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1sih

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

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Retrieved from "http://52.214.119.220/wiki/index.php/1sih"

Categories: Arthrobacter globiformis | Large Structures | Duff AP | Guss JM | Langley DB

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-[[Image:1sih.gif|left|200px]]<br /><applet load="1sih" size="450" color="white" frame="true" align="right" spinBox="true"
-caption="1sih, resolution 1.73&Aring;" />
-'''AGAO in covalent complex with the inhibitor MOBA ("4-(4-methylphenoxy)-2-butyn-1-amine")'''<br />
-==Overview==
+==AGAO in covalent complex with the inhibitor MOBA ("4-(4-methylphenoxy)-2-butyn-1-amine")==
-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.
+<StructureSection load='1sih' size='340' side='right'caption='[[1sih]], [[Resolution|resolution]] 1.73&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[1sih]] 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=1SIH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1SIH 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]] 1.73&#8491;</td></tr>
+<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=MBQ:2-HYDROXY-5-({1-[(4-METHYLPHENOXY)METHYL]-3-OXOPROP-1-ENYL}AMINO)-L-TYROSINE'>MBQ</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=1sih FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1sih OCA], [https://pdbe.org/1sih PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1sih RCSB], [https://www.ebi.ac.uk/pdbsum/1sih PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1sih ProSAT]</span></td></tr>
+</table>
+== Function ==
+[https://www.uniprot.org/uniprot/PAOX_ARTGO PAOX_ARTGO]
+== 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/si/1sih_consurf.spt"</scriptWhenChecked>
+    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.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=1sih ConSurf].
+<div style="clear:both"></div>
-==About this Structure==
+==See Also==
-SIH 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 SO4, CU, NA and GOL 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://ispc.weizmann.ac.il/oca-bin/ocashort?id=1SIH OCA].
+*[[Copper amine oxidase 3D structures|Copper amine oxidase 3D structures]]
+__TOC__
-==Reference==
+</StructureSection>
-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]
-[[Category: Amine oxidase (copper-containing)]]
 [[Category: Arthrobacter globiformis]]
-[[Category: Single protein]]
+[[Category: Large Structures]]
-[[Category: Duff, A.P.]]
+[[Category: Duff AP]]
-[[Category: Guss, J.M.]]
+[[Category: Guss JM]]
-[[Category: Langley, D.B.]]
+[[Category: Langley DB]]
-[[Category: CU]]
-[[Category: GOL]]
-[[Category: NA]]
-[[Category: SO4]]
-[[Category: 4-(4-methylphenoxyoxy)-2-butyn-1-amine]]
-[[Category: 4-(aryloxy)-2-butynamine]]
-[[Category: amine oxidase]]
-[[Category: cao]]
-[[Category: copper-containing]]
-[[Category: cuao]]
-[[Category: moba]]
-[[Category: quinone]]
-[[Category: suicide inhibition]]
-[[Category: tpq]]
-[[Category: trihydroxyphenylalanine quinone]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Wed Nov 21 02:24:22 2007''

1sih

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

Structural highlights

Function

Evolutionary Conservation

See Also

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