Interaction between PET tracer and the specific residues around the gate of the open form of Monoamine Oxidase B (MAO-B)

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Monoamine Oxidase B (MAO-B) is the enzyme that metabolizes a monoamine neurotransmitter. Recently, a PET tracer targeting MAO-B, SMBT-1, has been developed as the biomarker of neurodegenerative diseases. However, the detailed binding mode of SMBT-1 has not been clear. To clarify the binding mode of SMBT-1 on MAO-B, we performed the molecular dynamics (MD) simulations of MAO-B in the outer mitochondrial membrane and the complex of MAO-B to SMBT-1, and the docking simulation of MAO-B with SMBT-1. We found that the Leu88, Leu171, Ile199, and Tyr326 around the substrate-binding site interact with SMBT-1. These hydrophobic residues mainly support the two aromatic rings of the center of SMBT-1, making the stable binding of SMBT-1.