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Current Proteomics

Author(s): Mahboubeh Zarei, Soudabeh Sabetian, Mohammad Reza Rahbar and Manica Negahdaripour*

DOI: 10.2174/1570164619666220513123509

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Methanol and Sorbitol Affect the Molecular Dynamics of Arginine Deiminase: Insights for Improving its Stability

Page: [380 - 387] Pages: 8

  • * (Excluding Mailing and Handling)

Abstract

Background: The arginine deiminase enzyme of Mycoplasma arginini (MaADI) is a potential anti-cancer agent for treating arginine-auxotrophic cancers. Investigating the protein stability in the presence of osmolytes can help to increase protein stability under various stressed conditions.

Methods: In this study, the stability and dynamics of MaADI were investigated in pure water and solutions of 1 M sorbitol, 10% (v/v) methanol, and 50% (v/v) methanol using molecular dynamics simulation.

Results: Sorbitol was found to stabilize the protein, whereas high-concentrated methanol destabilized it. Sorbitol molecules interacted with the protein through hydrogen bonding and reduced the protein fluctuations. At 50% methanol, the flexibility of regions 4-8, 195-201, 314-324, and 332- 337 in the MaADI was increased, whereas residues 195-201 showed the highest variations.

Conclusion: Thus, these regions of MaADI, especially 195-201, are the most sensitive regions in the presence of denaturing agents and can be subjected to protein engineering to improve the stability of MaADI.

Keywords: Arginine deiminase, protein stability, sorbitol, methanol, molecular dynamics simulation, ADI.

Graphical Abstract

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