2pnc

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
(New page: 200px<br /><applet load="2pnc" size="350" color="white" frame="true" align="right" spinBox="true" caption="2pnc, resolution 2.40&Aring;" /> '''Crystal Structure of...)
Current revision (11:05, 30 August 2023) (edit) (undo)
 
(17 intermediate revisions not shown.)
Line 1: Line 1:
-
[[Image:2pnc.jpg|left|200px]]<br /><applet load="2pnc" size="350" color="white" frame="true" align="right" spinBox="true"
 
-
caption="2pnc, resolution 2.40&Aring;" />
 
-
'''Crystal Structure of Bovine Plasma Copper-Containing Amine Oxidase in Complex with Clonidine'''<br />
 
-
==Overview==
+
==Crystal Structure of Bovine Plasma Copper-Containing Amine Oxidase in Complex with Clonidine==
 +
<StructureSection load='2pnc' size='340' side='right'caption='[[2pnc]], [[Resolution|resolution]] 2.40&Aring;' scene=''>
 +
== Structural highlights ==
 +
<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='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.4&#8491;</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='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>
 +
</table>
 +
== Function ==
 +
[https://www.uniprot.org/uniprot/AOCX_BOVIN AOCX_BOVIN]
 +
== Evolutionary Conservation ==
 +
[[Image:Consurf_key_small.gif|200px|right]]
 +
Check<jmol>
 +
<jmolCheckbox>
 +
<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/pn/2pnc_consurf.spt"</scriptWhenChecked>
 +
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
 +
<text>to colour the structure by Evolutionary Conservation</text>
 +
</jmolCheckbox>
 +
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2pnc ConSurf].
 +
<div style="clear:both"></div>
 +
<div style="background-color:#fffaf0;">
 +
== 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.
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==
+
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<ref>PMID:17989349</ref>
-
2PNC is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Bos_taurus Bos taurus] with <scene name='pdbligand=CU:'>CU</scene>, <scene name='pdbligand=CA:'>CA</scene>, <scene name='pdbligand=CL:'>CL</scene> and <scene name='pdbligand=CLU:'>CLU</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [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] Known structural/functional Sites: <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>. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2PNC OCA].
+
-
==Reference==
+
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-
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://ispc.weizmann.ac.il//pmbin/getpm?pmid=17989349 17989349]
+
</div>
-
[[Category: Amine oxidase (copper-containing)]]
+
<div class="pdbe-citations 2pnc" style="background-color:#fffaf0;"></div>
-
[[Category: Bos taurus]]
+
-
[[Category: Single protein]]
+
-
[[Category: Cendron, L.]]
+
-
[[Category: Holt, A.]]
+
-
[[Category: Paolo, M L.Di.]]
+
-
[[Category: Rigo, A.]]
+
-
[[Category: Smith, D J.]]
+
-
[[Category: Zanotti, G.]]
+
-
[[Category: CA]]
+
-
[[Category: CL]]
+
-
[[Category: CLU]]
+
-
[[Category: CU]]
+
-
[[Category: amine oxidase]]
+
-
[[Category: clonidine]]
+
-
[[Category: copper]]
+
-
[[Category: oxidoreductase]]
+
-
[[Category: quinoenzyme]]
+
-
[[Category: tpq]]
+
-
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Feb 27 07:58:40 2008''
+
==See Also==
 +
*[[Copper amine oxidase 3D structures|Copper amine oxidase 3D structures]]
 +
== References ==
 +
<references/>
 +
__TOC__
 +
</StructureSection>
 +
[[Category: Bos taurus]]
 +
[[Category: Large Structures]]
 +
[[Category: Cendron L]]
 +
[[Category: Di Paolo ML]]
 +
[[Category: Holt A]]
 +
[[Category: Rigo A]]
 +
[[Category: Smith DJ]]
 +
[[Category: Zanotti G]]

Current revision

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

PDB ID 2pnc

Drag the structure with the mouse to rotate

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2pnc"
Personal tools