Monoamine oxidase b: Difference between revisions
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{{STRUCTURE_1gos| PDB=1gos | SIZE=300| SCENE= |right| CAPTION=Monoamine oxidase B complex with FAD and methanaminium, [[1gos]] }} | {{STRUCTURE_1gos| PDB=1gos | SIZE=300| SCENE= |right| CAPTION=Monoamine oxidase B complex with FAD and methanaminium, [[1gos]] }} | ||
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== Structure == | == Structure == | ||
Structurally, MAO-B is a dimer with each monomer composed of 520 amino acids. The sequence <scene name='User:Martha_Blakely/Sandbox_1/Alpha_helices/1'>489-520</scene> forms a helix on each monomer that is responsible for the attachment to the outer-membrane of mitochondria. This α-helix resides in the lipid bilayer. In addition to the C-terminal helices, other hydrophobic side chains such as <scene name='User:Martha_Blakely/Sandbox_1/Pro109ile110/1'>Pro109 and Ile110</scene> also contribute to attachment. | Structurally, MAO-B is a dimer with each monomer composed of 520 amino acids. The sequence <scene name='User:Martha_Blakely/Sandbox_1/Alpha_helices/1'>489-520</scene> forms a helix on each monomer that is responsible for the attachment to the outer-membrane of mitochondria. This α-helix resides in the lipid bilayer. In addition to the C-terminal helices, other hydrophobic side chains such as <scene name='User:Martha_Blakely/Sandbox_1/Pro109ile110/1'>Pro109 and Ile110</scene> also contribute to attachment. | ||
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==Inhibition== | ==Inhibition== | ||
Both reversible and irreversible inhibitors have been developed for MAO-B. Irreversible inhibitors form a covalent bond to the FAD cofactor in the enzyme active site, permanently deactivating it. Concentrations of the inhibitor and the possible substrates determine whether a reversible inhibitor binds to the enzyme. <scene name='1gos/Rasagiline_bound_to_mao-b/1'>Rasagiline</scene> and <scene name='1gos/Deprenyl_bound_to_mao-b/2'>deprenyl</scene> (also seleginine) are both FDA-approved irreversible inhibitors used for the inhibition of MAO-B. They both are categorized as propargylamines. Rasagiline is much more selective for MAO-B than MAO-A. Only its R isomer is pharmacologically active while its S isomer is not. Under normal administration, deprenyl is selective for MAO-B, but when deprenyl is administered in large amounts, its selectivity for MAO-B decreases. In this case, it also inhibits MAO-A. <scene name='1gos/Bound_with_safinamide/2'>Safinamide</scene> is an example of a reversible inhibitor for MAO-B. Other known inhibitors are derived from pyrazole, xanthone, and pirlindole. | Both reversible and irreversible inhibitors have been developed for MAO-B. Irreversible inhibitors form a covalent bond to the FAD cofactor in the enzyme active site, permanently deactivating it. Concentrations of the inhibitor and the possible substrates determine whether a reversible inhibitor binds to the enzyme. <scene name='1gos/Rasagiline_bound_to_mao-b/1'>Rasagiline</scene> and <scene name='1gos/Deprenyl_bound_to_mao-b/2'>deprenyl</scene> (also seleginine) are both FDA-approved irreversible inhibitors used for the inhibition of MAO-B. They both are categorized as propargylamines. Rasagiline is much more selective for MAO-B than MAO-A. Only its R isomer is pharmacologically active while its S isomer is not. Under normal administration, deprenyl is selective for MAO-B, but when deprenyl is administered in large amounts, its selectivity for MAO-B decreases. In this case, it also inhibits MAO-A. <scene name='1gos/Bound_with_safinamide/2'>Safinamide</scene> is an example of a reversible inhibitor for MAO-B. Other known inhibitors are derived from pyrazole, xanthone, and pirlindole. | ||