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4bty

From Proteopedia

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Current revision

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

Structural highlights

4bty is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 3.1Å
Ligands:	, , , , , ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

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.^[1] ^[2] ^[3]

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^[4]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Smith DJ, Salmi M, Bono P, Hellman J, Leu T, Jalkanen S. Cloning of vascular adhesion protein 1 reveals a novel multifunctional adhesion molecule. J Exp Med. 1998 Jul 6;188(1):17-27. PMID:9653080
↑ Bour S, Daviaud D, Gres S, Lefort C, Prevot D, Zorzano A, Wabitsch M, Saulnier-Blache JS, Valet P, Carpene C. Adipogenesis-related increase of semicarbazide-sensitive amine oxidase and monoamine oxidase in human adipocytes. Biochimie. 2007 Aug;89(8):916-25. Epub 2007 Feb 24. PMID:17400359 doi:http://dx.doi.org/10.1016/j.biochi.2007.02.013
↑ Kaitaniemi S, Elovaara H, Gron K, Kidron H, Liukkonen J, Salminen T, Salmi M, Jalkanen S, Elima K. The unique substrate specificity of human AOC2, a semicarbazide-sensitive amine oxidase. Cell Mol Life Sci. 2009 Aug;66(16):2743-57. doi: 10.1007/s00018-009-0076-5. Epub , 2009 Jul 9. PMID:19588076 doi:http://dx.doi.org/10.1007/s00018-009-0076-5
↑ Bligt-Linden E, Pihlavisto M, Szatmari I, Otwinowski Z, Smith DJ, Lazar L, Fulop F, Salminen TA. Novel Pyridazinone Inhibitors for Vascular Adhesion Protein-1 (VAP-1): Old Target-New Inhibition Mode. J Med Chem. 2013 Dec 13. PMID:24304424 doi:http://dx.doi.org/10.1021/jm401372d

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 See Also
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4bty"

@@ Line 3: / Line 3: @@
 <StructureSection load='4bty' size='340' side='right'caption='[[4bty]], [[Resolution|resolution]] 3.10&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[4bty]] 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=4BTY OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4BTY FirstGlance]. <br>
+<table><tr><td colspan='2'>[[4bty]] 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=4BTY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4BTY 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=JWF:5-[4-(4-METHYLPIPERAZIN-1-YL)PHENYLAMINO]-2-(4-CHLOROPHENYL)-6-(1H-1,2,4-TRIAZOL-5-YL)-3(2H)-PYRIDAZINONE'>JWF</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='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.1&#8491;</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=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=JWF:5-[4-(4-METHYLPIPERAZIN-1-YL)PHENYLAMINO]-2-(4-CHLOROPHENYL)-6-(1H-1,2,4-TRIAZOL-5-YL)-3(2H)-PYRIDAZINONE'>JWF</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='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4btw|4btw]], [[4btx|4btx]]</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=4bty FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4bty OCA], [https://pdbe.org/4bty PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4bty RCSB], [https://www.ebi.ac.uk/pdbsum/4bty PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4bty 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/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=4bty FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4bty OCA], [http://pdbe.org/4bty PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4bty RCSB], [http://www.ebi.ac.uk/pdbsum/4bty PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4bty ProSAT]</span></td></tr>
 </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>
+[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 ==
@@ Line 23: / Line 21: @@
 ==See Also==
-*[[Copper Amine Oxidase|Copper Amine Oxidase]]
+*[[Copper amine oxidase 3D structures|Copper amine oxidase 3D structures]]
 == References ==
 <references/>
@@ Line 30: / Line 28: @@
 [[Category: Homo sapiens]]
 [[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]]

4bty

From Proteopedia

Current revision

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

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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