2c66: Difference between revisions
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==MAO | |||
==MAO inhibition by rasagiline analogues== | |||
<StructureSection load='2c66' size='340' side='right' caption='[[2c66]], [[Resolution|resolution]] 2.50Å' scene=''> | <StructureSection load='2c66' size='340' side='right' caption='[[2c66]], [[Resolution|resolution]] 2.50Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
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<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1gos|1gos]], [[1h8r|1h8r]], [[1oj9|1oj9]], [[1oja|1oja]], [[1ojb|1ojb]], [[1ojc|1ojc]], [[1ojd|1ojd]], [[1s2q|1s2q]], [[1s2y|1s2y]], [[1s3b|1s3b]], [[1s3e|1s3e]], [[2bk3|2bk3]], [[2bk4|2bk4]], [[2bk5|2bk5]], [[2byb|2byb]], [[2c65|2c65]], [[2c64|2c64]], [[2c67|2c67]]</td></tr> | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1gos|1gos]], [[1h8r|1h8r]], [[1oj9|1oj9]], [[1oja|1oja]], [[1ojb|1ojb]], [[1ojc|1ojc]], [[1ojd|1ojd]], [[1s2q|1s2q]], [[1s2y|1s2y]], [[1s3b|1s3b]], [[1s3e|1s3e]], [[2bk3|2bk3]], [[2bk4|2bk4]], [[2bk5|2bk5]], [[2byb|2byb]], [[2c65|2c65]], [[2c64|2c64]], [[2c67|2c67]]</td></tr> | ||
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Monoamine_oxidase Monoamine oxidase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.4.3.4 1.4.3.4] </span></td></tr> | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Monoamine_oxidase Monoamine oxidase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.4.3.4 1.4.3.4] </span></td></tr> | ||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2c66 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2c66 OCA], [http://pdbe.org/2c66 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2c66 RCSB], [http://www.ebi.ac.uk/pdbsum/2c66 PDBsum]</span></td></tr> | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2c66 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2c66 OCA], [http://pdbe.org/2c66 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2c66 RCSB], [http://www.ebi.ac.uk/pdbsum/2c66 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2c66 ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Evolutionary Conservation == | == Evolutionary Conservation == | ||
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Check<jmol> | Check<jmol> | ||
<jmolCheckbox> | <jmolCheckbox> | ||
<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/c6/2c66_consurf.spt"</scriptWhenChecked> | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/c6/2c66_consurf.spt"</scriptWhenChecked> | ||
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | ||
<text>to colour the structure by Evolutionary Conservation</text> | <text>to colour the structure by Evolutionary Conservation</text> | ||
Revision as of 11:46, 23 May 2018
MAO inhibition by rasagiline analoguesMAO inhibition by rasagiline analogues
Structural highlights
Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedMonoamine 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. 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[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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