2c65: Difference between revisions
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==Overview== | ==Overview== | ||
Monoamine oxidases A and B (MAO A and B) catalyze the degradation of, neurotransmitters and represent drug targets for the treatment of, neurodegenerative disorders. Rasagiline is an irreversible, MAO, B-selective inhibitor that has been approved as a novel anti-Parkinson's, drug. In this study, we investigate the inhibition of recombinant human, MAO A and MAO B by several rasagiline analogues. Different substituents, added onto the rasagiline scaffold alter the binding affinity depending on, the position on the aminoindan ring and on the size of the substituent., Compounds with a hydroxyl group on either the C4 or the C6 atom inhibit, both isozymes, whereas a bulkier substituent such as a carbamate is, tolerated only at the C4 position. The 1.7 A crystal structure of MAO B in, complex .. | Monoamine oxidases A and B (MAO A and B) catalyze the degradation of, neurotransmitters and represent drug targets for the treatment of, neurodegenerative disorders. Rasagiline is an irreversible, MAO, B-selective inhibitor that has been approved as a novel anti-Parkinson's, drug. In this study, we investigate the inhibition of recombinant human, MAO A and MAO B by several rasagiline analogues. Different substituents, added onto the rasagiline scaffold alter the binding affinity depending on, the position on the aminoindan ring and on the size of the substituent., Compounds with a hydroxyl group on either the C4 or the C6 atom inhibit, both isozymes, whereas a bulkier substituent such as a carbamate is, tolerated only at the C4 position. The 1.7 A crystal structure of MAO B in, complex with, 4-(N-methyl-N-ethyl-carbamoyloxy)-N-methyl-N-propargyl-1(R)-aminoindan, shows that the binding mode is similar to that of rasagiline with the, carbamate moiety occupying the entrance cavity space. 1(R)-Aminoindan, the, major metabolic product of rasagiline, and its analogues reversibly, inhibit both MAO A and MAO B. The crystal structure of, N-methyl-1(R)-aminoindan bound to MAO B shows that its aminoindan ring, adopts a different orientation compared to that of rasagiline. | ||
==About this Structure== | ==About this Structure== | ||
2C65 is a | 2C65 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with FAD as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Amine_oxidase_(flavin-containing) Amine oxidase (flavin-containing)], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.4.3.4 1.4.3.4] Structure known Active Site: AC1. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=2C65 OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: transmembrane]] | [[Category: transmembrane]] | ||
''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on | ''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 5 13:16:51 2007'' | ||
Revision as of 14:11, 5 November 2007
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MAO INHIBITION BY RASAGILINE ANALOGUES
OverviewOverview
Monoamine oxidases A and B (MAO A and B) catalyze the degradation of, neurotransmitters and represent drug targets for the treatment of, neurodegenerative disorders. Rasagiline is an irreversible, MAO, B-selective inhibitor that has been approved as a novel anti-Parkinson's, drug. In this study, we investigate the inhibition of recombinant human, MAO A and MAO B by several rasagiline analogues. Different substituents, added onto the rasagiline scaffold alter the binding affinity depending on, the position on the aminoindan ring and on the size of the substituent., Compounds with a hydroxyl group on either the C4 or the C6 atom inhibit, both isozymes, whereas a bulkier substituent such as a carbamate is, tolerated only at the C4 position. The 1.7 A crystal structure of MAO B in, complex with, 4-(N-methyl-N-ethyl-carbamoyloxy)-N-methyl-N-propargyl-1(R)-aminoindan, shows that the binding mode is similar to that of rasagiline with the, carbamate moiety occupying the entrance cavity space. 1(R)-Aminoindan, the, major metabolic product of rasagiline, and its analogues reversibly, inhibit both MAO A and MAO B. The crystal structure of, N-methyl-1(R)-aminoindan bound to MAO B shows that its aminoindan ring, adopts a different orientation compared to that of rasagiline.
About this StructureAbout this Structure
2C65 is a Single protein structure of sequence from Homo sapiens with FAD as ligand. Active as Amine oxidase (flavin-containing), with EC number 1.4.3.4 Structure known Active Site: AC1. Full crystallographic information is available from OCA.
ReferenceReference
Binding of rasagiline-related inhibitors to human monoamine oxidases: a kinetic and crystallographic analysis., Binda C, Hubalek F, Li M, Herzig Y, Sterling J, Edmondson DE, Mattevi A, J Med Chem. 2005 Dec 29;48(26):8148-54. PMID:16366596
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OCA- Pages with broken file links
- Amine oxidase (flavin-containing)
- Homo sapiens
- Single protein
- Binda, C.
- Edmondson, D.E.
- Herzig, Y.
- Hubalek, F.
- Li, M.
- Mattevi, A.
- Sterling, J.
- FAD
- Acetylation
- Enantioselectivity
- Fad
- Flavin
- Flavoprotein
- Human monoamine oxidase
- Inhibitor binding
- Mitochondrion
- Oxidoreductase
- Parkinson
- Rasagiline
- Transmembrane