Background: In many human diseases protein kinase are known to play a central role. Protein
kinases phosphorylate its substrates and they themselves regulated through phosphorylation of
their activation loop and become catalytically active. LMTK3 is an oncogenic protein kinase, implicated
in breast cancer progression and endocrine resistance. Recent report says phosphorylation of
LMTK3 by CDK5 results in breast cancer tumor progression. Thereby information about interface
residues and probable phosphorylation site on LMTK3 is critical.
Objective: To understand the transient protein – protein interactions between CDK5 and LMTK3 using
Methods: LMTK3 structure was superimposed with known kinases to determine the probable activation
segment and phosphorylation sites in LMTK3. PatchDock was used to obtain CDK5-LMTK3 complex
structure. PDBsum server was used to identify the interface residues between CDK5 and LMTK3. The
stability of CDK5-LMTK3 complex was studied using Molecular dynamics (MD) simulation.
Results: From PatchDock, interface area between CDK5-LMTK3 complex was found to be 2081 Å2
with atomic contact energy of -228.80 kcal/mol. PDBsum result reveal that, CDK5 interact and displayed
non-bonding interactions with the probable phosphorylation sites of LMTK3. Total number of
interface residues across CDK5-LMTK3 was found to be around 50 and the interface area found to be
1274 Å2 (in CDK5) and 1224 Å2 (in LMTK3). From MD simulation, CDK5-LMTK3 complex was
found to be stable.
Conclusion: This study enhances the understanding of interactions between CDK5 and LMTK3 that
may be helpful in understanding the LMTK3 phosphorylation by CDK5 which is considered to be a
new cellular pathway in breast cancer tumor progression.