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Impact of glycosylation on stability, structure and unfolding of soybean agglutinin (SBA): an insight from thermal perturbation molecular dynamics simulations

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Abstract

Glycosylation has been recognized as one of the most prevalent and complex post-translational modifications of proteins involving numerous enzymes and substrates. Its effect on the protein conformational transitions is not clearly understood yet. In this study, we have examined the effect of glycosylation on protein stability using molecular dynamics simulation of legume lectin soybean agglutinin (SBA). Its glycosylated moiety consists of high mannose type N-linked glycan (Man9GlcNAc2). To unveil the structural perturbations during thermal unfolding of these two forms, we have studied and compared them to the experimental results. From the perspective of dynamics, our simulations revealed that the nonglycosylated monomeric form is less stable than corresponding glycosylated form at normal and elevated temperatures. Moreover, at elevated temperature thermal destabilization is more prominent in solvent exposed loops, turns and ends of distinct β sheets. SBA maintains it folded structure due to some important saltbridges, hydrogen bonds and hydrophobic interactions within the protein. The reducing terminal GlcNAc residues interact with the protein residues VAL161, PRO182 and SER225 via hydrophobic and via hydrogen bonding with ASN 9 and ASN 75. Our simulations also revealed that single glycosylation (ASN75) has no significant effect on corresponding cis peptide angle orientation. This atomistic description might have important implications for understanding the functionality and stability of Soybean agglutinin.

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Abbreviations

SBA:

Soybean agglutinin

Gly_SBA:

Glycosylated soybean agglutinin

Non Gly_SBA:

Non glycosylated soybean agglutinin

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Acknowledgments

This work is supported by a project funded by the Department of Biotechnology, Government of India [No. BT/PR13421/BID/07/307/2009]. AS holds Bhatnagar Fellowship of the Council of Scientific and Industrial Research, India

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Authors and Affiliations

  1. Department of Chemistry, University of Calcutta, 92, A. P. C. Road, Kolkata, 700 009, India

    Swagata Halder & Chaitali Mukhopadhyay

  2. Molecular Biophysics Unit, Indian Institute of Science, Bangalore, 560 012, India

    Avadhesha Surolia

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  1. Swagata Halder
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  2. Avadhesha Surolia
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  3. Chaitali Mukhopadhyay
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Correspondence to Avadhesha Surolia or Chaitali Mukhopadhyay.

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Halder, S., Surolia, A. & Mukhopadhyay, C. Impact of glycosylation on stability, structure and unfolding of soybean agglutinin (SBA): an insight from thermal perturbation molecular dynamics simulations. Glycoconj J 32, 371–384 (2015). https://doi.org/10.1007/s10719-015-9601-y

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