5xlt

From Proteopedia

(Difference between revisions)

Revision as of 10:23, 27 September 2017

The crystal structure of tubulin in complex with 4'-demethylepipodophyllotoxin

Structural highlights

5xlt 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

Microtubules consists of alphabeta-tubulin heterodimers and are highly attractive targets for anti-cancer drugs. A broad range of agents have been identified to bind to tubulin and interfere with microtubule assembly, including colchicine binding site inhibitors (CBSIs). Podophyllotoxin is a CBSI that inhibits the assembly of microtubules. However, for a long time, the design and development of podophyllotoxin family drugs have been hindered by the lack of high-resolution structural information of the tubulin-agent complex. We report the first high-resolution (2.8 A) structure of a podophyllotoxin family agent (4'-demethylepipodophyllotoxin, DMEP) complexed with tubulin and revealed the detailed interactions between DMEP and tubulin. Comparison of this structure and other CBSIs explains previous results of the structure-activity-relationship (SAR) studies, and provides insights into the development of new podophyllotoxin derivatives targeting the colchicine site.

Structure of 4'-demethylepipodophyllotoxin in complex with tubulin provides a rationale for drug design.,Niu L, Wang Y, Wang C, Wang Y, Jiang X, Ma L, Wu C, Yu Y, Chen Q Biochem Biophys Res Commun. 2017 Aug 30. pii: S0006-291X(17)31708-4. doi:, 10.1016/j.bbrc.2017.08.125. PMID:28864414^[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
↑ Niu L, Wang Y, Wang C, Wang Y, Jiang X, Ma L, Wu C, Yu Y, Chen Q. Structure of 4'-demethylepipodophyllotoxin in complex with tubulin provides a rationale for drug design. Biochem Biophys Res Commun. 2017 Aug 30. pii: S0006-291X(17)31708-4. doi:, 10.1016/j.bbrc.2017.08.125. PMID:28864414 doi:http://dx.doi.org/10.1016/j.bbrc.2017.08.125

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/5xlt"

@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
-The entry 5xlt is ON HOLD
+==The crystal structure of tubulin in complex with 4'-demethylepipodophyllotoxin==
+<StructureSection load='5xlt' size='340' side='right' caption='[[5xlt]], [[Resolution|resolution]] 2.81&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[5xlt]] 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=5XLT OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5XLT FirstGlance]. <br>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=89O:(5S,5aR,8aR,9R)-9-(3,5-dimethoxy-4-oxidanyl-phenyl)-5-oxidanyl-5a,6,8a,9-tetrahydro-5H-[2]benzofuro[6,5-f][1,3]benzodioxol-8-one'>89O</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='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=5xlt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5xlt OCA], [http://pdbe.org/5xlt PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5xlt RCSB], [http://www.ebi.ac.uk/pdbsum/5xlt PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5xlt 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 ==
+Microtubules consists of alphabeta-tubulin heterodimers and are highly attractive targets for anti-cancer drugs. A broad range of agents have been identified to bind to tubulin and interfere with microtubule assembly, including colchicine binding site inhibitors (CBSIs). Podophyllotoxin is a CBSI that inhibits the assembly of microtubules. However, for a long time, the design and development of podophyllotoxin family drugs have been hindered by the lack of high-resolution structural information of the tubulin-agent complex. We report the first high-resolution (2.8 A) structure of a podophyllotoxin family agent (4'-demethylepipodophyllotoxin, DMEP) complexed with tubulin and revealed the detailed interactions between DMEP and tubulin. Comparison of this structure and other CBSIs explains previous results of the structure-activity-relationship (SAR) studies, and provides insights into the development of new podophyllotoxin derivatives targeting the colchicine site.
-Authors: Yu, Y., Chen, Q.
+Structure of 4'-demethylepipodophyllotoxin in complex with tubulin provides a rationale for drug design.,Niu L, Wang Y, Wang C, Wang Y, Jiang X, Ma L, Wu C, Yu Y, Chen Q Biochem Biophys Res Commun. 2017 Aug 30. pii: S0006-291X(17)31708-4. doi:, 10.1016/j.bbrc.2017.08.125. PMID:28864414<ref>PMID:28864414</ref>
-Description: The crystal structure of tubulin in complex with 4'-demethylepipodophyllotoxin
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
-[[Category: Yu, Y]]
+<div class="pdbe-citations 5xlt" style="background-color:#fffaf0;"></div>
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Bos taurus]]
 [[Category: Chen, Q]]
+[[Category: Yu, Y]]
+[[Category: Cell cycle]]
+[[Category: Inhibitor]]
+[[Category: Tubulin]]

5xlt

From Proteopedia

Revision as of 10:23, 27 September 2017

The crystal structure of tubulin in complex with 4'-demethylepipodophyllotoxin

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

Personal tools

Navigation

Search

Toolbox