Unveiling the Transient Protein-Protein Interactions that Modulate the Activity of Estrogen Receptor(ER)-α by Human Lemur Tyrosine Kinase-3 (LMTK3) Domain: An In Silico Study

Author(s): Venkata Satish Kumar Mattaparthi*, Himakshi Sarma

Journal Name: Current Proteomics

Volume 14 , Issue 2 , 2017

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Graphical Abstract:


Background: Estrogen receptor-α positive breast cancer is the most common dreadful disease and leading cause of death among women. In majority of human breast cancer, the interactions between kinases and ERα are considered to be critical in signaling pathway. Many kinases are known to regulate ERα activity. Recently Lemur tyrosine kinase-3 was identified as predictive oncogenic ERα regulator with a vital role in endocrine resistance. The role of LMTK3 in ERα regulation can be known by studying the interactions between them.

Objectives: To understand the transient interactions between ER-α and LMTK3 using computational technique.

Method: ERα -LMTK3 complex structure was obtained using PatchDock server. The interacting residues and interface area between ERα and LMTK3 were identified using PDBsum. Molecular dynamics simulation was used to study the conformational dynamics of ERα -LMTK3 complex.

Result: The approximate interface area of ERα-LMTK3 was found to be 3175 Å2 with atomic contact energy of 191.77 kcal/mol. PDBsum results revealed that some of the residues in C-terminal region of LMTK3 displayed non-bonding interactions with the residues in the phosphorylation sites (Ser104 and Ser106) of ERα. We noticed the total number of interface residues in ERα-LMTK3 complex to be 50 and the interface area for ERα as well as LMTK3 chain involved in interaction to be more than 2380 Å2. From conformational dynamics study, ERα-LMTK3 complex structure was found to be stable.

Conclusion: The outcomes of the current study enhance the understanding of interactions between ERα and LMTK3 which are thought to be critical in signaling pathway in majority of human breast cancers.

Keywords: Breast cancer, endocrine resistance, molecular dynamics simulation, PatchDock, PDBsum.

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Article Details

Year: 2017
Published on: 11 April, 2017
Page: [157 - 164]
Pages: 8
DOI: 10.2174/1570164614666161206164330
Price: $25

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