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. 2016 Aug 9;17(8):1297.
doi: 10.3390/ijms17081297.

How the Proximal Pocket May Influence the Enantiospecificities of Chloroperoxidase-Catalyzed Epoxidations of Olefins

Alexander N Morozov  1 , David C Chatfield  2
Affiliations

How the Proximal Pocket May Influence the Enantiospecificities of Chloroperoxidase-Catalyzed Epoxidations of Olefins

Alexander N Morozov et al. Int J Mol Sci. .

Abstract

Chloroperoxidase-catalyzed enantiospecific epoxidations of olefins are of significant biotechnological interest. Typical enantiomeric excesses are in the range of 66%-97% and translate into free energy differences on the order of 1 kcal/mol. These differences are generally attributed to the effect of the distal pocket. In this paper, we show that the influence of the proximal pocket on the electron transfer mechanism in the rate-limiting event may be just as significant for a quantitatively accurate account of the experimentally-measured enantiospecificities.

Keywords: Compound I; catalytic reactivity; chloroperoxidase; cytochrome P450; density functional theory; epoxidation; helix dipole; heme-thiolate enzymes; hydrogen bonding; proximal pocket.

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Figures

Figure 1
Figure 1
Proximal pockets of CPO and P450cam.
Figure 2
Figure 2
Bare-thiolate, CPO-I-A (a); and CPO-like, CPO-I-B (b) proximal pocket models of CPO-I.
Figure 3
Figure 3
The UB3LYP/B1//B0 potential energy surfaces (in kcal/mol) connecting the reactant states R and the rate-limiting transition states TS leading to the formation of a Cβ–O bond on the doublet potential energy surfaces for epoxidation of cis-β-methylstyrene (CBMS) by CPO-I-A to give 1R2S and 1S2R products.
Figure 4
Figure 4
The UB3LYP/B1//B0 potential energy surfaces (in kcal/mol) connecting the reactant states R and the rate-limiting transition states TS leading to the formation of a Cβ–O bond on the doublet potential energy surfaces for 1R2S and 1S2R epoxidation of CBMS by CPO-I-B.
Figure 5
Figure 5
Oxyferryl π* attack on C=C bond for model CPO-I-A: (a) LUMO in β manifold of 1R2S TS; (b) LUMO in β manifold of 1S2R TS.
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References

    1. Poulos T.L. Heme enzyme structure and function. Chem. Rev. 2014;114:3919–3962. doi: 10.1021/cr400415k. - DOI - PMC - PubMed
    1. Shaw P.D., Hager L.P. Biological chlorination. IV. Peroxidative nature of enzymatic chlorination. J. Am. Chem. Soc. 1959;81:1011–1012. doi: 10.1021/ja01513a069. - DOI
    1. Shaw P.D., Hager L.P. Biological Chlorination. J. Biol. Chem. 1961;236:1626–1630.
    1. Hager L.P., Morris D.R., Brown F.S., Eberwein H. Chloroperoxidase II: Utilization of halogen ions. J. Biol. Chem. 1966;241:1769–1777. - PubMed
    1. Hofrichter M., Ullrich R. Heme-thiolate haloperoxidases: Versatile biocatalysts with biotechnological and environmental significance. Appl. Microbiol. Biotechnol. 2006;71:276–288. doi: 10.1007/s00253-006-0417-3. - DOI - PubMed