5GON

Structures of a beta-lactam bridged analogue in complex with tubulin

Summary for 5GON

• Entry DOI: 10.2210/pdb5gon/pdb
• Related: 4O2B
• Descriptor: Tubulin alpha-1B chain, 2-(N-MORPHOLINO)-ETHANESULFONIC ACID, (3R,4R)-4-(4-methoxy-3-oxidanyl-phenyl)-3-methyl-1-(3,4,5-trimethoxyphenyl)azetidin-2-one, ... (13 entities in total)
• Functional Keywords: beta-lactam bridged analogue tubulin colchicine binding site, structural protein
• Biological source: Gallus gallus (Chicken); More
• Cellular location: Cytoplasm, cytoskeleton: P81947 Q6B856; Golgi apparatus : P63043
• Total number of polymer chains: 6
• Total formula weight: 258402.97

Authors

Zhou, L.,Liu, Y.,Cheng, L.,Wang, Y. (deposition date: 2016-07-28, release date: 2017-03-22, Last modification date: 2024-03-20)

Primary citation

Zhou, P.,Liu, Y.,Zhou, L.,Zhu, K.,Feng, K.,Zhang, H.,Liang, Y.,Jiang, H.,Luo, C.,Liu, M.,Wang, Y.
Potent Antitumor Activities and Structure Basis of the Chiral beta-Lactam Bridged Analogue of Combretastatin A-4 Binding to Tubulin.
J. Med. Chem., 59:10329-10334, 2016

PubMed Abstract: A series of chiral β-lactam bridged analogues (3-substituted 1,4-diaryl-2-azetidinones) of combretastatin A-4 (CA-4) were synthesized asymmetrically, and their antitumor activities were evaluated in vitro and in vivo. The cocrystal structure of tubulin in complex with compound 9 was determined by X-ray crystallography, which showed that 9 binds to the same site as colchicine with similar binding mode, and the absolute configuration of its C-4 was first identified and demonstrated to be critically important for their antiproliferative activities.

PubMed: 27805821
DOI: 10.1021/acs.jmedchem.6b01268

Experimental method

X-RAY DIFFRACTION (2.48 Å)