2c67: Difference between revisions

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[[Image:2c67.gif|left|200px]]
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{{STRUCTURE_2c67|  PDB=2c67  |  SCENE=  }}
'''MAO INHIBITION BY RASAGILINE ANALOGUES'''


==MAO inhibition by rasagiline analogues==
<StructureSection load='2c67' size='340' side='right'caption='[[2c67]], [[Resolution|resolution]] 1.70&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2c67]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2C67 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2C67 FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.7&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FAD:FLAVIN-ADENINE+DINUCLEOTIDE'>FAD</scene>, <scene name='pdbligand=RM1:N-METHYL-1(R)-AMINOINDAN'>RM1</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2c67 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2c67 OCA], [https://pdbe.org/2c67 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2c67 RCSB], [https://www.ebi.ac.uk/pdbsum/2c67 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2c67 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/AOFB_HUMAN AOFB_HUMAN] Catalyzes the oxidative deamination of biogenic and xenobiotic amines and has important functions in the metabolism of neuroactive and vasoactive amines in the central nervous system and peripheral tissues. MAOB preferentially degrades benzylamine and phenylethylamine.
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/c6/2c67_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2c67 ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
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.


==Overview==
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<ref>PMID:16366596</ref>
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==
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
2C67 is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2C67 OCA].
</div>
<div class="pdbe-citations 2c67" style="background-color:#fffaf0;"></div>


==Reference==
==See Also==
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:[http://www.ncbi.nlm.nih.gov/pubmed/16366596 16366596]
*[[Monoamine oxidase|Monoamine oxidase]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Single protein]]
[[Category: Large Structures]]
[[Category: Binda, C.]]
[[Category: Binda C]]
[[Category: Edmondson, D E.]]
[[Category: Edmondson DE]]
[[Category: Herzig, Y.]]
[[Category: Herzig Y]]
[[Category: Hubalek, F.]]
[[Category: Hubalek F]]
[[Category: Li, M.]]
[[Category: Li M]]
[[Category: Mattevi, A.]]
[[Category: Mattevi A]]
[[Category: Sterling, J.]]
[[Category: Sterling J]]
[[Category: Enantioselectivity]]
[[Category: Fad]]
[[Category: Flavin]]
[[Category: Flavoprotein]]
[[Category: Human monoamine oxidase]]
[[Category: Inhibitor binding]]
[[Category: Mitochondrion]]
[[Category: Oxidoreductase]]
[[Category: Parkinson]]
[[Category: Rasagiline]]
[[Category: Transmembrane]]
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