2pnc
From Proteopedia
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| - | [[Image:2pnc.jpg|left|200px]] | + | [[Image:2pnc.jpg|left|200px]] |
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| - | '''Crystal Structure of Bovine Plasma Copper-Containing Amine Oxidase in Complex with Clonidine''' | + | {{Structure |
| + | |PDB= 2pnc |SIZE=350|CAPTION= <scene name='initialview01'>2pnc</scene>, resolution 2.40Å | ||
| + | |SITE= <scene name='pdbsite=AC1:Nag+Binding+Site+For+Residue+D+800'>AC1</scene>, <scene name='pdbsite=AC2:Nag+Binding+Site+For+Residue+D+801'>AC2</scene>, <scene name='pdbsite=AC3:Nag+Binding+Site+For+Residue+E+800'>AC3</scene>, <scene name='pdbsite=AC4:Nag+Binding+Site+For+Residue+E+801'>AC4</scene>, <scene name='pdbsite=AC5:Nag+Binding+Site+For+Residue+E+802'>AC5</scene>, <scene name='pdbsite=AC6:Cu+Binding+Site+For+Residue+A+901'>AC6</scene>, <scene name='pdbsite=AC7:Cu+Binding+Site+For+Residue+B+901'>AC7</scene>, <scene name='pdbsite=AC8:Ca+Binding+Site+For+Residue+A+902'>AC8</scene>, <scene name='pdbsite=AC9:Ca+Binding+Site+For+Residue+A+903'>AC9</scene>, <scene name='pdbsite=BC1:Cl+Binding+Site+For+Residue+A+904'>BC1</scene>, <scene name='pdbsite=BC2:Ca+Binding+Site+For+Residue+B+905'>BC2</scene>, <scene name='pdbsite=BC3:Ca+Binding+Site+For+Residue+B+906'>BC3</scene>, <scene name='pdbsite=BC4:Cl+Binding+Site+For+Residue+B+907'>BC4</scene>, <scene name='pdbsite=BC5:Cl+Binding+Site+For+Residue+B+908'>BC5</scene>, <scene name='pdbsite=BC6:Clu+Binding+Site+For+Residue+A+1'>BC6</scene> and <scene name='pdbsite=BC7:Clu+Binding+Site+For+Residue+B+1'>BC7</scene> | ||
| + | |LIGAND= <scene name='pdbligand=CU:COPPER+(II)+ION'>CU</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene> and <scene name='pdbligand=CLU:'>CLU</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= | ||
| + | }} | ||
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| + | '''Crystal Structure of Bovine Plasma Copper-Containing Amine Oxidase in Complex with Clonidine''' | ||
| + | |||
==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 2PNC is a [ | + | 2PNC is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Bos_taurus Bos taurus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2PNC OCA]. |
==Reference== | ==Reference== | ||
| - | Multiple binding sites for substrates and modulators of semicarbazide-sensitive amine oxidases: kinetic consequences., Holt A, Smith DJ, Cendron L, Zanotti G, Rigo A, Di Paolo ML, Mol Pharmacol. 2008 Feb;73(2):525-38. Epub 2007 Nov 7. PMID:[http:// | + | Multiple binding sites for substrates and modulators of semicarbazide-sensitive amine oxidases: kinetic consequences., Holt A, Smith DJ, Cendron L, Zanotti G, Rigo A, Di Paolo ML, Mol Pharmacol. 2008 Feb;73(2):525-38. Epub 2007 Nov 7. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/17989349 17989349] |
[[Category: Amine oxidase (copper-containing)]] | [[Category: Amine oxidase (copper-containing)]] | ||
[[Category: Bos taurus]] | [[Category: Bos taurus]] | ||
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[[Category: tpq]] | [[Category: tpq]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 18:15:10 2008'' |
Revision as of 16:15, 20 March 2008
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| , resolution 2.40Å | |||||||
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| Sites: | , , , , , , , , , , , , , , and | ||||||
| Ligands: | , , and | ||||||
| Activity: | Amine oxidase (copper-containing), with EC number 1.4.3.6 | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Crystal Structure of Bovine Plasma Copper-Containing Amine Oxidase in Complex with Clonidine
Overview
Human semicarbazide-sensitive amine oxidase (SSAO) is a target for novel anti-inflammatory drugs that inhibit enzymatic activity. However, progress in developing such drugs has been hampered by an incomplete understanding of mechanisms involved in substrate turnover. We report here results of a comparative study of human and bovine SSAO enzymes that reveal binding of substrates and other ligands to at least two (human) and up to four (bovine) distinct sites on enzyme monomers. Anaerobic spectroscopy reveals binding of substrates (spermidine and benzylamine) and of an imidazoline site ligand (clonidine) to the reduced active site of bovine SSAO, whereas interactions with oxidized enzyme are evident in kinetic assays and crystallization studies. Radioligand binding experiments with [(3)H]tetraphenylphosphonium, an inhibitor of bovine SSAO that binds to an anionic cavity outside the active site, reveal competition with spermidine, benzylamine, and clonidine, indicating that these ligands also bind to this second anionic region. Kinetic models of bovine SSAO are consistent with one spermidine molecule straddling the active and secondary sites on both oxidized and reduced enzyme, whereas these sites are occupied by two individual molecules of smaller substrates such as benzylamine. Clonidine and other imidazoline site ligands enhance or inhibit activity as a result of differing affinities for both sites on oxidized and reduced enzyme. In contrast, although analyses of kinetic data obtained with human SSAO are also consistent with ligands binding to oxidized and reduced enzyme, we observed no apparent requirement for substrate or modulator binding to any secondary site to model enzyme behavior.
About this Structure
2PNC is a Single protein structure of sequence from Bos taurus. Full crystallographic information is available from OCA.
Reference
Multiple binding sites for substrates and modulators of semicarbazide-sensitive amine oxidases: kinetic consequences., Holt A, Smith DJ, Cendron L, Zanotti G, Rigo A, Di Paolo ML, Mol Pharmacol. 2008 Feb;73(2):525-38. Epub 2007 Nov 7. PMID:17989349
Page seeded by OCA on Thu Mar 20 18:15:10 2008
Categories: Amine oxidase (copper-containing) | Bos taurus | Single protein | Cendron, L. | Holt, A. | Paolo, M L.Di. | Rigo, A. | Smith, D J. | Zanotti, G. | CA | CL | CLU | CU | Amine oxidase | Clonidine | Copper | Oxidoreductase | Quinoenzyme | Tpq
