6jcj

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Structure of crolibulin in complex with tubulin

Structural highlights

6jcj is a 6 chain structure with sequence from Bos taurus, Gallus gallus, Rattus norvegicus and Sus scrofa. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2.5Å
Ligands:ACP, BG0, CA, GDP, GTP, MG
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

TBA1B_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

Microtubules (MTs) is one of the most important proteins in eukaryotic cells and plays a key role in the maintenance of cell morphology and cell division. The discovery and development of small molecule drugs targeting MTs has always been an important direction of anti-cancer research. Nowadays 4-Aryl-4H-chromenes have emerged as potent microtubule-targeting agents (MTAs) for various cancers. Crolibulin, a derivative of 4-Aryl-4H-chromenes, which has been progressed to Phase I/II clinical testing's for anaplastic thyroid cancer with the National Cancer Institute. However, the design and development of 4-Aryl-4H-chromenes family drugs have been hindered for a long time by the lack of structural information of the tubulin-agent complex. Here we report a 2.5A crystal structure of tubulin complexed with crolibulin. This complex structure reveals the interactions between crolibulin and tubulin, helps explain the results of the structure-activity-relationship (SAR) studies and provides a solid structural basis for the design and development of new 4-Aryl-4H-chromenes derivatives as MTAs.

Molecular mechanism of crolibulin in complex with tubulin provides a rationale for drug design.,Zhang Z, Wang C, Ma L, Jiang X, Wu C, Wang Y, Jiang Y, Zheng W, Yang Y, Ma Y, Yang J Biochem Biophys Res Commun. 2019 Apr 2;511(2):381-386. doi:, 10.1016/j.bbrc.2019.02.064. Epub 2019 Feb 22. PMID:30803758[1]

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

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Citations
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Synthesis and Antiproliferative Evaluation of 3-Chloroazetidin-2-ones with Antimitotic Activity: Heterocyclic Bridged Analogues of Combretastatin A-4.
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See Also

References

  1. ↑ Zhang Z, Wang C, Ma L, Jiang X, Wu C, Wang Y, Jiang Y, Zheng W, Yang Y, Ma Y, Yang J. Molecular mechanism of crolibulin in complex with tubulin provides a rationale for drug design. Biochem Biophys Res Commun. 2019 Apr 2;511(2):381-386. doi:, 10.1016/j.bbrc.2019.02.064. Epub 2019 Feb 22. PMID:30803758 doi:http://dx.doi.org/10.1016/j.bbrc.2019.02.064

Contents


PDB ID 6jcj

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OCA

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