Effects of Single Nucleotide Polymorphisms on Human N-Acetyltransferase 2 Structure and Dynamics by Molecular Dynamics Simulation
2011

Effects of SNPs on Human N-Acetyltransferase 2 Structure and Dynamics

publication Evidence: moderate

Author Information

Author(s): Rajasekaran M., Abirami Santhanam, Chen Chinpan

Primary Institution: Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan

Hypothesis

How do single nucleotide polymorphisms (SNPs) affect the structure and dynamics of the human N-acetyltransferase 2 (NAT2) enzyme?

Conclusion

The study provides a structural basis for the reduced catalytic activity and protein levels associated with specific NAT2 polymorphisms.

Supporting Evidence

  • The study used molecular dynamics simulations to analyze the effects of SNPs on NAT2.
  • Results showed that mutations affected the flexibility and orientation of key functional regions in the protein.
  • Electrostatic potential changes in mutants may lead to aggregation and reduced protein levels.

Takeaway

This study looks at how tiny changes in a protein can affect how it works, which is important for understanding how some people process certain drugs differently.

Methodology

Multiple molecular dynamics simulations were performed on wild-type and mutant NAT2 structures to analyze structural and dynamical effects.

Limitations

The study primarily focuses on a limited number of SNPs and their effects, which may not encompass all variations in NAT2.

Digital Object Identifier (DOI)

10.1371/journal.pone.0025801

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