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

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.
Authors	Panneerselvam Manivel, Jayaraman Muthukumaran, Muthu Kannan, Ramadas Krishna
Journal	Journal of molecular modeling (J Mol Model) Vol. 17 Issue 2 Pg. 251-63 (Feb 2011) ISSN: 0948-5023 [Electronic] Germany
PMID	20437261 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References	Ankyrins HSP70 Heat-Shock Proteins Neoplasm Proteins SNCG protein, human alpha-Synuclein gamma-Synuclein BUB1 protein, human Bub1 spindle checkpoint protein Protein Serine-Threonine Kinases
Topics	Amino Acid Sequence Ankyrins (metabolism) Breast Neoplasms (metabolism) Female HSP70 Heat-Shock Proteins (metabolism) Humans Models, Molecular Mutation Neoplasm Proteins (antagonists & inhibitors, chemistry, metabolism) Protein Conformation Protein Serine-Threonine Kinases (metabolism) Sequence Alignment alpha-Synuclein (chemistry) gamma-Synuclein (antagonists & inhibitors, chemistry, metabolism)

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