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5la6

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Revision as of 07:04, 5 August 2020

Tubulin-pironetin complex

Structural highlights

5la6 is a 6 chain structure with sequence from [1] and Bos taurus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
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. [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

Microtubule-targeting agents are among the most powerful drugs used in chemotherapy to treat cancer patients. Pironetin is a natural product that displays promising anticancer properties by binding to and potently inhibiting tubulin assembly into microtubules; however, its molecular mechanism of action remained obscure. Here, we solved the crystal structure of the tubulin-pironetin complex and found that the compound covalently binds to Cys316 of alpha-tubulin. The structure further revealed that pironetin perturbs the T7 loop and helix H8 of alpha-tubulin. Since both these elements are essential for establishing longitudinal tubulin contacts in microtubules, this result explains how pironetin inhibits the formation of microtubules. Together, our data define the molecular details of the pironetin binding site on alpha-tubulin and thus offer a promising basis for the rational design of pironetin variants with improved activity profiles. They further extend our knowledge on strategies evolved by natural products to target and perturb the microtubule cytoskeleton.

Pironetin Binds Covalently to alphaCys316 and Perturbs a Major Loop and Helix of alpha-Tubulin to Inhibit Microtubule Formation.,Prota AE, Setter J, Waight AB, Bargsten K, Murga J, Diaz JF, Steinmetz MO J Mol Biol. 2016 Jul 6. pii: S0022-2836(16)30245-5. doi:, 10.1016/j.jmb.2016.06.023. PMID:27395016^[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, Setter J, Waight AB, Bargsten K, Murga J, Diaz JF, Steinmetz MO. Pironetin Binds Covalently to alphaCys316 and Perturbs a Major Loop and Helix of alpha-Tubulin to Inhibit Microtubule Formation. J Mol Biol. 2016 Jul 6. pii: S0022-2836(16)30245-5. doi:, 10.1016/j.jmb.2016.06.023. PMID:27395016 doi:http://dx.doi.org/10.1016/j.jmb.2016.06.023

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/5la6"

@@ Line 1: / Line 1: @@
 ==Tubulin-pironetin complex==
-<StructureSection load='5la6' size='340' side='right' caption='[[5la6]], [[Resolution|resolution]] 2.10&Aring;' scene=''>
+<StructureSection load='5la6' size='340' side='right'caption='[[5la6]], [[Resolution|resolution]] 2.10&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5la6]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/ ] and [http://en.wikipedia.org/wiki/Bos_taurus Bos taurus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5LA6 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5LA6 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5la6]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/ ] and [http://en.wikipedia.org/wiki/Bos_taurus Bos taurus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5LA6 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5LA6 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=GDP:GUANOSINE-5-DIPHOSPHATE'>GDP</scene>, <scene name='pdbligand=GTP:GUANOSINE-5-TRIPHOSPHATE'>GTP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=X3H:PIRONETIN'>X3H</scene></td></tr>
+</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=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=X3H:PIRONETIN'>X3H</scene></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=5la6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5la6 OCA], [http://pdbe.org/5la6 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5la6 RCSB], [http://www.ebi.ac.uk/pdbsum/5la6 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5la6 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=5la6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5la6 OCA], [http://pdbe.org/5la6 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5la6 RCSB], [http://www.ebi.ac.uk/pdbsum/5la6 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5la6 ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 20: / Line 20: @@
 ==See Also==
-*[[Stathmin|Stathmin]]
+*[[Stathmin-4 3D structures|Stathmin-4 3D structures]]
-*[[Tubulin|Tubulin]]
+*[[Tubulin 3D Structures|Tubulin 3D Structures]]
 *[[Tubulin tyrosine ligase|Tubulin tyrosine ligase]]
+*[[User:Alisa Cario|User:Alisa Cario]]
 == References ==
 <references/>
@@ Line 28: / Line 29: @@
 </StructureSection>
 [[Category: Bos taurus]]
+[[Category: Large Structures]]
 [[Category: Bargsten, K]]
 [[Category: Diaz, J F]]

5la6

From Proteopedia

Revision as of 07:04, 5 August 2020

Tubulin-pironetin complex

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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