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| | ==Crystal Structure of Bovine Plasma Copper-Containing Amine Oxidase in Complex with Clonidine== | | ==Crystal Structure of Bovine Plasma Copper-Containing Amine Oxidase in Complex with Clonidine== |
| - | <StructureSection load='2pnc' size='340' side='right' caption='[[2pnc]], [[Resolution|resolution]] 2.40Å' scene=''> | + | <StructureSection load='2pnc' size='340' side='right'caption='[[2pnc]], [[Resolution|resolution]] 2.40Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2pnc]] is a 2 chain structure with 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]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2PNC FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2pnc]] is a 2 chain structure with sequence from [https://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]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2PNC FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=CLU:2,6-DICHLORO-N-IMIDAZOLIDIN-2-YLIDENEANILINE'>CLU</scene>, <scene name='pdbligand=CU:COPPER+(II)+ION'>CU</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.4Å</td></tr> |
| - | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=TPQ:5-(2-CARBOXY-2-AMINOETHYL)-2-HYDROXY-1,4-BENZOQUINONE'>TPQ</scene></td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=CLU:2,6-DICHLORO-N-IMIDAZOLIDIN-2-YLIDENEANILINE'>CLU</scene>, <scene name='pdbligand=CU:COPPER+(II)+ION'>CU</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=PRD_900017:triacetyl-beta-chitotriose'>PRD_900017</scene>, <scene name='pdbligand=TPQ:5-(2-CARBOXY-2-AMINOETHYL)-2-HYDROXY-1,4-BENZOQUINONE'>TPQ</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1tu5|1tu5]], [[1oac|1oac]], [[1ksi|1ksi]]</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=2pnc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2pnc OCA], [https://pdbe.org/2pnc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2pnc RCSB], [https://www.ebi.ac.uk/pdbsum/2pnc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2pnc ProSAT]</span></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Oxidoreductase Oxidoreductase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.4.3.21 and 1.4.3.22 1.4.3.21 and 1.4.3.22] </span></td></tr>
| + | |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2pnc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2pnc OCA], [http://pdbe.org/2pnc PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2pnc RCSB], [http://www.ebi.ac.uk/pdbsum/2pnc PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2pnc ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/AOCX_BOVIN AOCX_BOVIN] |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | ==See Also== | | ==See Also== |
| - | *[[Copper Amine Oxidase|Copper Amine Oxidase]] | + | *[[Copper amine oxidase 3D structures|Copper amine oxidase 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Bos taurus]] | | [[Category: Bos taurus]] |
| - | [[Category: Oxidoreductase]] | + | [[Category: Large Structures]] |
| - | [[Category: Cendron, L]] | + | [[Category: Cendron L]] |
| - | [[Category: Holt, A]] | + | [[Category: Di Paolo ML]] |
| - | [[Category: Paolo, M L.Di]] | + | [[Category: Holt A]] |
| - | [[Category: Rigo, A]] | + | [[Category: Rigo A]] |
| - | [[Category: Smith, D J]] | + | [[Category: Smith DJ]] |
| - | [[Category: Zanotti, G]] | + | [[Category: Zanotti G]] |
| - | [[Category: Amine oxidase]]
| + | |
| - | [[Category: Clonidine]]
| + | |
| - | [[Category: Quinoenzyme]]
| + | |
| - | [[Category: Tpq]]
| + | |
| Structural highlights
2pnc is a 2 chain structure with sequence from Bos taurus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Method: | X-ray diffraction, Resolution 2.4Å |
| Ligands: | , , , , , , |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
AOCX_BOVIN
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
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.
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[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Holt A, Smith DJ, Cendron L, Zanotti G, Rigo A, Di Paolo ML. Multiple binding sites for substrates and modulators of semicarbazide-sensitive amine oxidases: kinetic consequences. Mol Pharmacol. 2008 Feb;73(2):525-38. Epub 2007 Nov 7. PMID:17989349 doi:10.1124/mol.107.040964
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