title: Enhanced heme accessibility in horse heart mini-myoglobin: Insights from molecular modelling and reactivity studies.
abstract: Mini-myoglobin (mini-HHMb) is a fragment of horse-heart myoglobin (HHMb) considered to be the prototype of the product encoded by the central exon of the HHMb gene. For this reason, mini-HHMb has been studied extensively showing that carbonylation and oxygenation properties of the ferrous form are similar to those of the full-length protein, while kinetics and thermodynamics of azide binding to the ferric form are significantly different from those of HHMb. To analyze the structure-function relationships in mini-HHMb and the role of conformational fluctuations in ligand accessibility, the molecular model of mini-HHMb has been built and refined by molecular dynamics simulations, and analyzed in parallel with that of full length HHMb. Moreover, imidazole binding parameters of ferric mini-HHMb and HHMb have been determined. Furthermore, structural data of ferric mini-HHMb and HHMb have been correlated with the imidazole and previously determined azide binding properties. Present results indicate that, despite the extensive trimming, the heme-α-helices E-F substructure is essentially unaltered in mini-HHMb with respect to HHMb. However, the heme-Fe atom displays an enhanced accessibility in mini-HHMb, which may affect both ligand association and dissociation kinetics.
authors.affiliation: Department of Sciences, Roma Tre University, Viale Guglielmo Marconi 446, I-00146 Roma, Italy; National Institute of Nuclear Physics, Roma Tre University Section, Via Della Vasca Navale 84, I-00146 Roma, Italy. Electronic address: polticel@uniroma3.it.
authors.forename: Fabio
authors.initials: F
authors.lastname: Polticelli
authors.affiliation: UCD Conway Institute of Biomolecular and Biomedical Research, School of Medicine and Medical Science, University College Dublin, Belfield Dublin 4, Ireland.
authors.forename: Veranika
authors.initials: V
authors.lastname: Zobnina
authors.affiliation: Department of Clinical Sciences and Translational Medicine, University of Roma "Tor Vergata", Via Montpellier 1, I-00133 Roma, Italy; Interuniversity Consortium for the Research on Chemistry of Metals in Biological Systems, Via Celso Ulpiani 1, I-70125 Bari, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Ciaccio
authors.affiliation: Biosciences and Biotechnology School, University of Camerino, Via Gentile III da Varano, I-62032 Camerino (MC), Italy.
authors.forename: Giampiero
authors.initials: G
authors.lastname: de Sanctis
authors.affiliation: Interdepartmental Laboratory for Electron Microscopy, Roma Tre University, Via Della Vasca Navale 79, I-00146 Roma, Italy; Institute of Protein Biochemistry, CNR, Via Pietro Castellino 111, I-80181 Napoli, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Ascenzi
authors.affiliation: Department of Clinical Sciences and Translational Medicine, University of Roma "Tor Vergata", Via Montpellier 1, I-00133 Roma, Italy; Interuniversity Consortium for the Research on Chemistry of Metals in Biological Systems, Via Celso Ulpiani 1, I-70125 Bari, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Coletta
mesh_terms: D000818:Animals; D001386:Azides / Q000737:chemistry; D006418:Heme / Q000737:chemistry*; D006736:Horses; D007093:Imidazoles / Q000737:chemistry*; D007501:Iron / Q000737:chemistry*; D007700:Kinetics; D008024:Ligands; D056004:Molecular Dynamics Simulation; D009206:Myocardium / Q000737:chemistry; D009211:Myoglobin / Q000737:chemistry*; D010446:Peptide Fragments / Q000737:chemistry*; D017433:Protein Structure, Secondary; D011994:Recombinant Proteins / Q000737:chemistry; D013816:Thermodynamics
chemical_list: D001386:Azides; D007093:Imidazoles; D008024:Ligands; D009211:Myoglobin; D010446:Peptide Fragments; D011994:Recombinant Proteins; C056954:mini-myoglobin; D006418:Heme; C029899:imidazole; D007501:Iron
keywords: Mini-myoglobin; Molecular modelling; Protein matrix tunnels; Reactivity properties; Structure