Dataset Information

Computational Studies of Candida Antarctica Lipase B to Test Its Capability as a Starting Point To Redesign New Diels-Alderases.

ABSTRACT: The design of new biocatalysts is a target that is receiving increasing attention. One of the most popular reactions in this regard is the Diels-Alder cycloaddition because of its applications in organic synthesis and the absence of efficient natural enzymes that catalyze it. In this paper, the possibilities of using the highly promiscuous Candida Antarctica lipase B as a protein scaffold to redesign a Diels-Alderase has been explored by means of theoretical quantum mechanics/molecular mechanics (QM/MM) molecular dynamics simulations. Free energy surfaces have been computed for two reactions in the wild-type and in several mutants with hybrid AM1/MM potentials with corrections at M06-2X/MM level. The study of the counterpart reactions in solution has allowed performing comparative analysis that render interesting conclusions. Since the dienophile anchors very well in the oxyanion hole of all tested protein variants, the slight electronic changes from reactant complex to the transition state suggest that mutations should be focused in favoring the formation of reactive conformations of a reactant complex that, in turn, would reduce the energy barrier.

SUBMITTER: Swiderek K

PROVIDER: S-EPMC4777658 | biostudies-literature | 2016 Mar

REPOSITORIES: biostudies-literature

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Computational Studies of Candida Antarctica Lipase B to Test Its Capability as a Starting Point To Redesign New Diels-Alderases.

Świderek Katarzyna K Moliner Vicent V

The journal of physical chemistry. B 20151215 8

The design of new biocatalysts is a target that is receiving increasing attention. One of the most popular reactions in this regard is the Diels-Alder cycloaddition because of its applications in organic synthesis and the absence of efficient natural enzymes that catalyze it. In this paper, the possibilities of using the highly promiscuous Candida Antarctica lipase B as a protein scaffold to redesign a Diels-Alderase has been explored by means of theoretical quantum mechanics/molecular mechanics ...[more]

PMID: 26624234

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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

Computational Studies of Candida Antarctica Lipase B to Test Its Capability as a Starting Point To Redesign New Diels-Alderases.

Publications

Computational Studies of Candida Antarctica Lipase B to Test Its Capability as a Starting Point To Redesign New Diels-Alderases.

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