Investigating pH-induced conformational switch in PIM-1: An integrated multi spectroscopic and MD simulation study

Area of Science:

• Biochemistry
• Structural Biology
• Pharmacology

Background:

• PIM-1 (serine/threonine kinase) is a key factor in various cancers, including prostate and breast cancer.
• Understanding PIM-1's structure is crucial for developing targeted cancer therapies.

Purpose of the Study:

• To investigate the structural and conformational changes of PIM-1 at different pH levels.
• To correlate pH-induced changes with PIM-1's enzymatic activity and stability.

Main Methods:

• Spectroscopic techniques (UV-Vis, CD) to assess protein structure.
• Kinase assays to determine enzyme activity across pH ranges.
• All-atom molecular dynamics (MD) simulations to analyze structural stability.

Main Results:

• PIM-1 maintains secondary and tertiary structures between pH 7.0-9.0.
• Protein aggregation observed at acidic pH (5.0-6.0).
• Optimal PIM-1 activity is within the pH range of 7.0-9.0, confirmed by MD simulations showing native conformation in alkaline conditions.

Conclusions:

• PIM-1 exhibits pH-dependent stability and activity, with optimal function in neutral to alkaline environments.
• Acidic pH induces aggregation and conformational changes, affecting kinase function.
• Findings provide insights into PIM-1's role in cellular homeostasis and disease under varying pH.