6j4q: Difference between revisions
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<StructureSection load='6j4q' size='340' side='right'caption='[[6j4q]], [[Resolution|resolution]] 2.70Å' scene=''> | <StructureSection load='6j4q' size='340' side='right'caption='[[6j4q]], [[Resolution|resolution]] 2.70Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[6j4q]] is a 8 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6J4Q OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6J4Q FirstGlance]. <br> | <table><tr><td colspan='2'>[[6j4q]] is a 8 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=6J4Q OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6J4Q FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=TQ8:N-[(2S)-4-CHLORO-3-OXO-1-PHENYL-BUTAN-2-YL]-4-METHYL-BENZENESULFONAMIDE'>TQ8</scene></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=TQ8:N-[(2S)-4-CHLORO-3-OXO-1-PHENYL-BUTAN-2-YL]-4-METHYL-BENZENESULFONAMIDE'>TQ8</scene></td></tr> | ||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">VASH2, VASHL ([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=6j4q FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6j4q OCA], [http://pdbe.org/6j4q PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6j4q RCSB], [http://www.ebi.ac.uk/pdbsum/6j4q PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6j4q 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=6j4q FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6j4q OCA], [http://pdbe.org/6j4q PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6j4q RCSB], [http://www.ebi.ac.uk/pdbsum/6j4q PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6j4q ProSAT]</span></td></tr> | ||
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== Function == | == Function == | ||
[[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/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 == | |||
Vasohibins are tubulin tyrosine carboxypeptidases that are important in neuron physiology. We examined the crystal structures of human vasohibin 1 and 2 in complex with small vasohibin-binding protein (SVBP) in the absence and presence of different inhibitors and a C-terminal alpha-tubulin peptide. In combination with functional data, we propose that SVBP acts as an activator of vasohibins. An extended groove and a distinctive surface residue patch of vasohibins define the specific determinants for recognizing and cleaving the C-terminal tyrosine of alpha-tubulin and for binding microtubules, respectively. The vasohibin-SVBP interaction and the ability of the enzyme complex to associate with microtubules regulate axon specification of neurons. Our results define the structural basis of tubulin detyrosination by vasohibins and show the relevance of this process for neuronal development. Our findings offer a unique platform for developing drugs against human conditions with abnormal tubulin tyrosination levels, such as cancer, heart defects and possibly brain disorders. | |||
Structural basis of tubulin detyrosination by the vasohibin-SVBP enzyme complex.,Wang N, Bosc C, Ryul Choi S, Boulan B, Peris L, Olieric N, Bao H, Krichen F, Chen L, Andrieux A, Olieric V, Moutin MJ, Steinmetz MO, Huang H Nat Struct Mol Biol. 2019 Jul;26(7):571-582. doi: 10.1038/s41594-019-0241-y. Epub, 2019 Jun 24. PMID:31235911<ref>PMID:31235911</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 6j4q" 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 14:33, 13 November 2019
Structural basis of tubulin detyrosination by vasohibins-SVBP enzyme complex and functional implicationsStructural basis of tubulin detyrosination by vasohibins-SVBP enzyme complex and functional implications
Structural highlights
Function[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).[1] [2] [3] Publication Abstract from PubMedVasohibins are tubulin tyrosine carboxypeptidases that are important in neuron physiology. We examined the crystal structures of human vasohibin 1 and 2 in complex with small vasohibin-binding protein (SVBP) in the absence and presence of different inhibitors and a C-terminal alpha-tubulin peptide. In combination with functional data, we propose that SVBP acts as an activator of vasohibins. An extended groove and a distinctive surface residue patch of vasohibins define the specific determinants for recognizing and cleaving the C-terminal tyrosine of alpha-tubulin and for binding microtubules, respectively. The vasohibin-SVBP interaction and the ability of the enzyme complex to associate with microtubules regulate axon specification of neurons. Our results define the structural basis of tubulin detyrosination by vasohibins and show the relevance of this process for neuronal development. Our findings offer a unique platform for developing drugs against human conditions with abnormal tubulin tyrosination levels, such as cancer, heart defects and possibly brain disorders. Structural basis of tubulin detyrosination by the vasohibin-SVBP enzyme complex.,Wang N, Bosc C, Ryul Choi S, Boulan B, Peris L, Olieric N, Bao H, Krichen F, Chen L, Andrieux A, Olieric V, Moutin MJ, Steinmetz MO, Huang H Nat Struct Mol Biol. 2019 Jul;26(7):571-582. doi: 10.1038/s41594-019-0241-y. Epub, 2019 Jun 24. PMID:31235911[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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