2pnc

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{{STRUCTURE_2pnc| PDB=2pnc | SCENE= }}
{{STRUCTURE_2pnc| PDB=2pnc | SCENE= }}
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'''Crystal Structure of Bovine Plasma Copper-Containing Amine Oxidase in Complex with Clonidine'''
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===Crystal Structure of Bovine Plasma Copper-Containing Amine Oxidase in Complex with Clonidine===
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==Overview==
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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.
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(as it appears on PubMed at http://www.pubmed.gov), where 17989349 is the PubMed ID number.
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{{ABSTRACT_PUBMED_17989349}}
==About this Structure==
==About this Structure==
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==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://www.ncbi.nlm.nih.gov/pubmed/17989349 17989349]
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]
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Crystal structure of amine oxidase from bovine serum., Lunelli M, Di Paolo ML, Biadene M, Calderone V, Battistutta R, Scarpa M, Rigo A, Zanotti G, J Mol Biol. 2005 Mar 4;346(4):991-1004. Epub 2005 Jan 25. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/15701511 15701511]
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Crystallization and preliminary X-ray data of amine oxidase from bovine serum., Calderone V, Di Paolo ML, Trabucco M, Biadene M, Battistutta R, Rigo A, Zanotti G, Acta Crystallogr D Biol Crystallogr. 2003 Apr;59(Pt 4):727-9. Epub 2003, Mar 25. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/12657794 12657794]
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Crystal structure of a quinoenzyme: copper amine oxidase of Escherichia coli at 2 A resolution., Parsons MR, Convery MA, Wilmot CM, Yadav KD, Blakeley V, Corner AS, Phillips SE, McPherson MJ, Knowles PF, Structure. 1995 Nov 15;3(11):1171-84. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/8591028 8591028]
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Crystal structure of a eukaryotic (pea seedling) copper-containing amine oxidase at 2.2 A resolution., Kumar V, Dooley DM, Freeman HC, Guss JM, Harvey I, McGuirl MA, Wilce MC, Zubak VM, Structure. 1996 Aug 15;4(8):943-55. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/8805580 8805580]
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The crystal structure of Pichia pastoris lysyl oxidase., Duff AP, Cohen AE, Ellis PJ, Kuchar JA, Langley DB, Shepard EM, Dooley DM, Freeman HC, Guss JM, Biochemistry. 2003 Dec 30;42(51):15148-57. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/14690425 14690425]
[[Category: Bos taurus]]
[[Category: Bos taurus]]
[[Category: Single protein]]
[[Category: Single protein]]
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[[Category: Quinoenzyme]]
[[Category: Quinoenzyme]]
[[Category: Tpq]]
[[Category: Tpq]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jul 28 16:41:27 2008''

Revision as of 13:41, 28 July 2008

Template:STRUCTURE 2pnc

Crystal Structure of Bovine Plasma Copper-Containing Amine Oxidase in Complex with Clonidine

Template:ABSTRACT PUBMED 17989349

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

Crystal structure of amine oxidase from bovine serum., Lunelli M, Di Paolo ML, Biadene M, Calderone V, Battistutta R, Scarpa M, Rigo A, Zanotti G, J Mol Biol. 2005 Mar 4;346(4):991-1004. Epub 2005 Jan 25. PMID:15701511

Crystallization and preliminary X-ray data of amine oxidase from bovine serum., Calderone V, Di Paolo ML, Trabucco M, Biadene M, Battistutta R, Rigo A, Zanotti G, Acta Crystallogr D Biol Crystallogr. 2003 Apr;59(Pt 4):727-9. Epub 2003, Mar 25. PMID:12657794

Crystal structure of a quinoenzyme: copper amine oxidase of Escherichia coli at 2 A resolution., Parsons MR, Convery MA, Wilmot CM, Yadav KD, Blakeley V, Corner AS, Phillips SE, McPherson MJ, Knowles PF, Structure. 1995 Nov 15;3(11):1171-84. PMID:8591028

Crystal structure of a eukaryotic (pea seedling) copper-containing amine oxidase at 2.2 A resolution., Kumar V, Dooley DM, Freeman HC, Guss JM, Harvey I, McGuirl MA, Wilce MC, Zubak VM, Structure. 1996 Aug 15;4(8):943-55. PMID:8805580

The crystal structure of Pichia pastoris lysyl oxidase., Duff AP, Cohen AE, Ellis PJ, Kuchar JA, Langley DB, Shepard EM, Dooley DM, Freeman HC, Guss JM, Biochemistry. 2003 Dec 30;42(51):15148-57. PMID:14690425

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