6fjf: Difference between revisions

Latest revision as of 05:37, 23 April 2025

Tubulin-FcMaytansine complex

Structural highlights

6fjf 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 2.402Å
Ligands:	ACP, CA, DMS, GDP, GTP, MES, MG, PEG
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) like taxol and vinblastine are among the most successful chemotherapeutic drugs against cancer. Here, we describe a fluorescence anisotropy-based assay that specifically probes for ligands targeting the recently discovered maytansine site of tubulin. Using this assay, we have determined the dissociation constants of known maytansine site ligands, including the pharmacologically active degradation product of the clinical antibody-drug conjugate trastuzumab emtansine. In addition, we discovered that the two natural products spongistatin-1 and disorazole Z with established cellular potency bind to the maytansine site on beta-tubulin. The high-resolution crystal structures of spongistatin-1 and disorazole Z in complex with tubulin allowed the definition of an additional sub-site adjacent to the pocket shared by all maytansine-site ligands, which could be exploitable as a distinct, separate target site for small molecules. Our study provides a basis for the discovery and development of next-generation MTAs for the treatment of cancer.

A fluorescence anisotropy assay to discover and characterize ligands targeting the maytansine site of tubulin.,Menchon G, Prota AE, Lucena-Agell D, Bucher P, Jansen R, Irschik H, Muller R, Paterson I, Diaz JF, Altmann KH, Steinmetz MO Nat Commun. 2018 May 29;9(1):2106. doi: 10.1038/s41467-018-04535-8. PMID:29844393^[1]

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

References

↑ Menchon G, Prota AE, Lucena-Agell D, Bucher P, Jansen R, Irschik H, Muller R, Paterson I, Diaz JF, Altmann KH, Steinmetz MO. A fluorescence anisotropy assay to discover and characterize ligands targeting the maytansine site of tubulin. Nat Commun. 2018 May 29;9(1):2106. doi: 10.1038/s41467-018-04535-8. PMID:29844393 doi:https://dx.doi.org/10.1038/s41467-018-04535-8

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OCA

[1] Menchon G, Prota AE, Lucena-Agell D, Bucher P, Jansen R, Irschik H, Muller R, Paterson I, Diaz JF, Altmann KH, Steinmetz MO. A fluorescence anisotropy assay to discover and characterize ligands targeting the maytansine site of tubulin. Nat Commun. 2018 May 29;9(1):2106. doi: 10.1038/s41467-018-04535-8. PMID:29844393 doi:https://dx.doi.org/10.1038/s41467-018-04535-8

[1]

@@ Line 1: / Line 1: @@
 ==Tubulin-FcMaytansine complex==
-<StructureSection load='6fjf' size='340' side='right' caption='[[6fjf]], [[Resolution|resolution]] 2.40&Aring;' scene=''>
+<StructureSection load='6fjf' size='340' side='right'caption='[[6fjf]], [[Resolution|resolution]] 2.40&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[6fjf]] 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=6FJF OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6FJF FirstGlance]. <br>
+<table><tr><td colspan='2'>[[6fjf]] 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=6FJF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6FJF FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACP:PHOSPHOMETHYLPHOSPHONIC+ACID+ADENYLATE+ESTER'>ACP</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=DKE:FcMaytansine'>DKE</scene>, <scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</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=PEG:DI(HYDROXYETHYL)ETHER'>PEG</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]] 2.402&#8491;</td></tr>
-<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[6fii|6fii]]</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=DMS:DIMETHYL+SULFOXIDE'>DMS</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=PEG:DI(HYDROXYETHYL)ETHER'>PEG</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=6fjf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6fjf OCA], [https://pdbe.org/6fjf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6fjf RCSB], [https://www.ebi.ac.uk/pdbsum/6fjf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6fjf 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=6fjf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6fjf OCA], [http://pdbe.org/6fjf PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6fjf RCSB], [http://www.ebi.ac.uk/pdbsum/6fjf PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6fjf ProSAT]</span></td></tr>
 </table>
 == 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;">
 == Publication Abstract from PubMed ==
@@ Line 22: / Line 21: @@
 ==See Also==
-*[[Stathmin|Stathmin]]
+*[[Stathmin-4 3D structures|Stathmin-4 3D structures]]
-*[[Tubulin tyrosine ligase|Tubulin tyrosine ligase]]
+*[[Tubulin 3D Structures|Tubulin 3D Structures]]
 == References ==
 <references/>
@@ Line 29: / Line 28: @@
 </StructureSection>
 [[Category: Bos taurus]]
-[[Category: Buffalo rat]]
+[[Category: Gallus gallus]]
-[[Category: Chick]]
+[[Category: Large Structures]]
-[[Category: Altmann, K H]]
+[[Category: Rattus norvegicus]]
-[[Category: Angell, D Lucena]]
+[[Category: Altmann K-H]]
-[[Category: Bucher, P]]
+[[Category: Bucher P]]
-[[Category: Diaz, J F]]
+[[Category: Diaz JF]]
-[[Category: Menchon, G]]
+[[Category: Lucena Angell D]]
-[[Category: Mueller, R]]
+[[Category: Menchon G]]
-[[Category: Paterson, I]]
+[[Category: Mueller R]]
-[[Category: Prota, A E]]
+[[Category: Paterson I]]
-[[Category: Steinmetz, M O]]
+[[Category: Prota AE]]
-[[Category: Cell cycle]]
+[[Category: Steinmetz MO]]
-[[Category: Cytoskeleton]]
-[[Category: Microtubule]]
-[[Category: Tubulin fold]]

6fjf: Difference between revisions

Latest revision as of 05:37, 23 April 2025

Tubulin-FcMaytansine complex

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

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