6ocf: Difference between revisions
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<StructureSection load='6ocf' size='340' side='right'caption='[[6ocf]], [[Resolution|resolution]] 2.10Å' scene=''> | <StructureSection load='6ocf' size='340' side='right'caption='[[6ocf]], [[Resolution|resolution]] 2.10Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[6ocf]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6OCF OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6OCF FirstGlance]. <br> | <table><tr><td colspan='2'>[[6ocf]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6OCF OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6OCF FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr> | ||
<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene></td></tr> | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene></td></tr> | ||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">VASH1, KIAA1036, VASH ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), SVBP, CCDC23 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | |||
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Tubulinyl-Tyr_carboxypeptidase Tubulinyl-Tyr carboxypeptidase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.17.17 3.4.17.17] </span></td></tr> | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Tubulinyl-Tyr_carboxypeptidase Tubulinyl-Tyr carboxypeptidase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.17.17 3.4.17.17] </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=6ocf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ocf OCA], [http://pdbe.org/6ocf PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6ocf RCSB], [http://www.ebi.ac.uk/pdbsum/6ocf PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6ocf ProSAT]</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=6ocf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ocf OCA], [http://pdbe.org/6ocf PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6ocf RCSB], [http://www.ebi.ac.uk/pdbsum/6ocf PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6ocf ProSAT]</span></td></tr> | ||
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== Function == | == Function == | ||
[[http://www.uniprot.org/uniprot/VASH1_HUMAN VASH1_HUMAN]] Tyrosine carboxypeptidase that removes the C-terminal tyrosine residue of alpha-tubulin, thereby regulating microtubule dynamics and function (PubMed:29146869). Acts as an angiogenesis inhibitor: inhibits migration, proliferation and network formation by endothelial cells as well as angiogenesis (PubMed:15467828, PubMed:16488400, PubMed:16707096, PubMed:19204325). This inhibitory effect is selective to endothelial cells as it does not affect the migration of smooth muscle cells or fibroblasts (PubMed:15467828, PubMed:16488400, PubMed:16707096).<ref>PMID:15467828</ref> <ref>PMID:16488400</ref> <ref>PMID:16707096</ref> <ref>PMID:19204325</ref> <ref>PMID:29146869</ref> [[http://www.uniprot.org/uniprot/SVBP_HUMAN SVBP_HUMAN]] Enhances the tyrosine carboxypeptidase activity of VASH1 and VASH2, thereby promoting the removal of the C-terminal tyrosine residue of alpha-tubulin (PubMed:29146869). Also required to enhance the solubility and secretion of VASH1 and VASH2 (PubMed:20736312, PubMed:27879017).<ref>PMID:20736312</ref> <ref>PMID:27879017</ref> <ref>PMID:29146869</ref> | [[http://www.uniprot.org/uniprot/VASH1_HUMAN VASH1_HUMAN]] Tyrosine carboxypeptidase that removes the C-terminal tyrosine residue of alpha-tubulin, thereby regulating microtubule dynamics and function (PubMed:29146869). Acts as an angiogenesis inhibitor: inhibits migration, proliferation and network formation by endothelial cells as well as angiogenesis (PubMed:15467828, PubMed:16488400, PubMed:16707096, PubMed:19204325). This inhibitory effect is selective to endothelial cells as it does not affect the migration of smooth muscle cells or fibroblasts (PubMed:15467828, PubMed:16488400, PubMed:16707096).<ref>PMID:15467828</ref> <ref>PMID:16488400</ref> <ref>PMID:16707096</ref> <ref>PMID:19204325</ref> <ref>PMID:29146869</ref> [[http://www.uniprot.org/uniprot/SVBP_HUMAN SVBP_HUMAN]] Enhances the tyrosine carboxypeptidase activity of VASH1 and VASH2, thereby promoting the removal of the C-terminal tyrosine residue of alpha-tubulin (PubMed:29146869). Also required to enhance the solubility and secretion of VASH1 and VASH2 (PubMed:20736312, PubMed:27879017).<ref>PMID:20736312</ref> <ref>PMID:27879017</ref> <ref>PMID:29146869</ref> | ||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Microtubules are regulated by post-translational modifications of tubulin. The ligation and cleavage of the carboxy-terminal tyrosine of alpha-tubulin impact microtubule functions during mitosis, cardiomyocyte contraction and neuronal processes. Tubulin tyrosination and detyrosination are mediated by tubulin tyrosine ligase and the recently discovered tubulin detyrosinases, vasohibin 1 and 2 (VASH1 and VASH2) bound to the small vasohibin-binding protein (SVBP). Here, we report the crystal structures of human VASH1-SVBP alone, in complex with a tyrosine-derived covalent inhibitor and bound to the natural product parthenolide. The structures and subsequent mutagenesis analyses explain the requirement for SVBP during tubulin detyrosination, and reveal the basis for the recognition of the C-terminal tyrosine and the acidic alpha-tubulin tail by VASH1. The VASH1-SVBP-parthenolide structure provides a framework for designing more effective chemical inhibitors of vasohibins, which can be valuable for dissecting their biological functions and may have therapeutic potential. | |||
Structural basis of tubulin detyrosination by vasohibins.,Li F, Hu Y, Qi S, Luo X, Yu H Nat Struct Mol Biol. 2019 Jul;26(7):583-591. doi: 10.1038/s41594-019-0242-x. Epub, 2019 Jun 24. PMID:31235910<ref>PMID:31235910</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 6ocf" style="background-color:#fffaf0;"></div> | |||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Human]] | |||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Tubulinyl-Tyr carboxypeptidase]] | [[Category: Tubulinyl-Tyr carboxypeptidase]] | ||
Revision as of 09:32, 10 July 2019
The crystal structure of VASH1-SVBP complexThe crystal structure of VASH1-SVBP complex
Structural highlights
Function[VASH1_HUMAN] Tyrosine carboxypeptidase that removes the C-terminal tyrosine residue of alpha-tubulin, thereby regulating microtubule dynamics and function (PubMed:29146869). Acts as an angiogenesis inhibitor: inhibits migration, proliferation and network formation by endothelial cells as well as angiogenesis (PubMed:15467828, PubMed:16488400, PubMed:16707096, PubMed:19204325). This inhibitory effect is selective to endothelial cells as it does not affect the migration of smooth muscle cells or fibroblasts (PubMed:15467828, PubMed:16488400, PubMed:16707096).[1] [2] [3] [4] [5] [SVBP_HUMAN] Enhances the tyrosine carboxypeptidase activity of VASH1 and VASH2, thereby promoting the removal of the C-terminal tyrosine residue of alpha-tubulin (PubMed:29146869). Also required to enhance the solubility and secretion of VASH1 and VASH2 (PubMed:20736312, PubMed:27879017).[6] [7] [8] Publication Abstract from PubMedMicrotubules are regulated by post-translational modifications of tubulin. The ligation and cleavage of the carboxy-terminal tyrosine of alpha-tubulin impact microtubule functions during mitosis, cardiomyocyte contraction and neuronal processes. Tubulin tyrosination and detyrosination are mediated by tubulin tyrosine ligase and the recently discovered tubulin detyrosinases, vasohibin 1 and 2 (VASH1 and VASH2) bound to the small vasohibin-binding protein (SVBP). Here, we report the crystal structures of human VASH1-SVBP alone, in complex with a tyrosine-derived covalent inhibitor and bound to the natural product parthenolide. The structures and subsequent mutagenesis analyses explain the requirement for SVBP during tubulin detyrosination, and reveal the basis for the recognition of the C-terminal tyrosine and the acidic alpha-tubulin tail by VASH1. The VASH1-SVBP-parthenolide structure provides a framework for designing more effective chemical inhibitors of vasohibins, which can be valuable for dissecting their biological functions and may have therapeutic potential. Structural basis of tubulin detyrosination by vasohibins.,Li F, Hu Y, Qi S, Luo X, Yu H Nat Struct Mol Biol. 2019 Jul;26(7):583-591. doi: 10.1038/s41594-019-0242-x. Epub, 2019 Jun 24. PMID:31235910[9] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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