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| | <StructureSection load='2bk3' size='340' side='right'caption='[[2bk3]], [[Resolution|resolution]] 1.80Å' scene=''> | | <StructureSection load='2bk3' size='340' side='right'caption='[[2bk3]], [[Resolution|resolution]] 1.80Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2bk3]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2BK3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2BK3 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2bk3]] 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=2BK3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2BK3 FirstGlance]. <br> |
| - | </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=FOF:(2E,6E)-3,7,11-trimethyldodeca-2,6,10-trien-1-ol'>FOF</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.8Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1gos|1gos]], [[1h8r|1h8r]], [[1oj9|1oj9]], [[1oja|1oja]], [[1ojb|1ojb]], [[1ojc|1ojc]], [[1ojd|1ojd]], [[1s2q|1s2q]], [[1s2y|1s2y]], [[1s3b|1s3b]], [[1s3e|1s3e]], [[2bk4|2bk4]], [[2bk5|2bk5]]</div></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=FOF:(2E,6E)-3,7,11-trimethyldodeca-2,6,10-trien-1-ol'>FOF</scene></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Monoamine_oxidase Monoamine oxidase], with EC number [https://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'>[https://proteopedia.org/fgij/fg.htm?mol=2bk3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2bk3 OCA], [https://pdbe.org/2bk3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2bk3 RCSB], [https://www.ebi.ac.uk/pdbsum/2bk3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2bk3 ProSAT]</span></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=2bk3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2bk3 OCA], [https://pdbe.org/2bk3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2bk3 RCSB], [https://www.ebi.ac.uk/pdbsum/2bk3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2bk3 ProSAT]</span></td></tr> |
| | </table> | | </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 == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Monoamine oxidase]]
| + | [[Category: Binda C]] |
| - | [[Category: Binda, C]] | + | [[Category: Edmondson DE]] |
| - | [[Category: Edmondson, D E]] | + | [[Category: Mattevi A]] |
| - | [[Category: Mattevi, A]] | + | |
| - | [[Category: Acetylation]]
| + | |
| - | [[Category: Fad]]
| + | |
| - | [[Category: Fad-containing amine oxidase]]
| + | |
| - | [[Category: Farnesol]]
| + | |
| - | [[Category: Flavoprotein]]
| + | |
| - | [[Category: Maob]]
| + | |
| - | [[Category: Mitochondrion]]
| + | |
| - | [[Category: Oxidoreductase]]
| + | |
| - | [[Category: Transmembrane]]
| + | |
| Structural highlights
Function
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
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Several reversible inhibitors selective for human monoamine oxidase B (MAO B) that do not inhibit MAO A have been described in the literature. The following compounds: 8-(3-chlorostyryl)caffeine, 1,4-diphenyl-2-butene, and trans,trans-farnesol are shown to inhibit competitively human, horse, rat, and mouse MAO B with K(i) values in the low micromolar range but are without effect on either bovine or sheep MAO B or human MAO A. In contrast, the reversible competitive inhibitor isatin binds to all known MAO B and MAO A with similar affinities. Sequence alignments and the crystal structures of human MAO B in complex with 1,4-diphenyl-2-butene or with trans,trans-farnesol provide molecular insights into these specificities. These inhibitors span the substrate and entrance cavities with the side chain of Ile-199 rotated out of its normal conformation suggesting that Ile-199 is gating the substrate cavity. Ile-199 is conserved in all known MAO B sequences except bovine MAO B, which has Phe in this position (the sequence of sheep MAO B is unknown). Phe is conserved in the analogous position in MAO A sequences. The human MAO B I199F mutant protein of MAO B binds to isatin (K(i) = 3 microM) but not to the three inhibitors listed above. The crystal structure of this mutant demonstrates that the side chain of Phe-199 interferes with the binding of those compounds. This suggests that the Ile-199 "gate" is a determinant for the specificity of these MAO B inhibitors and provides a molecular basis for the development of MAO B-specific reversible inhibitors without interference with MAO A function in neurotransmitter metabolism.
Demonstration of isoleucine 199 as a structural determinant for the selective inhibition of human monoamine oxidase B by specific reversible inhibitors.,Hubalek F, Binda C, Khalil A, Li M, Mattevi A, Castagnoli N, Edmondson DE J Biol Chem. 2005 Apr 22;280(16):15761-6. Epub 2005 Feb 14. PMID:15710600[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Hubalek F, Binda C, Khalil A, Li M, Mattevi A, Castagnoli N, Edmondson DE. Demonstration of isoleucine 199 as a structural determinant for the selective inhibition of human monoamine oxidase B by specific reversible inhibitors. J Biol Chem. 2005 Apr 22;280(16):15761-6. Epub 2005 Feb 14. PMID:15710600 doi:10.1074/jbc.M500949200
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