QM/MM Study of Catalytic Mechanism of LSD1
2011

Understanding the Catalytic Mechanism of LSD1

publication Evidence: high

Author Information

Author(s): Kong Xiangqian, Ouyang Sisheng, Liang Zhongjie, Lu Junyan, Chen Liang, Shen Bairong, Li Donghai, Zheng Mingyue, Li Keqin Kathy, Luo Cheng, Jiang Hualiang

Primary Institution: State Key Laboratory of Drug Research, Drug Discovery and Design Center, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China

Hypothesis

The study investigates the catalytic mechanism of lysine-specific demethylase 1 (LSD1) during the reductive half-reaction in demethylation.

Conclusion

The study confirms that the reductive half-reaction of LSD1 follows a direct hydride transfer mechanism.

Supporting Evidence

  • LSD1 is crucial for various biological processes including cell proliferation and embryonic development.
  • The study provides insights into the molecular mechanism of LSD1, which is important for drug discovery.
  • MD simulations highlighted the role of specific residues in stabilizing the catalytic environment.

Takeaway

LSD1 is an important enzyme that helps control gene activity by removing certain chemical tags from proteins, and this study explains how it does that.

Methodology

The study used molecular modeling, molecular dynamics simulations, and quantum mechanics/molecular mechanics calculations to explore the catalytic mechanism.

Digital Object Identifier (DOI)

10.1371/journal.pone.0025444

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