1o5w
From Proteopedia
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| - | [[Image:1o5w.jpg|left|200px]]<br /><applet load="1o5w" size="350" color="white" frame="true" align="right" spinBox="true" | ||
| - | caption="1o5w, resolution 3.20Å" /> | ||
| - | '''The structure basis of specific recognitions for substrates and inhibitors of rat monoamine oxidase A'''<br /> | ||
| - | == | + | ==The structure basis of specific recognitions for substrates and inhibitors of rat monoamine oxidase A== |
| + | <StructureSection load='1o5w' size='340' side='right'caption='[[1o5w]], [[Resolution|resolution]] 3.20Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[1o5w]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1O5W OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1O5W 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]] 3.2Å</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=MLG:N-[3-(2,4-DICHLOROPHENOXY)PROPYL]-N-METHYL-N-PROP-2-YNYLAMINE'>MLG</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=1o5w FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1o5w OCA], [https://pdbe.org/1o5w PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1o5w RCSB], [https://www.ebi.ac.uk/pdbsum/1o5w PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1o5w ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/AOFA_RAT AOFA_RAT] 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. MAOA preferentially oxidizes biogenic amines such as 5-hydroxytryptamine (5-HT), norepinephrine and epinephrine. | ||
| + | == 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/o5/1o5w_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=1o5w ConSurf]. | ||
| + | <div style="clear:both"></div> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
Monoamine oxidase (MAO), a mitochondrial outer membrane enzyme, catalyzes the degradation of neurotransmitters in the central nervous system and is the target for anti-depression drug design. Two subtypes of MAO, MAOA and MAOB, are similar in primary sequences but have unique substrate and inhibitor specificities. The structures of human MAOB complexed with various inhibitors were reported early. To understand the mechanisms of specific substrate and inhibitor recognitions of MAOA and MAOB, we have determined the crystal structure of rat MAOA complexed with the specific inhibitor, clorgyline, at 3.2A resolution. The comparison of the structures between MAOA and MAOB clearly explains the specificity of clorgyline for MAOA inhibition. The fitting of serotonin into the binding pockets of MAOs demonstrates that MAOB Tyr326 would block access of the 5-hydroxy group of serotonin into the enzyme. These results will lead to further understanding of the MAOA function and to new anti-depression drug design. This study also presents that MAOA has a transmembrane helix at the C-terminal region. This is the first crystal structure of membrane protein with an isolated transmembrane helix. | Monoamine oxidase (MAO), a mitochondrial outer membrane enzyme, catalyzes the degradation of neurotransmitters in the central nervous system and is the target for anti-depression drug design. Two subtypes of MAO, MAOA and MAOB, are similar in primary sequences but have unique substrate and inhibitor specificities. The structures of human MAOB complexed with various inhibitors were reported early. To understand the mechanisms of specific substrate and inhibitor recognitions of MAOA and MAOB, we have determined the crystal structure of rat MAOA complexed with the specific inhibitor, clorgyline, at 3.2A resolution. The comparison of the structures between MAOA and MAOB clearly explains the specificity of clorgyline for MAOA inhibition. The fitting of serotonin into the binding pockets of MAOs demonstrates that MAOB Tyr326 would block access of the 5-hydroxy group of serotonin into the enzyme. These results will lead to further understanding of the MAOA function and to new anti-depression drug design. This study also presents that MAOA has a transmembrane helix at the C-terminal region. This is the first crystal structure of membrane protein with an isolated transmembrane helix. | ||
| - | + | Structure of rat monoamine oxidase A and its specific recognitions for substrates and inhibitors.,Ma J, Yoshimura M, Yamashita E, Nakagawa A, Ito A, Tsukihara T J Mol Biol. 2004 Apr 16;338(1):103-14. PMID:15050826<ref>PMID:15050826</ref> | |
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| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | + | </div> | |
| - | + | <div class="pdbe-citations 1o5w" style="background-color:#fffaf0;"></div> | |
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| - | + | ==See Also== | |
| + | *[[Monoamine oxidase|Monoamine oxidase]] | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Rattus norvegicus]] | ||
| + | [[Category: Ito A]] | ||
| + | [[Category: Ma J]] | ||
| + | [[Category: Nakagawa A]] | ||
| + | [[Category: Tsukihara T]] | ||
| + | [[Category: Yamashita E]] | ||
| + | [[Category: Yoshimura M]] | ||
Current revision
The structure basis of specific recognitions for substrates and inhibitors of rat monoamine oxidase A
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