between both proteins show a sequence similarity of only 15%. A multisequence alignment of both protein families was used to create hidden Markov models for the cap region of CALA and showed that the cap region of CALA is unique among all other proteins of the alpha/beta hydrolase fold. By specifically comparing the substrate binding pocket of CALA to other binding pockets of alpha/beta hydrolases, the binding pocket of Candida rugosa lipase was identified as being highly similar. This similarity also applied to the lid of Candida rugosa lipase in comparison to the potential lid of CALA.ConclusionThe LED serves as a valuable tool for the systematic analysis of single proteins or protein families. The updated release 3.0 was used for the evaluation of alpha/beta hydrolases. The HTML version of the database with new features is available at http://www.led.uni-stuttgart.de and provides sequences, structures and a set of analysis tools including phylogenetic trees and HMM profiles.

Dataset Information

Global and Kinetic Profiles of Substrate Diffusion in Candida antarctica Lipase B: Molecular Dynamics with the Markov-State Model.

Publications

Global and Kinetic Profiles of Substrate Diffusion in <i>Candida antarctica</i> Lipase B: Molecular Dynamics with the Markov-State Model.

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