5lxs

From Proteopedia

(Difference between revisions)

Revision as of 04:31, 21 September 2017

Tubulin-KS-1-199-32 complex

Structural highlights

5lxs 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:	, , , , , ,
Related:	4i4t, 4i50, 5lxt
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 widely used in chemotherapy. Here, using X-ray crystallography we describe the detailed binding modes of two potent MSAs, (+)-discodermolide (DDM) and the DDM-paclitaxel-hybrid KS-1-199-32, in the taxane pocket of ss-tubulin. Both compounds bind in a very similar hairpin conformation as previously observed in solution. However, they differentially stabilize the M-loop of ss-tubulin: KS-1-199-32 induces an M-loop helical conformation that is not observed for DDM. In the context of the microtubule structure, both MSAs connect the ss-tubulin helices H6 and H7 and loop S9-S10 with the M-loop, which is similar to the structural effects elicited by epothilone A, but distinct from paclitaxel. Together, our data rationalize a differential binding mechanism of DDM and KS-1-199-32 on tubulin.

Structural Basis of Microtubule Stabilization by Discodermolide.,Prota AE, Bargsten K, Redondo M, Smith Iii AB, Yang CH, McDaid HM, Paterson I, Horwitz SB, Diaz JF, Steinmetz MO Chembiochem. 2017 Feb 16. doi: 10.1002/cbic.201600696. PMID:28207984^[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, Redondo M, Smith Iii AB, Yang CH, McDaid HM, Paterson I, Horwitz SB, Diaz JF, Steinmetz MO. Structural Basis of Microtubule Stabilization by Discodermolide. Chembiochem. 2017 Feb 16. doi: 10.1002/cbic.201600696. PMID:28207984 doi:http://dx.doi.org/10.1002/cbic.201600696

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/5lxs"

@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
-The entry 5lxs is ON HOLD
+==Tubulin-KS-1-199-32 complex==
+<StructureSection load='5lxs' size='340' side='right' caption='[[5lxs]], [[Resolution|resolution]] 2.20&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[5lxs]] 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=5LXS OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5LXS FirstGlance]. <br>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=7AO:[(3~{Z},5~{S},6~{S},7~{S},8~{R},9~{S},11~{Z},13~{S},14~{S},15~{S},16~{Z},18~{S})-19-[(2~{S},3~{R},4~{S},5~{R})-3,5-dimethyl-4-oxidanyl-6-oxidanylidene-oxan-2-yl]-5,7,9,11,13,15-hexamethyl-8,14,18-tris(oxidanyl)nonadeca-1,3,11,16-tetraen-6-yl]+~{N}-[3-[(3-azidophenyl)carbonylamino]propyl]carbamate'>7AO</scene>, <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=MES:2-(N-MORPHOLINO)-ETHANESULFONIC+ACID'>MES</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr>
+<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4i4t|4i4t]], [[4i50|4i50]], [[5lxt|5lxt]]</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=5lxs FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5lxs OCA], [http://pdbe.org/5lxs PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5lxs RCSB], [http://www.ebi.ac.uk/pdbsum/5lxs PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5lxs 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).
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Microtubule-stabilizing agents (MSAs) are widely used in chemotherapy. Here, using X-ray crystallography we describe the detailed binding modes of two potent MSAs, (+)-discodermolide (DDM) and the DDM-paclitaxel-hybrid KS-1-199-32, in the taxane pocket of ss-tubulin. Both compounds bind in a very similar hairpin conformation as previously observed in solution. However, they differentially stabilize the M-loop of ss-tubulin: KS-1-199-32 induces an M-loop helical conformation that is not observed for DDM. In the context of the microtubule structure, both MSAs connect the ss-tubulin helices H6 and H7 and loop S9-S10 with the M-loop, which is similar to the structural effects elicited by epothilone A, but distinct from paclitaxel. Together, our data rationalize a differential binding mechanism of DDM and KS-1-199-32 on tubulin.
-Authors: Prota, A.E., Steinmetz, M.O.
+Structural Basis of Microtubule Stabilization by Discodermolide.,Prota AE, Bargsten K, Redondo M, Smith Iii AB, Yang CH, McDaid HM, Paterson I, Horwitz SB, Diaz JF, Steinmetz MO Chembiochem. 2017 Feb 16. doi: 10.1002/cbic.201600696. PMID:28207984<ref>PMID:28207984</ref>
-Description: Tubulin-drug2 complex
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
-[[Category: Prota, A.E]]
+<div class="pdbe-citations 5lxs" style="background-color:#fffaf0;"></div>
-[[Category: Steinmetz, M.O]]
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Bos taurus]]
+[[Category: Prota, A E]]
+[[Category: Steinmetz, M O]]
+[[Category: Cell cycle]]
+[[Category: Cytoskeleton]]
+[[Category: Discodermolide]]
+[[Category: Microtubule]]
+[[Category: Tubulin fold]]

5lxs

From Proteopedia

Revision as of 04:31, 21 September 2017

Tubulin-KS-1-199-32 complex

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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