6gj4: Difference between revisions

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'''Unreleased structure'''


The entry 6gj4 is ON HOLD
==Tubulin-6j complex==
<StructureSection load='6gj4' size='340' side='right' caption='[[6gj4]], [[Resolution|resolution]] 2.40&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6gj4]] 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=6GJ4 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6GJ4 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=EZW:5-(quinolin-5-yl)naphtho[2,3-b]pyrrolo[1,2-d][1,4]oxazepin-4-yl+acetate'>EZW</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=6gj4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6gj4 OCA], [http://pdbe.org/6gj4 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6gj4 RCSB], [http://www.ebi.ac.uk/pdbsum/6gj4 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6gj4 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-targeting agents (MTAs) are a class of clinically successful anti-cancer drugs. The emergence of multidrug resistance to MTAs imposes the need for developing new MTAs endowed with diverse mechanistic properties. Benzoxazepines were recently identified as a novel class of MTAs. These anticancer agents were thoroughly characterized for their antitumor activity, although, their exact mechanism of action remained elusive. Combining chemical, biochemical, cellular, bioinformatics and structural efforts we developed improved pyrrolonaphthoxazepines antitumor agents and their mode of action at the molecular level was elucidated. Compound 6j, one of the most potent analogues, was confirmed by X-ray as a colchicine-site MTA. A comprehensive structural investigation was performed for a complete elucidation of the structure-activity relationships. Selected pyrrolonaphthoxazepines were evaluated for their effects on cell cycle, apoptosis and differentiation in a variety of cancer cells, including multidrug resistant cell lines. Our results define compound 6j as a potentially useful optimized hit for the development of effective compounds for treating drug-resistant tumors.


Authors:  
Structure-activity relationships, biological evaluation and structural studies of novel pyrrolonaphthoxazepines as antitumor agents.,Brindisi M, Ulivieri C, Alfano G, Gemma S, de Asis Balaguer F, Khan T, Grillo A, Chemi G, Menchon G, Prota AE, Olieric N, Lucena-Agell D, Barasoain I, Diaz JF, Nebbioso A, Conte M, Lopresti L, Magnano S, Amet R, Kinsella P, Zisterer DM, Ibrahim O, O'Sullivan J, Morbidelli L, Spaccapelo R, Baldari C, Butini S, Novellino E, Campiani G, Altucci L, Steinmetz MO, Brogi S Eur J Med Chem. 2018 Nov 3;162:290-320. doi: 10.1016/j.ejmech.2018.11.004. PMID:30448418<ref>PMID:30448418</ref>


Description:  
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
[[Category: Unreleased Structures]]
</div>
<div class="pdbe-citations 6gj4" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Bos taurus]]
[[Category: Agell, D L]]
[[Category: Alfano, G]]
[[Category: Altucci, L]]
[[Category: Amet, R]]
[[Category: Balaguer, F d.A]]
[[Category: Baldari, C]]
[[Category: Barasoain, I]]
[[Category: Brindisi, M]]
[[Category: Brogi, S]]
[[Category: Butini, S]]
[[Category: Campiani, G]]
[[Category: Chemi, G]]
[[Category: Conte, M R]]
[[Category: Diaz, J F]]
[[Category: Gemma, S]]
[[Category: Grillo, A]]
[[Category: Ibrahim, O]]
[[Category: Khan, T]]
[[Category: Kinsella, P]]
[[Category: Lopresti, L]]
[[Category: Magnano, S]]
[[Category: Menchon, G]]
[[Category: Morbidelli, L]]
[[Category: Nebbioso, A]]
[[Category: Novellino, E]]
[[Category: Olieric, N]]
[[Category: Prota, A E]]
[[Category: Spaccapelo, R]]
[[Category: Steinmetz, M O]]
[[Category: Sullivan, J O]]
[[Category: Ulivieri, C]]
[[Category: Zisterer, D M]]
[[Category: Cell cycle]]
[[Category: Cytoskeleton]]
[[Category: Microtubule]]
[[Category: Tubulin fold]]

Latest revision as of 09:38, 5 December 2018

Tubulin-6j complexTubulin-6j complex

Structural highlights

6gj4 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 (MTAs) are a class of clinically successful anti-cancer drugs. The emergence of multidrug resistance to MTAs imposes the need for developing new MTAs endowed with diverse mechanistic properties. Benzoxazepines were recently identified as a novel class of MTAs. These anticancer agents were thoroughly characterized for their antitumor activity, although, their exact mechanism of action remained elusive. Combining chemical, biochemical, cellular, bioinformatics and structural efforts we developed improved pyrrolonaphthoxazepines antitumor agents and their mode of action at the molecular level was elucidated. Compound 6j, one of the most potent analogues, was confirmed by X-ray as a colchicine-site MTA. A comprehensive structural investigation was performed for a complete elucidation of the structure-activity relationships. Selected pyrrolonaphthoxazepines were evaluated for their effects on cell cycle, apoptosis and differentiation in a variety of cancer cells, including multidrug resistant cell lines. Our results define compound 6j as a potentially useful optimized hit for the development of effective compounds for treating drug-resistant tumors.

Structure-activity relationships, biological evaluation and structural studies of novel pyrrolonaphthoxazepines as antitumor agents.,Brindisi M, Ulivieri C, Alfano G, Gemma S, de Asis Balaguer F, Khan T, Grillo A, Chemi G, Menchon G, Prota AE, Olieric N, Lucena-Agell D, Barasoain I, Diaz JF, Nebbioso A, Conte M, Lopresti L, Magnano S, Amet R, Kinsella P, Zisterer DM, Ibrahim O, O'Sullivan J, Morbidelli L, Spaccapelo R, Baldari C, Butini S, Novellino E, Campiani G, Altucci L, Steinmetz MO, Brogi S Eur J Med Chem. 2018 Nov 3;162:290-320. doi: 10.1016/j.ejmech.2018.11.004. PMID:30448418[4]

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

References

  1. ↑ 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
  2. ↑ 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
  3. ↑ 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
  4. ↑ Brindisi M, Ulivieri C, Alfano G, Gemma S, de Asis Balaguer F, Khan T, Grillo A, Chemi G, Menchon G, Prota AE, Olieric N, Lucena-Agell D, Barasoain I, Diaz JF, Nebbioso A, Conte M, Lopresti L, Magnano S, Amet R, Kinsella P, Zisterer DM, Ibrahim O, O'Sullivan J, Morbidelli L, Spaccapelo R, Baldari C, Butini S, Novellino E, Campiani G, Altucci L, Steinmetz MO, Brogi S. Structure-activity relationships, biological evaluation and structural studies of novel pyrrolonaphthoxazepines as antitumor agents. Eur J Med Chem. 2018 Nov 3;162:290-320. doi: 10.1016/j.ejmech.2018.11.004. PMID:30448418 doi:http://dx.doi.org/10.1016/j.ejmech.2018.11.004

6gj4, resolution 2.40Å

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