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
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