Fe(III)-Mimochrome VI (MC6) is a recently reported artificial heme-peptide conjugate system with a high peroxidase-like activity. By design, its structure features a five-coordinated Fe(III)-deuteroporphyrin active site, embedded in a compact α-helix–heme–α-helix “sandwich” motif. Up to now, no detailed MC6 structural characterization is available. In this work we propose a theoretical investigation based on molecular dynamics (MD) simulations and hybrid quantum mechanics/molecular mechanics (QM/MM) optimizations, aimed to shed light on several Fe(III)-MC6 structural features and to validate the de novo designed fold. Key structural elements were analyzed to achieve indirect insight relevant to understand Fe(III)-MC6 catalytic performances in solution. Extensive MD simulations showed a partial stability of the “sandwich” fold in water solution. The smaller peptide chain bonded to the heme revealed a high conformational freedom, which promoted the exposition of the heme distal side to the solvent. Regarding the accessibility of water molecules, even in Fe(III)-MC6 “closed” structure the heme cavity appeared hydrated, suggesting an easy accessibility by exogenous ligands. Fe(III)-MC6 structure in both high and low spin states was then further characterized through hybrid QM/MM optimizations. In particular, an accurate description of the active site structure was obtained, allowing a direct comparison of Fe(III)-MC6 coordination environment with that observed in the Horseradish Peroxidase crystal structures. Our results suggest a structural similarity between Fe(III)-MC6 and the natural enzyme. This study supports the interpretation of data from experimental Fe(III)-MC6 structural and functional characterization and the rational design of new artificial mimics with improved catalytic performances.

Unveiling the structure of a novel artificial heme-enzyme with peroxidase-like activity: A theoretical investigation / Perrella, Fulvio; Raucci, Umberto; Chiariello, Maria Gabriella; Chino, Marco; Maglio, Ornella; Lombardi, Angela; Rega, Nadia; Lombardi, Angelina. - In: BIOPOLYMERS. - ISSN 0006-3525. - 190:10(2018), p. e23225. [10.1002/bip.23225]

Unveiling the structure of a novel artificial heme-enzyme with peroxidase-like activity: A theoretical investigation

PERRELLA, FULVIO;Raucci, Umberto;Chiariello, Maria Gabriella;Chino, Marco;Maglio, Ornella;Lombardi, Angela;Rega, Nadia
;
2018

Abstract

Fe(III)-Mimochrome VI (MC6) is a recently reported artificial heme-peptide conjugate system with a high peroxidase-like activity. By design, its structure features a five-coordinated Fe(III)-deuteroporphyrin active site, embedded in a compact α-helix–heme–α-helix “sandwich” motif. Up to now, no detailed MC6 structural characterization is available. In this work we propose a theoretical investigation based on molecular dynamics (MD) simulations and hybrid quantum mechanics/molecular mechanics (QM/MM) optimizations, aimed to shed light on several Fe(III)-MC6 structural features and to validate the de novo designed fold. Key structural elements were analyzed to achieve indirect insight relevant to understand Fe(III)-MC6 catalytic performances in solution. Extensive MD simulations showed a partial stability of the “sandwich” fold in water solution. The smaller peptide chain bonded to the heme revealed a high conformational freedom, which promoted the exposition of the heme distal side to the solvent. Regarding the accessibility of water molecules, even in Fe(III)-MC6 “closed” structure the heme cavity appeared hydrated, suggesting an easy accessibility by exogenous ligands. Fe(III)-MC6 structure in both high and low spin states was then further characterized through hybrid QM/MM optimizations. In particular, an accurate description of the active site structure was obtained, allowing a direct comparison of Fe(III)-MC6 coordination environment with that observed in the Horseradish Peroxidase crystal structures. Our results suggest a structural similarity between Fe(III)-MC6 and the natural enzyme. This study supports the interpretation of data from experimental Fe(III)-MC6 structural and functional characterization and the rational design of new artificial mimics with improved catalytic performances.
2018
Unveiling the structure of a novel artificial heme-enzyme with peroxidase-like activity: A theoretical investigation / Perrella, Fulvio; Raucci, Umberto; Chiariello, Maria Gabriella; Chino, Marco; Maglio, Ornella; Lombardi, Angela; Rega, Nadia; Lombardi, Angelina. - In: BIOPOLYMERS. - ISSN 0006-3525. - 190:10(2018), p. e23225. [10.1002/bip.23225]
Unveiling the structure of a novel artificial heme-enzyme with peroxidase-like activity: A theoretical investigation / Perrella, Fulvio; Raucci, Umberto; Chiariello, Maria Gabriella; Chino, Marco; Maglio, Ornella; Lombardi, Angela; Rega, Nadia; Lombardi, Angelina. - In: BIOPOLYMERS. - ISSN 0006-3525. - 190:10(2018), p. e23225. [10.1002/bip.23225]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11588/723116
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