4o4l

From Proteopedia

(Difference between revisions)

Revision as of 13:24, 5 August 2016

Tubulin-Peloruside A-Epothilone A complex

Structural highlights

4o4l is a 6 chain structure with sequence from Bos taurus, Buffalo rat and Chick. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	, , , , , ,
Related:	4o4h, 4o4i, 4o4j
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. [STMN4_RAT] Exhibits microtubule-destabilizing activity.^[1] ^[2] ^[3] [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).

Publication Abstract from PubMed

Laulimalide and peloruside A are microtubule-stabilizing agents (MSAs), the mechanism of action on microtubules of which is poorly defined. Here, using X-ray crystallography it is shown that laulimalide and peloruside A bind to a unique non-taxane site on beta-tubulin and use their respective macrolide core structures to interact with a second tubulin dimer across protofilaments. At the same time, they allosterically stabilize the taxane-site M-loop that establishes lateral tubulin contacts in microtubules. Structures of ternary complexes of tubulin with laulimalide/peloruside A and epothilone A are also solved, and a crosstalk between the laulimalide/peloruside and taxane sites via the M-loop of beta-tubulin is found. Together, the data define the mechanism of action of laulimalide and peloruside A on tubulin and microtubules. The data further provide a structural framework for understanding the synergy observed between two classes of MSAs in tubulin assembly and the inhibition of cancer cell growth.

Structural basis of microtubule stabilization by laulimalide and peloruside a.,Prota AE, Bargsten K, Northcote PT, Marsh M, Altmann KH, Miller JH, Diaz JF, Steinmetz MO Angew Chem Int Ed Engl. 2014 Feb 3;53(6):1621-5. doi: 10.1002/anie.201307749., Epub 2014 Jan 27. PMID:24470331^[4]

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

References

↑ Nakao C, Itoh TJ, Hotani H, Mori N. Modulation of the stathmin-like microtubule destabilizing activity of RB3, a neuron-specific member of the SCG10 family, by its N-terminal domain. J Biol Chem. 2004 May 28;279(22):23014-21. Epub 2004 Mar 22. PMID:15039434 doi:http://dx.doi.org/10.1074/jbc.M313693200
↑ Gavet O, El Messari S, Ozon S, Sobel A. Regulation and subcellular localization of the microtubule-destabilizing stathmin family phosphoproteins in cortical neurons. J Neurosci Res. 2002 Jun 1;68(5):535-50. PMID:12111843 doi:http://dx.doi.org/10.1002/jnr.10234
↑ Ravelli RB, Gigant B, Curmi PA, Jourdain I, Lachkar S, Sobel A, Knossow M. Insight into tubulin regulation from a complex with colchicine and a stathmin-like domain. Nature. 2004 Mar 11;428(6979):198-202. PMID:15014504 doi:http://dx.doi.org/10.1038/nature02393
↑ Prota AE, Bargsten K, Northcote PT, Marsh M, Altmann KH, Miller JH, Diaz JF, Steinmetz MO. Structural basis of microtubule stabilization by laulimalide and peloruside a. Angew Chem Int Ed Engl. 2014 Feb 3;53(6):1621-5. doi: 10.1002/anie.201307749., Epub 2014 Jan 27. PMID:24470331 doi:http://dx.doi.org/10.1002/anie.201307749

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 See Also
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4o4l"

@@ Line 1: / Line 1: @@
 ==Tubulin-Peloruside A-Epothilone A complex==
 <StructureSection load='4o4l' size='340' side='right' caption='[[4o4l]], [[Resolution|resolution]] 2.20&Aring;' scene=''>
@@ Line 5: / Line 6: @@
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=EP:EPOTHILONE+A'>EP</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=POU:PELORUSIDE+A'>POU</scene></td></tr>
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4o4h|4o4h]], [[4o4i|4o4i]], [[4o4j|4o4j]]</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=4o4l FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4o4l OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4o4l RCSB], [http://www.ebi.ac.uk/pdbsum/4o4l PDBsum]</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=4o4l FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4o4l OCA], [http://pdbe.org/4o4l PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4o4l RCSB], [http://www.ebi.ac.uk/pdbsum/4o4l PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4o4l ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 17: / Line 18: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 4o4l" style="background-color:#fffaf0;"></div>
 ==See Also==
+*[[Stathmin|Stathmin]]
 *[[Tubulin|Tubulin]]
+*[[Tubulin tyrosine ligase|Tubulin tyrosine ligase]]
 == References ==
 <references/>

4o4l

From Proteopedia

Revision as of 13:24, 5 August 2016

Tubulin-Peloruside A-Epothilone A complex

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

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