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5syg

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Revision as of 21:34, 10 April 2020

Cryo-EM reconstruction of zampanolide-bound microtubule

5syg, resolution 3.50Å

Structural highlights

5syg is a 2 chain structure with sequence from Sus scrofa. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Related:	5syc, 5sye, 5syf
Experimental data:	Check to display Experimental Data
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[B6A7R0_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.[RuleBase:RU000352][SAAS:SAAS00540896] [TBB_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

A number of microtubule (MT)-stabilizing agents (MSAs) have demonstrated or predicted potential as anticancer agents, but a detailed structural basis for their mechanism of action is still lacking. We have obtained high-resolution (3.9-4.2A) cryo-electron microscopy (cryo-EM) reconstructions of MTs stabilized by the taxane-site binders Taxol and zampanolide, and by peloruside, which targets a distinct, non-taxoid pocket on beta-tubulin. We find that each molecule has unique distinct structural effects on the MT lattice structure. Peloruside acts primarily at lateral contacts and has an effect on the "seam" of heterologous interactions, enforcing a conformation more similar to that of homologous (i.e., non-seam) contacts by which it regularizes the MT lattice. In contrast, binding of either Taxol or zampanolide induces MT heterogeneity. In doubly bound MTs, peloruside overrides the heterogeneity induced by Taxol binding. Our structural analysis illustrates distinct mechanisms of these drugs for stabilizing the MT lattice and is of relevance to the possible use of combinations of MSAs to regulate MT activity and improve therapeutic potential.

Insights into the Distinct Mechanisms of Action of Taxane and Non-Taxane Microtubule Stabilizers from Cryo-EM Structures.,Kellogg EH, Hejab NM, Howes S, Northcote P, Miller JH, Diaz JF, Downing KH, Nogales E J Mol Biol. 2017 Jan 17. pii: S0022-2836(17)30015-3. doi:, 10.1016/j.jmb.2017.01.001. PMID:28104363^[1]

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

References

↑ Kellogg EH, Hejab NM, Howes S, Northcote P, Miller JH, Diaz JF, Downing KH, Nogales E. Insights into the Distinct Mechanisms of Action of Taxane and Non-Taxane Microtubule Stabilizers from Cryo-EM Structures. J Mol Biol. 2017 Jan 17. pii: S0022-2836(17)30015-3. doi:, 10.1016/j.jmb.2017.01.001. PMID:28104363 doi:http://dx.doi.org/10.1016/j.jmb.2017.01.001

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/5syg"

@@ Line 3: / Line 3: @@
 <SX load='5syg' size='340' side='right' viewer='molstar' caption='[[5syg]], [[Resolution|resolution]] 3.50&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5syg]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Sus_scrofa Sus scrofa]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5SYG OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5SYG FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5syg]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Sus_scrofa Sus scrofa]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5SYG OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5SYG FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><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=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>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><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=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">[[5syc|5syc]], [[5sye|5sye]], [[5syf|5syf]]</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=5syg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5syg OCA], [http://pdbe.org/5syg PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5syg RCSB], [http://www.ebi.ac.uk/pdbsum/5syg PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5syg 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=5syg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5syg OCA], [http://pdbe.org/5syg PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5syg RCSB], [http://www.ebi.ac.uk/pdbsum/5syg PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5syg ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 19: / Line 19: @@
 </div>
 <div class="pdbe-citations 5syg" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Tubulin 3D Structures|Tubulin 3D Structures]]
 == References ==
 <references/>

5syg

From Proteopedia

Revision as of 21:34, 10 April 2020

Cryo-EM reconstruction of zampanolide-bound microtubule

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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