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Arch Biochem Biophys. 2015 Nov 1;585:1-9. doi: 10.1016/j.abb.2015.09.005. Epub 2015 Sep 9.

Enhanced heme accessibility in horse heart mini-myoglobin: Insights from molecular modelling and reactivity studies.

Author information

1
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.
2
UCD Conway Institute of Biomolecular and Biomedical Research, School of Medicine and Medical Science, University College Dublin, Belfield Dublin 4, Ireland.
3
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.
4
Biosciences and Biotechnology School, University of Camerino, Via Gentile III da Varano, I-62032 Camerino (MC), Italy.
5
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.

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.

KEYWORDS:

Mini-myoglobin; Molecular modelling; Protein matrix tunnels; Reactivity properties; Structure

PMID:
26363214
DOI:
10.1016/j.abb.2015.09.005
[Indexed for MEDLINE]

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