5ezy: Difference between revisions

Latest revision as of 04:03, 21 November 2024

Crystal structure of T2R-TTL-taccalonolide AJ complex

Structural highlights

5ezy is a 6 chain structure with sequence from Bos taurus, Gallus gallus, Rattus norvegicus and Sus scrofa. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.05Å
Ligands:	ACP, CA, GDP, GTP, MES, MG
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

TBA1B_PIG 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

As a major component of the cytoskeleton, microtubules consist of alphabeta-tubulin heterodimers and have been recognized as attractive targets for cancer chemotherapy. Microtubule-stabilizing agents (MSAs) promote polymerization of tubulin and stabilize the polymer, preventing depolymerization. The molecular mechanisms by which MSAs stabilize microtubules remain elusive. Here we report a 2.05 A crystal structure of tubulin complexed with taccalonolide AJ, a newly identified taxane-site MSA. Taccalonolide AJ covalently binds to beta-tubulin D226. On AJ binding, the M-loop undergoes a conformational shift to facilitate tubulin polymerization. In this tubulin-AJ complex, the E-site of tubulin is occupied by GTP rather than GDP. Biochemical analyses confirm that AJ inhibits the hydrolysis of the E-site GTP. Thus, we propose that the beta-tubulin E-site is locked into a GTP-preferred status by AJ binding. Our results provide experimental evidence for the connection between MSA binding and tubulin nucleotide state, and will help design new MSAs to overcome taxane resistance.

Mechanism of microtubule stabilization by taccalonolide AJ.,Wang Y, Yu Y, Li GB, Li SA, Wu C, Gigant B, Qin W, Chen H, Wu Y, Chen Q, Yang J Nat Commun. 2017 Jun 6;8:15787. doi: 10.1038/ncomms15787. PMID:28585532^[1]

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

References

↑ Wang Y, Yu Y, Li GB, Li SA, Wu C, Gigant B, Qin W, Chen H, Wu Y, Chen Q, Yang J. Mechanism of microtubule stabilization by taccalonolide AJ. Nat Commun. 2017 Jun 6;8:15787. doi: 10.1038/ncomms15787. PMID:28585532 doi:https://dx.doi.org/10.1038/ncomms15787

Proteopedia Page Contributors and Editors (what is this?)

OCA

[1] Wang Y, Yu Y, Li GB, Li SA, Wu C, Gigant B, Qin W, Chen H, Wu Y, Chen Q, Yang J. Mechanism of microtubule stabilization by taccalonolide AJ. Nat Commun. 2017 Jun 6;8:15787. doi: 10.1038/ncomms15787. PMID:28585532 doi:https://dx.doi.org/10.1038/ncomms15787

[1]

@@ Line 3: / Line 3: @@
 <StructureSection load='5ezy' size='340' side='right'caption='[[5ezy]], [[Resolution|resolution]] 2.05&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5ezy]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/ ], [http://en.wikipedia.org/wiki/Bos_taurus Bos taurus] and [http://en.wikipedia.org/wiki/Sus_scrofa Sus scrofa]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5EZY OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5EZY FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5ezy]] 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], [https://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus] and [https://en.wikipedia.org/wiki/Sus_scrofa Sus scrofa]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5EZY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5EZY FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><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>, <scene name='pdbligand=TAJ:TACCALONOLIDE+AJ'>TAJ</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]] 2.05&#8491;</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=5ezy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ezy OCA], [http://pdbe.org/5ezy PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5ezy RCSB], [http://www.ebi.ac.uk/pdbsum/5ezy PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5ezy ProSAT]</span></td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><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='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=5ezy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ezy OCA], [https://pdbe.org/5ezy PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5ezy RCSB], [https://www.ebi.ac.uk/pdbsum/5ezy PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5ezy ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[http://www.uniprot.org/uniprot/TBA1B_PIG TBA1B_PIG]] 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_PIG TBA1B_PIG] 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;">
 == Publication Abstract from PubMed ==
@@ Line 27: / Line 28: @@
 </StructureSection>
 [[Category: Bos taurus]]
+[[Category: Gallus gallus]]
 [[Category: Large Structures]]
+[[Category: Rattus norvegicus]]
 [[Category: Sus scrofa]]
-[[Category: Chen, Q]]
+[[Category: Chen Q]]
-[[Category: Wang, Y]]
+[[Category: Wang Y]]
-[[Category: Yang, J]]
+[[Category: Yang J]]
-[[Category: Yu, Y]]
+[[Category: Yu Y]]
-[[Category: Complex]]
-[[Category: Inhibitor]]
-[[Category: Structural protein]]
-[[Category: Tubulin]]

5ezy: Difference between revisions

Latest revision as of 04:03, 21 November 2024

Crystal structure of T2R-TTL-taccalonolide AJ complex

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

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