Molecular Dynamics Simulation Reveal the Structure–Activity Relationships of Kainoid Synthases DOI Creative Commons

Zeyu Fan,

Xin‐Hao Li, Ruoyu Jiang

et al.

Marine Drugs, Journal Year: 2024, Volume and Issue: 22(7), P. 326 - 326

Published: July 22, 2024

Kainoid synthases are key enzymes in the biosynthesis of kainoids. Kainoids, as represented by DA and KA, a class naturally occurring non-protein amino acids with strong neurotransmitter activity mammalian central nervous system. Marine algae kainoid include PnDabC from diatoms, which synthesizes domoic acid (DA), DsKabC GfKabC red algae, synthesize kainic (KA). Elucidation catalytic mechanism is great significance for rational design better biocatalysts to promote industrial production kainoids use new drugs. Through modeling, molecular docking, dynamics simulations, we investigated conformational synthases. We found that synthase complexes showed different stability simulation, binding processes significant transformations synthase. The residues involved specific interactions substrate contributed energy throughout simulation process. Binding energy, relaxed active pocket, electrostatic potential number rotation aromatic interacting substrates during catalysis, frequency hydrogen bonds between individual functional groups revealed structure-activity relationships affected degree promiscuity Our research enriches understanding has guiding their design.

Language: Английский

Molecular Dynamics Simulation Reveal the Structure–Activity Relationships of Kainoid Synthases DOI Creative Commons

Zeyu Fan,

Xin‐Hao Li, Ruoyu Jiang

et al.

Marine Drugs, Journal Year: 2024, Volume and Issue: 22(7), P. 326 - 326

Published: July 22, 2024

Kainoid synthases are key enzymes in the biosynthesis of kainoids. Kainoids, as represented by DA and KA, a class naturally occurring non-protein amino acids with strong neurotransmitter activity mammalian central nervous system. Marine algae kainoid include PnDabC from diatoms, which synthesizes domoic acid (DA), DsKabC GfKabC red algae, synthesize kainic (KA). Elucidation catalytic mechanism is great significance for rational design better biocatalysts to promote industrial production kainoids use new drugs. Through modeling, molecular docking, dynamics simulations, we investigated conformational synthases. We found that synthase complexes showed different stability simulation, binding processes significant transformations synthase. The residues involved specific interactions substrate contributed energy throughout simulation process. Binding energy, relaxed active pocket, electrostatic potential number rotation aromatic interacting substrates during catalysis, frequency hydrogen bonds between individual functional groups revealed structure-activity relationships affected degree promiscuity Our research enriches understanding has guiding their design.

Language: Английский

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