P01-15
Dynamic Relationship Between the Entrance to the Ligand Binding Site and the Dimer Interface in MAO-B
Yoshitaka TADOKORO *1, Shota SHIMOGOCHI1, Ryota KIYOOKA1, Masaki OTAWA3, Naoyuki MIYASHITA1, 2
1Graduate School of Biology-Oriented Science and Technology, KINDAI University
2Faculty of Biology-Oriented Science and Technology, KINDAI University
3School of Physical Sciences, SOKENDAI
( * E-mail: tadoyoshi@miyashita-lab.net )
Monoamine oxidase B (MAO-B) is located on the outer membrane of mitochondria and is known to catalyze the oxidation of dopamine [1-2]. It is associated with neurological diseases such as Parkinson’s disease and other neurological disorders. Recently, the development of Positron Emission Tomography (PET) tracers for disease diagnosis has garnered attention [3-4]. PET tracers targeting MAO-B have also been developed [4]. MAO-B typically adopts a dimeric conformation in the mitochondrial membrane. The ligand entrance gates of the MAO-B dimer are small and appear “semi-closed” in the structure determined by X-ray crystallography. The detailed mechanisms governing the entrance gate to the binding site remain unclear. To investigate the dynamics of the entrance gate for ligand entry into the binding site, we performed molecular dynamics simulations of MAO-B in the mitochondrial membrane, both with and without PET tracers. We found large entrance gates in the MAO-B dimer, and these gates exhibited asymmetry within the dimer. The dynamics of these large entrance gates were linked to the dynamics of the dimer interface, with the slight asymmetry of the dimer interface dynamics contributing to the asymmetric dynamics of the entrance gates.
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