Limits...
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.

Show MeSH

Related in: MedlinePlus

Structural decomposition analysis of the cycloaddition reaction.Structural decomposition analysis of the cycloaddition reaction involved in the biosynthesis of Spinosyn A into principal components (the atom numbering was the same as in compound 1 for comparative purpose).
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4390235&req=5

pone.0119984.g002: Structural decomposition analysis of the cycloaddition reaction.Structural decomposition analysis of the cycloaddition reaction involved in the biosynthesis of Spinosyn A into principal components (the atom numbering was the same as in compound 1 for comparative purpose).

Mentions: The classical Diels-Alder reaction involves cycloaddition of butadiene and ethylene units and results in a cyclohexene ring via a single transition state (Fig. 2a) [1, 2, 3, 4, 8, 9, 10, 11, 12]. In the biosynthesis of Spinosyn A, several structural changes were introduced to this [4+2] reaction core, and an important question is to what extent these changes may affect the reactivity of the ring construction. Possible contributions of the following known factors have been considered in the present study: 1) influence of substituents in the substrate; 2) polarization of the substrate; and 3) influence of hydrogen bonding.


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

Gordeev EG, Ananikov VP - PLoS ONE (2015)

Structural decomposition analysis of the cycloaddition reaction.Structural decomposition analysis of the cycloaddition reaction involved in the biosynthesis of Spinosyn A into principal components (the atom numbering was the same as in compound 1 for comparative purpose).
© Copyright Policy
Related In: Results  -  Collection

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

pone.0119984.g002: Structural decomposition analysis of the cycloaddition reaction.Structural decomposition analysis of the cycloaddition reaction involved in the biosynthesis of Spinosyn A into principal components (the atom numbering was the same as in compound 1 for comparative purpose).
Mentions: The classical Diels-Alder reaction involves cycloaddition of butadiene and ethylene units and results in a cyclohexene ring via a single transition state (Fig. 2a) [1, 2, 3, 4, 8, 9, 10, 11, 12]. In the biosynthesis of Spinosyn A, several structural changes were introduced to this [4+2] reaction core, and an important question is to what extent these changes may affect the reactivity of the ring construction. Possible contributions of the following known factors have been considered in the present study: 1) influence of substituents in the substrate; 2) polarization of the substrate; and 3) influence of hydrogen bonding.

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