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Computational study of a model system of enzyme-mediated [4+2] cycloaddition reaction.

Gordeev EG, Ananikov VP - PLoS ONE (2015)

Bottom Line: A possible mechanistic pathway related to an enzyme-catalyzed [4+2] cycloaddition reaction was studied by theoretical calculations at density functional (B3LYP, O3LYP, M062X) and semiempirical levels (PM6-DH2, PM6) performed on a model system.The calculations were carried out for the key [4+2] cycloaddition step considering enzyme-catalyzed biosynthesis of Spinosyn A in a model reaction, where a reliable example of a biological Diels-Alder reaction was reported experimentally.Modeling of such a system with coordination of three amino acids indicated a reliable decrease of activation energy by ~18.0 kcal/mol as compared to a non-catalytic transformation.

View Article: PubMed Central - PubMed

Affiliation: Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Leninsky Prospekt 47, Moscow, Russia.

ABSTRACT
A possible mechanistic pathway related to an enzyme-catalyzed [4+2] cycloaddition reaction was studied by theoretical calculations at density functional (B3LYP, O3LYP, M062X) and semiempirical levels (PM6-DH2, PM6) performed on a model system. The calculations were carried out for the key [4+2] cycloaddition step considering enzyme-catalyzed biosynthesis of Spinosyn A in a model reaction, where a reliable example of a biological Diels-Alder reaction was reported experimentally. In the present study it was demonstrated that the [4+2] cycloaddition reaction may benefit from moving along the energetically balanced reaction coordinate, which enabled the catalytic rate enhancement of the [4+2] cycloaddition pathway involving a single transition state. Modeling of such a system with coordination of three amino acids indicated a reliable decrease of activation energy by ~18.0 kcal/mol as compared to a non-catalytic transformation.

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Optimized molecular structure of transition state VIII-TS.
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pone.0119984.g004: Optimized molecular structure of transition state VIII-TS.

Mentions: Starting with VII as an initial structure, the cycloaddition reaction took place easily through the transition state VIII-TS (Fig. 4) and involved overcoming a small calculated activation barrier of 6.3 kcal/mol (Fig. 3). As expected, the cycloaddition reaction is exothermic due to formation of C-C bonds and due to release of internal strain of the contracted molecule.


Computational study of a model system of enzyme-mediated [4+2] cycloaddition reaction.

Gordeev EG, Ananikov VP - PLoS ONE (2015)

Optimized molecular structure of transition state VIII-TS.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4390235&req=5

pone.0119984.g004: Optimized molecular structure of transition state VIII-TS.
Mentions: Starting with VII as an initial structure, the cycloaddition reaction took place easily through the transition state VIII-TS (Fig. 4) and involved overcoming a small calculated activation barrier of 6.3 kcal/mol (Fig. 3). As expected, the cycloaddition reaction is exothermic due to formation of C-C bonds and due to release of internal strain of the contracted molecule.

Bottom Line: A possible mechanistic pathway related to an enzyme-catalyzed [4+2] cycloaddition reaction was studied by theoretical calculations at density functional (B3LYP, O3LYP, M062X) and semiempirical levels (PM6-DH2, PM6) performed on a model system.The calculations were carried out for the key [4+2] cycloaddition step considering enzyme-catalyzed biosynthesis of Spinosyn A in a model reaction, where a reliable example of a biological Diels-Alder reaction was reported experimentally.Modeling of such a system with coordination of three amino acids indicated a reliable decrease of activation energy by ~18.0 kcal/mol as compared to a non-catalytic transformation.

View Article: PubMed Central - PubMed

Affiliation: Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Leninsky Prospekt 47, Moscow, Russia.

ABSTRACT
A possible mechanistic pathway related to an enzyme-catalyzed [4+2] cycloaddition reaction was studied by theoretical calculations at density functional (B3LYP, O3LYP, M062X) and semiempirical levels (PM6-DH2, PM6) performed on a model system. The calculations were carried out for the key [4+2] cycloaddition step considering enzyme-catalyzed biosynthesis of Spinosyn A in a model reaction, where a reliable example of a biological Diels-Alder reaction was reported experimentally. In the present study it was demonstrated that the [4+2] cycloaddition reaction may benefit from moving along the energetically balanced reaction coordinate, which enabled the catalytic rate enhancement of the [4+2] cycloaddition pathway involving a single transition state. Modeling of such a system with coordination of three amino acids indicated a reliable decrease of activation energy by ~18.0 kcal/mol as compared to a non-catalytic transformation.

Show MeSH
Related in: MedlinePlus