4btw - Revision history

OCA at 11:57, 20 December 2023

2023-12-20T11:57:58Z

←Older revision		Revision as of 11:57, 20 December 2023
Line 4:		Line 4:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4btw]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4BTW OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4BTW FirstGlance]. <br>		<table><tr><td colspan='2'>[[4btw]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4BTW OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4BTW FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=CU:COPPER+(II)+ION'>CU</scene>, <scene name='pdbligand=JW7:5-(CYCLOHEXYLAMINO)-2-PHENYL-6-(1H-1,2,4-TRIAZOL-5-YL)-3(2H)-PYRIDAZINONE'>JW7</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=TPQ:5-(2-CARBOXY-2-AMINOETHYL)-2-HYDROXY-1,4-BENZOQUINONE'>TPQ</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]] 2.8Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=CU:COPPER+(II)+ION'>CU</scene>, <scene name='pdbligand=JW7:5-(CYCLOHEXYLAMINO)-2-PHENYL-6-(1H-1,2,4-TRIAZOL-5-YL)-3(2H)-PYRIDAZINONE'>JW7</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</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=4btw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4btw OCA], [https://pdbe.org/4btw PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4btw RCSB], [https://www.ebi.ac.uk/pdbsum/4btw PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4btw ProSAT]</span></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=4btw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4btw OCA], [https://pdbe.org/4btw PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4btw RCSB], [https://www.ebi.ac.uk/pdbsum/4btw PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4btw ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
-	[[https://www.uniprot.org/uniprot/AOC3_HUMAN AOC3_HUMAN]] Cell adhesion protein that participates in lymphocyte recirculation by mediating the binding of lymphocytes to peripheral lymph node vascular endothelial cells in an L-selectin-independent fashion. Has a monoamine oxidase activity. May play a role in adipogenesis.<ref>PMID:9653080</ref> <ref>PMID:17400359</ref> <ref>PMID:19588076</ref>	+	[https://www.uniprot.org/uniprot/AOC3_HUMAN AOC3_HUMAN] Cell adhesion protein that participates in lymphocyte recirculation by mediating the binding of lymphocytes to peripheral lymph node vascular endothelial cells in an L-selectin-independent fashion. Has a monoamine oxidase activity. May play a role in adipogenesis.<ref>PMID:9653080</ref> <ref>PMID:17400359</ref> <ref>PMID:19588076</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Vascular adhesion protein-1 (VAP-1) is a primary amine oxidase and a drug target for inflammatory and vascular diseases. Despite extensive attempts to develop potent, specific, and reversible inhibitors of its enzyme activity, the task has proven challenging. Here we report the synthesis, inhibitory activity, and molecular binding mode of novel pyridazinone inhibitors, which show specificity for VAP-1 over monoamine and diamine oxidases. The crystal structures of three inhibitor-VAP-1 complexes show that these compounds bind reversibly into a unique binding site in the active site channel. Although they are good inhibitors of human VAP-1, they do not inhibit rodent VAP-1 well. To investigate this further, we used homology modeling and structural comparison to identify amino acid differences, which explain the species-specific binding properties. Our results prove the potency and specificity of these new inhibitors, and the detailed characterization of their binding mode is of importance for further development of VAP-1 inhibitors.
		+
		+	Novel Pyridazinone Inhibitors for Vascular Adhesion Protein-1 (VAP-1): Old Target-New Inhibition Mode.,Bligt-Linden E, Pihlavisto M, Szatmari I, Otwinowski Z, Smith DJ, Lazar L, Fulop F, Salminen TA J Med Chem. 2013 Dec 13. PMID:24304424<ref>PMID:24304424</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 4btw" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==

OCA at 17:07, 7 September 2022

2022-09-07T17:07:56Z

←Older revision		Revision as of 17:07, 7 September 2022
Line 3:		Line 3:
	<StructureSection load='4btw' size='340' side='right'caption='[[4btw]], [[Resolution\|resolution]] 2.80Å' scene=''>		<StructureSection load='4btw' size='340' side='right'caption='[[4btw]], [[Resolution\|resolution]] 2.80Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4btw]] is a 2 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4BTW OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=4BTW FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4btw]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4BTW OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4BTW FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=CU:COPPER+(II)+ION'>CU</scene>, <scene name='pdbligand=JW7:5-(CYCLOHEXYLAMINO)-2-PHENYL-6-(1H-1,2,4-TRIAZOL-5-YL)-3(2H)-PYRIDAZINONE'>JW7</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>~~</td></tr>~~	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=CU:COPPER+(II)+ION'>CU</scene>, <scene name='pdbligand=JW7:5-(CYCLOHEXYLAMINO)-2-PHENYL-6-(1H-1,2,4-TRIAZOL-5-YL)-3(2H)-PYRIDAZINONE'>JW7</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=TPQ:5-(2-CARBOXY-2-AMINOETHYL)-2-HYDROXY-1,4-BENZOQUINONE'>TPQ</scene></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='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4btw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4btw OCA], [https://pdbe.org/4btw PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4btw RCSB], [https://www.ebi.ac.uk/pdbsum/4btw PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4btw ProSAT]</span></td></tr>
-	~~<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4btx\|4btx]], [[4bty\|4bty]]</td></tr>~~	+
-	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Primary-amine_oxidase Primary-amine oxidase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.4.3.21 1.4.3.21] </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=4btw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4btw OCA], [~~http~~://pdbe.org/4btw PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=4btw RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/4btw PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=4btw ProSAT]</span></td></tr>	+
	</table>		</table>
	== Function ==		== Function ==
-	[[~~http~~://www.uniprot.org/uniprot/AOC3_HUMAN AOC3_HUMAN]] Cell adhesion protein that participates in lymphocyte recirculation by mediating the binding of lymphocytes to peripheral lymph node vascular endothelial cells in an L-selectin-independent fashion. Has a monoamine oxidase activity. May play a role in adipogenesis.<ref>PMID:9653080</ref> <ref>PMID:17400359</ref> <ref>PMID:19588076</ref>	+	[[https://www.uniprot.org/uniprot/AOC3_HUMAN AOC3_HUMAN]] Cell adhesion protein that participates in lymphocyte recirculation by mediating the binding of lymphocytes to peripheral lymph node vascular endothelial cells in an L-selectin-independent fashion. Has a monoamine oxidase activity. May play a role in adipogenesis.<ref>PMID:9653080</ref> <ref>PMID:17400359</ref> <ref>PMID:19588076</ref>
-	~~<div style="background-color:#fffaf0;">~~	+
-	~~== Publication Abstract from PubMed ==~~	+
-	Vascular adhesion protein-1 (VAP-1) is a primary amine oxidase and a drug target for inflammatory and vascular diseases. Despite extensive attempts to develop potent, specific, and reversible inhibitors of its enzyme activity, the task has proven challenging. Here we report the synthesis, inhibitory activity, and molecular binding mode of novel pyridazinone inhibitors, which show specificity for VAP-1 over monoamine and diamine oxidases. The crystal structures of three inhibitor-VAP-1 complexes show that these compounds bind reversibly into a unique binding site in the active site channel. Although they are good inhibitors of human VAP-1, they do not inhibit rodent VAP-1 well. To investigate this further, we used homology modeling and structural comparison to identify amino acid differences, which explain the species-specific binding properties. Our results prove the potency and specificity of these new inhibitors, and the detailed characterization of their binding mode is of importance for further development of VAP-1 inhibitors.	+
-		+
-	Novel Pyridazinone Inhibitors for Vascular Adhesion Protein-1 (VAP-1): Old Target-New Inhibition Mode.,Bligt-Linden E, Pihlavisto M, Szatmari I, Otwinowski Z, Smith DJ, Lazar L, Fulop F, Salminen TA J Med Chem. 2013 Dec 13. PMID:24304424<ref>PMID:24304424</ref>	+
-		+
-	~~From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>~~	+
-	~~</div>~~	+
-	~~<div class="pdbe-citations 4btw" style="background-color:#fffaf0;"></div~~>	+

	==See Also==		==See Also==
-	*[[Copper ~~Amine Oxidase~~\|Copper ~~Amine Oxidase~~]]	+	*[[Copper amine oxidase 3D structures\|Copper amine oxidase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
Line 30:		Line 18:
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	~~[[Category: Primary-amine oxidase]]~~	+	[[Category: Bligt-Linden E]]
-	[[Category: Bligt-Linden, E]]	+	[[Category: Fulop F]]
-	[[Category: Fulop, F]]	+	[[Category: Lazar L]]
-	[[Category: Lazar, L]]	+	[[Category: Otwinowski Z]]
-	[[Category: Otwinowski, Z]]	+	[[Category: Pihlavisto M]]
-	[[Category: Pihlavisto, M]]	+	[[Category: Salminen TA]]
-	[[Category: Salminen~~, T A~~]]	+	[[Category: Smith DJ]]
-	[[Category: Smith~~, D J~~]]	+	[[Category: Szatmari I]]
-	[[Category: Szatmari, I]]	+
-	~~[[Category: Oxidoreductase~~]]	+

OCA at 13:36, 13 March 2019

2019-03-13T13:36:28Z

←Older revision		Revision as of 13:36, 13 March 2019
Line 1:		Line 1:

	==Crystal structure of human vascular adhesion protein-1 in complex with pyridazinone inhibitors==		==Crystal structure of human vascular adhesion protein-1 in complex with pyridazinone inhibitors==
-	<StructureSection load='4btw' size='340' side='right' caption='[[4btw]], [[Resolution\|resolution]] 2.80Å' scene=''>	+	<StructureSection load='4btw' size='340' side='right'caption='[[4btw]], [[Resolution\|resolution]] 2.80Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4btw]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4BTW OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4BTW FirstGlance]. <br>		<table><tr><td colspan='2'>[[4btw]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4BTW OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4BTW FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=CU:COPPER+(II)+ION'>CU</scene>, <scene name='pdbligand=JW7:5-(CYCLOHEXYLAMINO)-2-PHENYL-6-(1H-1,2,4-TRIAZOL-5-YL)-3(2H)-PYRIDAZINONE'>JW7</scene>, <scene name='pdbligand=~~NAG~~:~~N-ACETYL~~-D-~~GLUCOSAMINE~~'>~~NAG~~</scene>, <scene name='pdbligand=~~MAN~~:~~ALPHA~~-D-~~MANNOSE~~'>~~MAN~~</scene></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=CU:COPPER+(II)+ION'>CU</scene>, <scene name='pdbligand=JW7:5-(CYCLOHEXYLAMINO)-2-PHENYL-6-(1H-1,2,4-TRIAZOL-5-YL)-3(2H)-PYRIDAZINONE'>JW7</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></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='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='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4btx\|4btx]], [[4bty\|4bty]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4btx\|4btx]], [[4bty\|4bty]]</td></tr>
Line 29:		Line 29:
	</StructureSection>		</StructureSection>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
		+	[[Category: Large Structures]]
	[[Category: Primary-amine oxidase]]		[[Category: Primary-amine oxidase]]
	[[Category: Bligt-Linden, E]]		[[Category: Bligt-Linden, E]]

OCA at 19:02, 5 August 2016

2016-08-05T19:02:55Z

←Older revision		Revision as of 19:02, 5 August 2016
Line 1:		Line 1:
		+
	==Crystal structure of human vascular adhesion protein-1 in complex with pyridazinone inhibitors==		==Crystal structure of human vascular adhesion protein-1 in complex with pyridazinone inhibitors==
	<StructureSection load='4btw' size='340' side='right' caption='[[4btw]], [[Resolution\|resolution]] 2.80Å' scene=''>		<StructureSection load='4btw' size='340' side='right' caption='[[4btw]], [[Resolution\|resolution]] 2.80Å' scene=''>
Line 7:		Line 8:
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4btx\|4btx]], [[4bty\|4bty]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4btx\|4btx]], [[4bty\|4bty]]</td></tr>
	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Primary-amine_oxidase Primary-amine oxidase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.4.3.21 1.4.3.21] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Primary-amine_oxidase Primary-amine oxidase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.4.3.21 1.4.3.21] </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=4btw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4btw OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4btw RCSB], [http://www.ebi.ac.uk/pdbsum/4btw PDBsum]</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=4btw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4btw OCA], [http://pdbe.org/4btw PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4btw RCSB], [http://www.ebi.ac.uk/pdbsum/4btw PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4btw ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 19:		Line 20:
	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>		From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
	</div>		</div>
		+	<div class="pdbe-citations 4btw" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==

OCA at 05:02, 25 December 2014

2014-12-25T05:02:42Z

←Older revision		Revision as of 05:02, 25 December 2014
Line 9:		Line 9:
	<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=4btw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4btw OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4btw RCSB], [http://www.ebi.ac.uk/pdbsum/4btw PDBsum]</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=4btw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4btw OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4btw RCSB], [http://www.ebi.ac.uk/pdbsum/4btw PDBsum]</span></td></tr>
	</table>		</table>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/AOC3_HUMAN AOC3_HUMAN]] Cell adhesion protein that participates in lymphocyte recirculation by mediating the binding of lymphocytes to peripheral lymph node vascular endothelial cells in an L-selectin-independent fashion. Has a monoamine oxidase activity. May play a role in adipogenesis.<ref>PMID:9653080</ref> <ref>PMID:17400359</ref> <ref>PMID:19588076</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==

OCA at 17:11, 21 December 2014

2014-12-21T17:11:25Z

←Older revision		Revision as of 17:11, 21 December 2014
Line 1:		Line 1:
-	~~{{STRUCTURE_4btw\| PDB=4btw \| SCENE= }}~~	+	==Crystal structure of human vascular adhesion protein-1 in complex with pyridazinone inhibitors==
-	===Crystal structure of human vascular adhesion protein-1 in complex with pyridazinone inhibitors===	+	<StructureSection load='4btw' size='340' side='right' caption='[[4btw]], [[Resolution\|resolution]] 2.80Å' scene=''>
-	~~{{ABSTRACT_PUBMED_24304424}}~~	+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[4btw]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4BTW OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4BTW FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=CU:COPPER+(II)+ION'>CU</scene>, <scene name='pdbligand=JW7:5-(CYCLOHEXYLAMINO)-2-PHENYL-6-(1H-1,2,4-TRIAZOL-5-YL)-3(2H)-PYRIDAZINONE'>JW7</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene></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='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4btx\|4btx]], [[4bty\|4bty]]</td></tr>
		+	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Primary-amine_oxidase Primary-amine oxidase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.4.3.21 1.4.3.21] </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=4btw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4btw OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4btw RCSB], [http://www.ebi.ac.uk/pdbsum/4btw PDBsum]</span></td></tr>
		+	</table>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Vascular adhesion protein-1 (VAP-1) is a primary amine oxidase and a drug target for inflammatory and vascular diseases. Despite extensive attempts to develop potent, specific, and reversible inhibitors of its enzyme activity, the task has proven challenging. Here we report the synthesis, inhibitory activity, and molecular binding mode of novel pyridazinone inhibitors, which show specificity for VAP-1 over monoamine and diamine oxidases. The crystal structures of three inhibitor-VAP-1 complexes show that these compounds bind reversibly into a unique binding site in the active site channel. Although they are good inhibitors of human VAP-1, they do not inhibit rodent VAP-1 well. To investigate this further, we used homology modeling and structural comparison to identify amino acid differences, which explain the species-specific binding properties. Our results prove the potency and specificity of these new inhibitors, and the detailed characterization of their binding mode is of importance for further development of VAP-1 inhibitors.

-	~~==Function==~~	+	Novel Pyridazinone Inhibitors for Vascular Adhesion Protein-1 (VAP-1): Old Target-New Inhibition Mode.,Bligt-Linden E, Pihlavisto M, Szatmari I, Otwinowski Z, Smith DJ, Lazar L, Fulop F, Salminen TA J Med Chem. 2013 Dec 13. PMID:24304424<ref>PMID:24304424</ref>
-	~~[[http~~:~~//www~~.uniprot.org/uniprot/AOC3_HUMAN AOC3_HUMAN]] Cell adhesion protein that participates in lymphocyte recirculation by mediating the binding of lymphocytes to peripheral lymph node vascular endothelial cells in an L~~-selectin-independent fashion~~. ~~Has a monoamine oxidase activity~~. ~~May play a role in adipogenesis.<ref>~~PMID:~~9653080</ref> <ref>PMID:17400359</ref>~~ <ref>PMID:~~19588076~~</ref>	+

-	~~==About this Structure==~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	~~[[4btw]] is~~ a ~~2 chain structure with sequence from [http://en~~.~~wikipedia~~.~~org/wiki/Homo_sapiens Homo sapiens]~~. ~~Full crystallographic information is available from [http:~~/~~/oca.weizmann.ac.il/oca-bin/ocashort?id=4BTW OCA].~~	+	</div>

-	==~~Reference~~==	+	==See Also==
-	~~<ref group~~=~~"xtra">PMID:024304424</ref>~~<references ~~group="xtra"~~/><~~references~~/>	+	*[[Copper Amine Oxidase\|Copper Amine Oxidase]]
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Primary-amine oxidase]]		[[Category: Primary-amine oxidase]]
-	[[Category: Bligt-Linden, E.]]	+	[[Category: Bligt-Linden, E]]
-	[[Category: Fulop, F.]]	+	[[Category: Fulop, F]]
-	[[Category: Lazar, L.]]	+	[[Category: Lazar, L]]
-	[[Category: Otwinowski, Z.]]	+	[[Category: Otwinowski, Z]]
-	[[Category: Pihlavisto, M.]]	+	[[Category: Pihlavisto, M]]
-	[[Category: Salminen, T A.]]	+	[[Category: Salminen, T A]]
-	[[Category: Smith, D J.]]	+	[[Category: Smith, D J]]
-	[[Category: Szatmari, I.]]	+	[[Category: Szatmari, I]]
	[[Category: Oxidoreductase]]		[[Category: Oxidoreductase]]

OCA at 10:24, 18 December 2013

2013-12-18T10:24:29Z

←Older revision		Revision as of 10:24, 18 December 2013
Line 1:		Line 1:
-	~~'''Unreleased~~ structure~~'''~~	+	{{STRUCTURE_4btw\| PDB=4btw \| SCENE= }}
		+	===Crystal structure of human vascular adhesion protein-1 in complex with pyridazinone inhibitors===
		+	{{ABSTRACT_PUBMED_24304424}}

-	~~The entry 4btw is ON HOLD~~ ~~until Paper Publication~~	+	==Function==
		+	[[http://www.uniprot.org/uniprot/AOC3_HUMAN AOC3_HUMAN]] Cell adhesion protein that participates in lymphocyte recirculation by mediating the binding of lymphocytes to peripheral lymph node vascular endothelial cells in an L-selectin-independent fashion. Has a monoamine oxidase activity. May play a role in adipogenesis.<ref>PMID:9653080</ref> <ref>PMID:17400359</ref> <ref>PMID:19588076</ref>

-	~~Authors~~: ~~Bligt-Linden, E~~.~~, Pihlavisto, M~~.~~, Szatmari, I~~.~~, Otwinowski, Z~~.~~, Smith, D~~.J.~~, Lazar, L., Fulop, F., Salminen, T.A~~.	+	==About this Structure==
		+	[[4btw]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4BTW OCA].

-	~~Description~~: ~~Crystal structure of human vascular adhesion protein~~-~~1 in complex with pyridazinone inhibitors~~	+	==Reference==
		+	<ref group="xtra">PMID:024304424</ref><references group="xtra"/><references/>
		+	[[Category: Homo sapiens]]
		+	[[Category: Primary-amine oxidase]]
		+	[[Category: Bligt-Linden, E.]]
		+	[[Category: Fulop, F.]]
		+	[[Category: Lazar, L.]]
		+	[[Category: Otwinowski, Z.]]
		+	[[Category: Pihlavisto, M.]]
		+	[[Category: Salminen, T A.]]
		+	[[Category: Smith, D J.]]
		+	[[Category: Szatmari, I.]]
		+	[[Category: Oxidoreductase]]

OCA at 06:20, 28 August 2013

2013-08-28T06:20:40Z

←Older revision		Revision as of 06:20, 28 August 2013
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 4btw is ON HOLD	+	The entry 4btw is ON HOLD until Paper Publication

	Authors: Bligt-Linden, E., Pihlavisto, M., Szatmari, I., Otwinowski, Z., Smith, D.J., Lazar, L., Fulop, F., Salminen, T.A.		Authors: Bligt-Linden, E., Pihlavisto, M., Szatmari, I., Otwinowski, Z., Smith, D.J., Lazar, L., Fulop, F., Salminen, T.A.

	Description: Crystal structure of human vascular adhesion protein-1 in complex with pyridazinone inhibitors		Description: Crystal structure of human vascular adhesion protein-1 in complex with pyridazinone inhibitors

OCA at 06:58, 14 August 2013

2013-08-14T06:58:45Z

←Older revision		Revision as of 06:58, 14 August 2013
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 4btw is ON HOLD ~~until sometime in the future~~	+	The entry 4btw is ON HOLD

	Authors: Bligt-Linden, E., Pihlavisto, M., Szatmari, I., Otwinowski, Z., Smith, D.J., Lazar, L., Fulop, F., Salminen, T.A.		Authors: Bligt-Linden, E., Pihlavisto, M., Szatmari, I., Otwinowski, Z., Smith, D.J., Lazar, L., Fulop, F., Salminen, T.A.

	Description: Crystal structure of human vascular adhesion protein-1 in complex with pyridazinone inhibitors		Description: Crystal structure of human vascular adhesion protein-1 in complex with pyridazinone inhibitors

OCA at 12:01, 24 July 2013

2013-07-24T12:01:45Z

←Older revision		Revision as of 12:01, 24 July 2013
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 4btw is ON HOLD	+	The entry 4btw is ON HOLD until sometime in the future

	Authors: Bligt-Linden, E., Pihlavisto, M., Szatmari, I., Otwinowski, Z., Smith, D.J., Lazar, L., Fulop, F., Salminen, T.A.		Authors: Bligt-Linden, E., Pihlavisto, M., Szatmari, I., Otwinowski, Z., Smith, D.J., Lazar, L., Fulop, F., Salminen, T.A.

	Description: Crystal structure of human vascular adhesion protein-1 in complex with pyridazinone inhibitors		Description: Crystal structure of human vascular adhesion protein-1 in complex with pyridazinone inhibitors