Unveiling the structure of a novel artificial heme-enzyme with peroxidase-like activity: A theoretical investigation(52 visite) Perrella F, Raucci U, Chiariello MG, Chino M, Maglio O, Lombardi A, Rega N
Impact factor: 1.908, Impact factor a 5 anni: 2.563
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Parole chiave: Artificial Heme-Enzyme, Hybrid Qm, Mm Methods, Molecular Dynamics,
*** IBB - CNR *** Dipartimento di Scienze Chimiche, Universita di Napoli Federico II, Complesso Universitario di M.S.Angelo, via Cintia, Napoli, 80126, Italy., IBB-CNR, Via Mezzocannone 16, Napoli, 80134, Italy., CRIB Center for Advanced Biomaterials for Healthcare, Piazzale Tecchio, Napoli, 80125, Italy.,
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 alpha-helix-heme-alpha-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.
173 Records (168 escludendo Abstract e Conferenze). Impact factor totale: 664.094 (642.011 escludendo Abstract e Conferenze). Impact factor a 5 anni totale: 703.829 (681.593 escludendo Abstract e Conferenze).