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Structural stability of myoglobin and glycomyoglobin: a comparative molecular dynamics simulation study

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Abstract

Glycoproteins are formed as the result of enzymatic glycosylation or chemical glycation in the body, and produced in vitro in industrial processes. The covalently attached carbohydrate molecule(s) confer new properties to the protein, including modified stability. In the present study, the structural stability of a glycoprotein form of myoglobin, bearing a glucose unit in the N-terminus, has been compared with its native form by the use of molecular dynamics simulation. Both structures were subjected to temperatures of 300 and 500 K in an aqueous environment for 10 ns. Changes in secondary structures and RMSD were then assessed. An overall higher stability was detected for glycomyoglobin, for which the most stable segments/residues were highlighted and compared with the native form. The simple addition of a covalently bound glucose is suggested to exert its stabilizing effect via increased contacts with surrounding water molecules, as well as a different pattern of interactions with neighbor residues.

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Acknowledgments

This study was supported by the Endocrinology and Metabolism Research Institute and performed in its Modeling and Simulation Lab.

Conflict of interest

The authors declare that they have no conflicts of interest to disclose.

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Authors and Affiliations

  1. School of Chemistry, College of Science, University of Tehran, Tehran, Iran

    Joulia Alizadeh-Rahrovi & Alireza Shayesteh

  2. Biosensor Research Center, Endocrinology and Metabolism Molecular-Cellular Sciences Institute, Tehran University of Medical Sciences, Shariati Hospital, North Kargar Avenue, 1411413137, Tehran, Iran

    Azadeh Ebrahim-Habibi

  3. Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran

    Azadeh Ebrahim-Habibi

Authors
  1. Joulia Alizadeh-Rahrovi
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  2. Alireza Shayesteh
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Corresponding authors

Correspondence to Alireza Shayesteh or Azadeh Ebrahim-Habibi.

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Fig. S1

Snapshots of native and glycated form of human myoglobin simulations extracted at first and last time points at 500 K. Ribbons are α-helices. (GIF 54 kb)

High resolution image (TIFF 163 kb)

Fig. S2

Three-dimensional representation of residues located at 4.5 Å of Gly1 in (a) Mb and (b) GMb over time in ten sampled structures. (GIF 122 kb)

(GIF 125 kb)

High-resolution image (TIFF 441 kb)

(TIFF 511 kb)

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Alizadeh-Rahrovi, J., Shayesteh, A. & Ebrahim-Habibi, A. Structural stability of myoglobin and glycomyoglobin: a comparative molecular dynamics simulation study. J Biol Phys 41, 349–366 (2015). https://doi.org/10.1007/s10867-015-9383-2

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  • DOI: https://doi.org/10.1007/s10867-015-9383-2

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