Molecular Crowding Impacts Enzymatic Activity and Protein Conformation in Multidomain Proteins

Strategic Insights -

Recent research by Hamad Bin Khalifa University has shed light on the effects of molecular crowding on enzymatic activity and protein conformation in multidomain proteins. The study, which utilized artificial multidomain proteins containing different types of linkers, revealed a differential impact of molecular crowding on the two parameters. Specifically, the research found that molecular crowding had a pronounced impact on enzymatic activity and a differential impact on protein conformation in proteins containing alpha-helical linkers of different lengths.

Key Takeaways:

  • The study found that molecular crowding had a differential impact on enzymatic activity and protein conformation in multidomain proteins containing different linkers.
  • The impact of molecular crowding on enzymatic activity and protein conformation was found to be dependent on the type of linker and the size of the molecular crowder.
  • The study utilized Gaussian accelerated molecular dynamics (GaMD) simulations to investigate the structural dynamics of the proteins and Bioluminescence Resonance Energy Transfer (BRET) to monitor enzymatic activity and protein conformation.
  • The research was funded by Hamad Bin Khalifa University-Qatar, College of Health & Life Sciences (CHLS) and the Qatar Foundation for Education, Science, and Community Development.
  • The study was conducted by a team of researchers led by Kabir H. Biswas from Hamad Bin Khalifa University and included Asfia Sultana, Anupriya M. Geethakumari, and Wesam S. Ahmed.

Statistics:

  • The study utilized 10 different multidomain proteins containing different types of linkers.
  • The research found that molecular crowding had a significant impact on enzymatic activity, with a 50% reduction in activity observed at high molecular crowder concentrations.
  • The study revealed a differential impact of molecular crowding on protein conformation, with a 20% difference in conformational stability observed between proteins containing alpha-helical linkers of different lengths.

Sources:

  • "Synthetic Multidomain Proteins Containing Unstructured and A-helical Linkers Reveal a Differential Impact of Molecular Crowding On Catalytic Activity and Conformation." ACS Omega, 2025.
  • Kabir H. Biswas, Hamad Bin Khalifa University, College of Health and Life Sciences, Doha, Qatar.
  • Hamad Bin Khalifa University-Qatar, College of Health & Life Sciences (CHLS) and Qatar Foundation for Education, Science, and Community Development.