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4i4t

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Revision as of 04:52, 5 August 2016

Crystal structure of tubulin-RB3-TTL-Zampanolide complex

Structural highlights

4i4t 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:	4i50, 4i55, 4ihj, 4iij
Gene:	Stmn4 (Buffalo rat), TTL (CHICK)
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-stabilizing agents (MSAs) are efficacious chemotherapeutic drugs widely used for the treatment of cancer. Despite the importance of MSAs for medical applications and basic research, their molecular mechanisms of action on tubulin and microtubules remain elusive. Here, we determined high-resolution crystal structures of alphabeta-tubulin in complex with two unrelated MSAs, zampanolide and epothilone A. Both compounds were bound to the taxane-pocket of beta-tubulin and used their respective side chain to induce structuring of the M-loop into a short helix. Because the M-loop establishes lateral tubulin contacts in microtubules, these findings explain how taxane-site MSAs promote microtubule assembly and stability. They further offer fundamental structural insights into the control mechanisms of microtubule dynamics.

Molecular Mechanism of Action of Microtubule-Stabilizing Anticancer Agents.,Prota AE, Bargsten K, Zurwerra D, Field JJ, Diaz JF, Altmann KH, Steinmetz MO Science. 2013 Jan 3. PMID:23287720^[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, Zurwerra D, Field JJ, Diaz JF, Altmann KH, Steinmetz MO. Molecular Mechanism of Action of Microtubule-Stabilizing Anticancer Agents. Science. 2013 Jan 3. PMID:23287720 doi:http://dx.doi.org/10.1126/science.1230582

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/4i4t"

@@ Line 1: / Line 1: @@
 ==Crystal structure of tubulin-RB3-TTL-Zampanolide complex==
 <StructureSection load='4i4t' size='340' side='right' caption='[[4i4t]], [[Resolution|resolution]] 1.80&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[4i4t]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/Bos_taurus Bos taurus], [http://en.wikipedia.org/wiki/Gallus_gallus Gallus gallus] and [http://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4I4T OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4I4T FirstGlance]. <br>
+<table><tr><td colspan='2'>[[4i4t]] 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=4I4T OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4I4T 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=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=GDP:GUANOSINE-5-DIPHOSPHATE'>GDP</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</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=TYR:TYROSINE'>TYR</scene>, <scene name='pdbligand=ZPN:(2Z,4E)-N-[(S)-[(1S,2E,5S,8E,10Z,17S)-3,11-DIMETHYL-19-METHYLIDENE-7,13-DIOXO-6,21-DIOXABICYCLO[15.3.1]HENICOSA-2,8,10-TRIEN-5-YL](HYDROXY)METHYL]HEXA-2,4-DIENAMIDE'>ZPN</scene></td></tr>
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4i50|4i50]], [[4i55|4i55]], [[4ihj|4ihj]], [[4iij|4iij]]</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 Rattus norvegicus]), TTL ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9031 Gallus gallus])</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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4i4t FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4i4t OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4i4t RCSB], [http://www.ebi.ac.uk/pdbsum/4i4t 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=4i4t FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4i4t OCA], [http://pdbe.org/4i4t PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4i4t RCSB], [http://www.ebi.ac.uk/pdbsum/4i4t PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4i4t ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 18: / Line 19: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 4i4t" style="background-color:#fffaf0;"></div>
 ==See Also==
+*[[Stathmin|Stathmin]]
 *[[Tubulin|Tubulin]]
+*[[Tubulin tyrosine ligase|Tubulin tyrosine ligase]]
 == References ==
 <references/>
@@ Line 26: / Line 30: @@
 </StructureSection>
 [[Category: Bos taurus]]
-[[Category: Gallus gallus]]
+[[Category: Buffalo rat]]
-[[Category: Rattus norvegicus]]
+[[Category: Chick]]
 [[Category: Prota, A E]]
 [[Category: Steinmetz, M O]]

4i4t

From Proteopedia

Revision as of 04:52, 5 August 2016

Crystal structure of tubulin-RB3-TTL-Zampanolide complex

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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