| 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.
See Also
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
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