1sii: Difference between revisions
No edit summary |
No edit summary |
||
| Line 1: | Line 1: | ||
[[Image:1sii.gif|left|200px]] | [[Image:1sii.gif|left|200px]] | ||
'''AGAO in covalent complex with the inhibitor NOBA ("4-(2-naphthyloxy)-2-butyn-1-amine")''' | {{Structure | ||
|PDB= 1sii |SIZE=350|CAPTION= <scene name='initialview01'>1sii</scene>, resolution 1.70Å | |||
|SITE= | |||
|LIGAND= <scene name='pdbligand=CU:COPPER+(II)+ION'>CU</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene> and <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene> | |||
|ACTIVITY= [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] | |||
|GENE= ATCC8010, IFO12137 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1665 Arthrobacter globiformis]) | |||
}} | |||
'''AGAO in covalent complex with the inhibitor NOBA ("4-(2-naphthyloxy)-2-butyn-1-amine")''' | |||
==Overview== | ==Overview== | ||
| Line 7: | Line 16: | ||
==About this Structure== | ==About this Structure== | ||
1SII is a [ | 1SII is a [[Single protein]] structure of sequence from [http://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]. | ||
==Reference== | ==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:// | 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: Amine oxidase (copper-containing)]] | ||
[[Category: Arthrobacter globiformis]] | [[Category: Arthrobacter globiformis]] | ||
| Line 33: | Line 42: | ||
[[Category: trihydroxyphenylalanine quinone]] | [[Category: trihydroxyphenylalanine quinone]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 14:05:24 2008'' | ||
Revision as of 15:05, 20 March 2008
| |||||||
| , resolution 1.70Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | , , and | ||||||
| Gene: | ATCC8010, IFO12137 (Arthrobacter globiformis) | ||||||
| Activity: | Amine oxidase (copper-containing), with EC number 1.4.3.6 | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
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 Thu Mar 20 14:05:24 2008