1oj9: Difference between revisions

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<StructureSection load='1oj9' size='340' side='right'caption='[[1oj9]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
<StructureSection load='1oj9' size='340' side='right'caption='[[1oj9]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[1oj9]] 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=1OJ9 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1OJ9 FirstGlance]. <br>
<table><tr><td colspan='2'>[[1oj9]] 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=1OJ9 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1OJ9 FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=1PB:1,4-DIPHENYL-2-BUTENE'>1PB</scene>, <scene name='pdbligand=FAD:FLAVIN-ADENINE+DINUCLEOTIDE'>FAD</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]] 2.3&#8491;</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]], [[1ojb|1ojb]], [[1oja|1oja]], [[1ojc|1ojc]], [[1ojd|1ojd]]</div></td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=1PB:1,4-DIPHENYL-2-BUTENE'>1PB</scene>, <scene name='pdbligand=FAD:FLAVIN-ADENINE+DINUCLEOTIDE'>FAD</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=1oj9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1oj9 OCA], [https://pdbe.org/1oj9 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1oj9 RCSB], [https://www.ebi.ac.uk/pdbsum/1oj9 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1oj9 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=1oj9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1oj9 OCA], [https://pdbe.org/1oj9 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1oj9 RCSB], [https://www.ebi.ac.uk/pdbsum/1oj9 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1oj9 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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</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=1oj9 ConSurf].
</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=1oj9 ConSurf].
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<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Monoamine oxidase B (MAO-B) is an outer mitochondrial membrane-bound enzyme that catalyzes the oxidative deamination of arylalkylamine neurotransmitters and has been a target for a number of clinically used drug inhibitors. The 1.7-A structure of the reversible isatin-MAO-B complex has been determined; it forms a basis for the interpretation of the enzyme's structure when bound to either reversible or irreversible inhibitors. 1,4-Diphenyl-2-butene is found to be a reversible MAO-B inhibitor, which occupies both the entrance and substrate cavity space in the enzyme. Comparison of these two structures identifies Ile-199 as a "gate" between the two cavities. Rotation of the side chain allows for either separation or fusion of the two cavities. Inhibition of the enzyme with N-(2-aminoethyl)-p-chlorobenzamide results in the formation of a covalent N(5) flavin adduct with the phenyl ring of the inhibitor occupying a position in the catalytic site overlapping that of isatin. Inhibition of MAO-B with the clinically used trans-2-phenylcyclopropylamine results in the formation of a covalent C(4a) flavin adduct with an opened cyclopropyl ring and the phenyl ring in a parallel orientation to the flavin. The peptide bond between the flavin-substituted Cys-397 and Tyr-398 is in a cis conformation, which allows the proper orientation of the phenolic ring of Tyr-398 in the active site. The flavin ring exists in a twisted nonplanar conformation, which is observed in the oxidized form as well as in both the N(5) and the C(4a) adducts. An immobile water molecule is H-bonded to Lys-296 and to the N(5) of the flavin as observed in other flavin-dependent amine oxidases. The active site cavities are highly apolar; however, hydrophilic areas exist near the flavin and direct the amine moiety of the substrate for binding and catalysis. Small conformational changes are observed on comparison of the different inhibitor-enzyme complexes. Future MAO-B drug design will need to consider "induced fit" contributions as an element in ligand-enzyme interactions.
Insights into the mode of inhibition of human mitochondrial monoamine oxidase B from high-resolution crystal structures.,Binda C, Li M, Hubalek F, Restelli N, Edmondson DE, Mattevi A Proc Natl Acad Sci U S A. 2003 Aug 19;100(17):9750-5. Epub 2003 Aug 11. PMID:12913124<ref>PMID:12913124</ref>
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 1oj9" style="background-color:#fffaf0;"></div>


==See Also==
==See Also==
*[[Monoamine oxidase|Monoamine oxidase]]
*[[Monoamine oxidase|Monoamine oxidase]]
== References ==
<references/>
__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: Fad-containing amine oxidase]]
[[Category: Maob]]
[[Category: Oxidoreductase]]
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