1sii: Difference between revisions

Revision as of 08:44, 3 May 2008

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

OverviewOverview

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.

About this StructureAbout this Structure

1SII is a Single protein structure of sequence from Arthrobacter globiformis. Full crystallographic information is available from OCA.

ReferenceReference

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:15323556 Page seeded by OCA on Sat May 3 08:44:44 2008

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OCA

@@ Line 1: / Line 1: @@
 [[Image:1sii.gif|left|200px]]
- {{Structure
+<!--
-|PDB= 1sii |SIZE=350|CAPTION= <scene name='initialview01'>1sii</scene>, resolution 1.70&Aring;
+The line below this paragraph, containing "STRUCTURE_1sii", creates the "Structure Box" on the page.
-|SITE=
+You may change the PDB parameter (which sets the PDB file loaded into the applet)
-|LIGAND= <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>
+or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
-|ACTIVITY= <span class='plainlinks'>[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] </span>
+or leave the SCENE parameter empty for the default display.
-|GENE= ATCC8010, IFO12137 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1665 Arthrobacter globiformis])
+-->
-|DOMAIN=
+{{STRUCTURE_1sii|  PDB=1sii  |  SCENE=  }}
-|RELATEDENTRY=[[1av4|1AV4]], [[1sih|1SIH]]
-|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1sii FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1sii OCA], [http://www.ebi.ac.uk/pdbsum/1sii PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1sii RCSB]</span>
-}}
 '''AGAO in covalent complex with the inhibitor NOBA ("4-(2-naphthyloxy)-2-butyn-1-amine")'''
@@ Line 23: / Line 20: @@
 ==Reference==
 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://www.ncbi.nlm.nih.gov/pubmed/15323556 15323556]
-[[Category: Amine oxidase (copper-containing)]]
 [[Category: Arthrobacter globiformis]]
 [[Category: Single protein]]
@@ Line 29: / Line 25: @@
 [[Category: Guss, J M.]]
 [[Category: Langley, D B.]]
-[[Category: 4-(2-naphthyloxy)-2-butyn-1-amine]]
+[[Category: Amine oxidase]]
-[[Category: 4-(aryloxy)-2-butynamine]]
+[[Category: Cao]]
-[[Category: amine oxidase]]
+[[Category: Copper-containing]]
-[[Category: cao]]
+[[Category: Cuao]]
-[[Category: copper-containing]]
+[[Category: Noba]]
-[[Category: cuao]]
+[[Category: Quinone]]
-[[Category: noba]]
+[[Category: Suicide inhibition]]
-[[Category: quinone]]
+[[Category: Tpq]]
-[[Category: suicide inhibition]]
+[[Category: Trihydroxyphenylalanine quinone]]
-[[Category: tpq]]
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May  3 08:44:44 2008''
-[[Category: trihydroxyphenylalanine quinone]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 23:42:29 2008''