|
|
| Line 3: |
Line 3: |
| | <StructureSection load='5lov' size='340' side='right'caption='[[5lov]], [[Resolution|resolution]] 2.40Å' scene=''> | | <StructureSection load='5lov' size='340' side='right'caption='[[5lov]], [[Resolution|resolution]] 2.40Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5lov]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/Bos_taurus Bos taurus], [http://en.wikipedia.org/wiki/Buffalo_rat Buffalo rat] and [http://en.wikipedia.org/wiki/Chick Chick]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5LOV OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5LOV FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5lov]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Bos_taurus Bos taurus], [https://en.wikipedia.org/wiki/Gallus_gallus Gallus gallus] and [https://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5LOV OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5LOV FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=71E:DZ+2384'>71E</scene>, <scene name='pdbligand=ACP:PHOSPHOMETHYLPHOSPHONIC+ACID+ADENYLATE+ESTER'>ACP</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=GDP:GUANOSINE-5-DIPHOSPHATE'>GDP</scene>, <scene name='pdbligand=GTP:GUANOSINE-5-TRIPHOSPHATE'>GTP</scene>, <scene name='pdbligand=MES:2-(N-MORPHOLINO)-ETHANESULFONIC+ACID'>MES</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</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]] 2.4Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5j2t|5j2t]], [[4i55|4i55]]</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=71E:DZ+2384'>71E</scene>, <scene name='pdbligand=ACP:PHOSPHOMETHYLPHOSPHONIC+ACID+ADENYLATE+ESTER'>ACP</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=GDP:GUANOSINE-5-DIPHOSPHATE'>GDP</scene>, <scene name='pdbligand=GTP:GUANOSINE-5-TRIPHOSPHATE'>GTP</scene>, <scene name='pdbligand=MES:2-(N-MORPHOLINO)-ETHANESULFONIC+ACID'>MES</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Stmn4 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10116 Buffalo rat]), TTL ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9031 CHICK])</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=5lov FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5lov OCA], [https://pdbe.org/5lov PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5lov RCSB], [https://www.ebi.ac.uk/pdbsum/5lov PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5lov ProSAT]</span></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=5lov FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5lov OCA], [http://pdbe.org/5lov PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5lov RCSB], [http://www.ebi.ac.uk/pdbsum/5lov PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5lov ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/TBA1B_BOVIN TBA1B_BOVIN]] Tubulin is the major constituent of microtubules. It binds two moles of GTP, one at an exchangeable site on the beta chain and one at a non-exchangeable site on the alpha chain. [[http://www.uniprot.org/uniprot/STMN4_RAT STMN4_RAT]] Exhibits microtubule-destabilizing activity.<ref>PMID:15039434</ref> <ref>PMID:12111843</ref> <ref>PMID:15014504</ref> [[http://www.uniprot.org/uniprot/TBB2B_BOVIN TBB2B_BOVIN]] Tubulin is the major constituent of microtubules. It binds two moles of GTP, one at an exchangeable site on the beta chain and one at a non-exchangeable site on the alpha chain (By similarity). | + | [https://www.uniprot.org/uniprot/TBA1B_BOVIN TBA1B_BOVIN] Tubulin is the major constituent of microtubules. It binds two moles of GTP, one at an exchangeable site on the beta chain and one at a non-exchangeable site on the alpha chain. |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
| Line 23: |
Line 22: |
| | ==See Also== | | ==See Also== |
| | *[[Stathmin-4 3D structures|Stathmin-4 3D structures]] | | *[[Stathmin-4 3D structures|Stathmin-4 3D structures]] |
| - | *[[Tubulin 3D Structures|Tubulin 3D Structures]] | |
| | *[[Tubulin tyrosine ligase|Tubulin tyrosine ligase]] | | *[[Tubulin tyrosine ligase|Tubulin tyrosine ligase]] |
| - | *[[User:Alisa Cario|User:Alisa Cario]] | |
| | == References == | | == References == |
| | <references/> | | <references/> |
| Line 31: |
Line 28: |
| | </StructureSection> | | </StructureSection> |
| | [[Category: Bos taurus]] | | [[Category: Bos taurus]] |
| - | [[Category: Buffalo rat]] | + | [[Category: Gallus gallus]] |
| - | [[Category: Chick]]
| + | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Brouhard, G]] | + | [[Category: Rattus norvegicus]] |
| - | [[Category: Prota, A E]] | + | [[Category: Brouhard G]] |
| - | [[Category: Roulston, A]]
| + | [[Category: Prota AE]] |
| - | [[Category: Shore, G C]]
| + | [[Category: Roulston A]] |
| - | [[Category: Steinmetz, M O]] | + | [[Category: Shore GC]] |
| - | [[Category: Cell cycle]] | + | [[Category: Steinmetz MO]] |
| - | [[Category: Cytoskeleton]] | + | |
| - | [[Category: Microtubule]] | + | |
| - | [[Category: Tubulin fold]]
| + | |
| Structural highlights
5lov is a 6 chain structure with sequence from Bos taurus, Gallus gallus and Rattus norvegicus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Method: | X-ray diffraction, Resolution 2.4Å |
| Ligands: | , , , , , , |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
TBA1B_BOVIN Tubulin is the major constituent of microtubules. It binds two moles of GTP, one at an exchangeable site on the beta chain and one at a non-exchangeable site on the alpha chain.
Publication Abstract from PubMed
Microtubule-targeting agents (MTAs) are widely used anticancer agents, but toxicities such as neuropathy limit their clinical use. MTAs bind to and alter the stability of microtubules, causing cell death in mitosis. We describe DZ-2384, a preclinical compound that exhibits potent antitumor activity in models of multiple cancer types. It has an unusually high safety margin and lacks neurotoxicity in rats at effective plasma concentrations. DZ-2384 binds the vinca domain of tubulin in a distinct way, imparting structurally and functionally different effects on microtubule dynamics compared to other vinca-binding compounds. X-ray crystallography and electron microscopy studies demonstrate that DZ-2384 causes straightening of curved protofilaments, an effect proposed to favor polymerization of tubulin. Both DZ-2384 and the vinca alkaloid vinorelbine inhibit microtubule growth rate; however, DZ-2384 increases the rescue frequency and preserves the microtubule network in nonmitotic cells and in primary neurons. This differential modulation of tubulin results in a potent MTA therapeutic with enhanced safety.
The synthetic diazonamide DZ-2384 has distinct effects on microtubule curvature and dynamics without neurotoxicity.,Wieczorek M, Tcherkezian J, Bernier C, Prota AE, Chaaban S, Rolland Y, Godbout C, Hancock MA, Arezzo JC, Ocal O, Rocha C, Olieric N, Hall A, Ding H, Bramoulle A, Annis MG, Zogopoulos G, Harran PG, Wilkie TM, Brekken RA, Siegel PM, Steinmetz MO, Shore GC, Brouhard GJ, Roulston A Sci Transl Med. 2016 Nov 16;8(365):365ra159. PMID:27856798[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Wieczorek M, Tcherkezian J, Bernier C, Prota AE, Chaaban S, Rolland Y, Godbout C, Hancock MA, Arezzo JC, Ocal O, Rocha C, Olieric N, Hall A, Ding H, Bramoulle A, Annis MG, Zogopoulos G, Harran PG, Wilkie TM, Brekken RA, Siegel PM, Steinmetz MO, Shore GC, Brouhard GJ, Roulston A. The synthetic diazonamide DZ-2384 has distinct effects on microtubule curvature and dynamics without neurotoxicity. Sci Transl Med. 2016 Nov 16;8(365):365ra159. PMID:27856798 doi:http://dx.doi.org/10.1126/scitranslmed.aag1093
|
