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Insight into residues involved in the structure and function of the breast cancer associated protein human gamma synuclein

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Abstract

Aberrantly expressed human gamma synuclein (SNCG) interacts with BubR1 and heat shock protein 70 (Hsp70) in late stages of breast and ovarian cancer. This interaction is essential for progression, development and survival of cancer cells. A short, synthetically designed ankyrin-repeat-containing peptide (ANK peptide) was proven to inhibit the activity of SNCG. However, the potential binding site residues of SNCG responsible for its oncogenic function have not been reported so far. The objectives of this study were to generate a three-dimensional model of SNCG and to identify the key residues involved in interaction with BubR1, ANK peptide and Hsp70. Our study is the first attempt to report the specific binding of SNCG with the TPR motif of BubR1 and the 18kDa region of Hsp70. Our findings provide novel insights into the mechanism of interaction of SNCG, and can act as a basis for the ongoing drug design and discovery process aimed at treating breast and ovarian cancer.

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Acknowledgments

Research in the Laboratory of Structure Biology is supported by grants from University Grants Commission (UGC), Government of India, New Delhi, India. R.K. thanks the Centre for Bioinformatics, Pondicherry University, India.

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Authors and Affiliations

  1. Centre of Excellence in Bioinformatics, School of Life Sciences, Pondicherry University, Puducherry, 605 014, India

    Panneerselvam Manivel, Jayaraman Muthukumaran, Muthu Kannan & Ramadas Krishna

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  1. Panneerselvam Manivel
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  2. Jayaraman Muthukumaran
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  3. Muthu Kannan
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  4. Ramadas Krishna
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Correspondence to Ramadas Krishna.

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Manivel, P., Muthukumaran, J., Kannan, M. et al. Insight into residues involved in the structure and function of the breast cancer associated protein human gamma synuclein. J Mol Model 17, 251–263 (2011). https://doi.org/10.1007/s00894-010-0718-4

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  • DOI: https://doi.org/10.1007/s00894-010-0718-4

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