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1sii

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[[Image:1sii.gif|left|200px]]<br /><applet load="1sii" size="350" color="white" frame="true" align="right" spinBox="true"
 
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caption="1sii, resolution 1.70&Aring;" />
 
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'''AGAO in covalent complex with the inhibitor NOBA ("4-(2-naphthyloxy)-2-butyn-1-amine")'''<br />
 
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==Overview==
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==AGAO in covalent complex with the inhibitor NOBA ("4-(2-naphthyloxy)-2-butyn-1-amine")==
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A series of compounds derived from a previously identified substrate analogue of copper amine oxidases (CuAOs) (Shepard et al. (2002) Eur. J. Biochem. 269, 3645-3658) has been screened against six different CuAOs with a view to designing potent and selective inhibitors. The substrate analogues investigated were 4-(1-naphthyloxy)-2-butyn-1-amine, 4-(2-methylphenoxy)-2-butyn-1-amine, 4-(3-methylphenoxy)-2-butyn-1-amine, 4-(4-methylphenoxy)-2-butyn-1-amine, and 4-phenoxy-2-butyn-1-amine. These compounds were screened against equine plasma amine oxidase (EPAO), Pisum sativum amine oxidase (PSAO), Pichia pastoris lysyl oxidase (PPLO), bovine plasma amine oxidase (BPAO), human kidney diamine oxidase (KDAO), and Arthrobacter globiformis amine oxidase (AGAO) to examine the effect of different substituent groups on potency. Despite the similar structures of the 4-aryloxy analogues evaluated, striking differences in potency were observed. In addition, crystal structures of AGAO derivitized with 4-(2-naphthyloxy)-2-butyn-1-amine and 4-(4-methylphenoxy)-2-butyn-1-amine were obtained at a resolution of 1.7 A. The structures reveal a novel and unprecedented reaction mechanism involving covalent attachment of the alpha,beta-unsaturated aldehyde turnover product to the amino group of the reduced 2,4,5-trihydroxyphenylalanine quinone (TPQ) cofactor. Collectively, the structural and inhibition results support the feasibility of designing selective mechanism-based inhibitors of copper amine oxidases.
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<StructureSection load='1sii' size='340' side='right'caption='[[1sii]], [[Resolution|resolution]] 1.70&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[1sii]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Arthrobacter_globiformis Arthrobacter globiformis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1SII OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1SII FirstGlance]. <br>
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</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>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CU:COPPER+(II)+ION'>CU</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=NBQ:2-HYDROXY-5-({1-[(2-NAPHTHYLOXY)METHYL]-3-OXOPROP-1-ENYL}AMINO)TYROSINE'>NBQ</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1sii FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1sii OCA], [https://pdbe.org/1sii PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1sii RCSB], [https://www.ebi.ac.uk/pdbsum/1sii PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1sii ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/PAOX_ARTGO PAOX_ARTGO]
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/si/1sii_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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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=1sii ConSurf].
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<div style="clear:both"></div>
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==About this Structure==
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==See Also==
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1SII is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Arthrobacter_globiformis Arthrobacter globiformis] with <scene name='pdbligand=CU:'>CU</scene>, <scene name='pdbligand=NA:'>NA</scene>, <scene name='pdbligand=SO4:'>SO4</scene> and <scene name='pdbligand=GOL:'>GOL</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Amine_oxidase_(copper-containing) Amine oxidase (copper-containing)], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.4.3.6 1.4.3.6] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1SII OCA].
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*[[Copper amine oxidase 3D structures|Copper amine oxidase 3D structures]]
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__TOC__
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==Reference==
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</StructureSection>
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Differential inhibition of six copper amine oxidases by a family of 4-(aryloxy)-2-butynamines: evidence for a new mode of inactivation., O'Connell KM, Langley DB, Shepard EM, Duff AP, Jeon HB, Sun G, Freeman HC, Guss JM, Sayre LM, Dooley DM, Biochemistry. 2004 Aug 31;43(34):10965-78. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=15323556 15323556]
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[[Category: Amine oxidase (copper-containing)]]
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[[Category: Arthrobacter globiformis]]
[[Category: Arthrobacter globiformis]]
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[[Category: Single protein]]
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[[Category: Large Structures]]
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[[Category: Duff, A P.]]
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[[Category: Duff AP]]
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[[Category: Guss, J M.]]
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[[Category: Guss JM]]
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[[Category: Langley, D B.]]
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[[Category: Langley DB]]
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[[Category: CU]]
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[[Category: GOL]]
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[[Category: NA]]
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[[Category: SO4]]
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[[Category: 4-(2-naphthyloxy)-2-butyn-1-amine]]
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[[Category: 4-(aryloxy)-2-butynamine]]
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[[Category: amine oxidase]]
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[[Category: cao]]
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[[Category: copper-containing]]
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[[Category: cuao]]
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[[Category: noba]]
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[[Category: quinone]]
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[[Category: suicide inhibition]]
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[[Category: tpq]]
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[[Category: trihydroxyphenylalanine quinone]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:01:50 2008''
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Current revision

AGAO in covalent complex with the inhibitor NOBA ("4-(2-naphthyloxy)-2-butyn-1-amine")

PDB ID 1sii

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