2c65: Difference between revisions

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Revision as of 02:17, 31 March 2008

File:2c65.gif

, resolution 1.70Å

Sites:

Ligands:

,

Activity:

Amine oxidase (flavin-containing), with EC number 1.4.3.4

Resources:

FirstGlance, OCA, PDBsum, RCSB

Coordinates:

save as pdb, mmCIF, xml

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. 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

Page seeded by OCA on Mon Mar 31 02:16:55 2008

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA

@@ Line 4: / Line 4: @@
 |PDB= 2c65 |SIZE=350|CAPTION= <scene name='initialview01'>2c65</scene>, resolution 1.70&Aring;
 |SITE= <scene name='pdbsite=AC1:4cr+Binding+Site+For+Chain+B'>AC1</scene>
-|LIGAND= <scene name='pdbligand=FAD:FLAVIN-ADENINE DINUCLEOTIDE'>FAD</scene>
+|LIGAND= <scene name='pdbligand=4CR:(1R)-4-({[ETHYL(METHYL)AMINO]CARBONYL}OXY)-N-METHYL-N-[(1E)-PROP-2-EN-1-YLIDENE]INDAN-1-AMINIUM'>4CR</scene>, <scene name='pdbligand=FAD:FLAVIN-ADENINE+DINUCLEOTIDE'>FAD</scene>
-|ACTIVITY= [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]
+|ACTIVITY= <span class='plainlinks'>[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] </span>
 |GENE=
+|DOMAIN=
+|RELATEDENTRY=
+|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2c65 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2c65 OCA], [http://www.ebi.ac.uk/pdbsum/2c65 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2c65 RCSB]</span>
 }}
@@ Line 30: / Line 33: @@
 [[Category: Mattevi, A.]]
 [[Category: Sterling, J.]]
-[[Category: FAD]]
 [[Category: acetylation]]
 [[Category: enantioselectivity]]
@@ Line 44: / Line 46: @@
 [[Category: transmembrane]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 16:11:17 2008''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 02:16:55 2008''