5JQG
An apo tubulin-RB-TTL complex structure used for side-by-side comparison
Summary for 5JQG
| Entry DOI | 10.2210/pdb5jqg/pdb |
| Related | 5fnv |
| Descriptor | Tubulin alpha-1B chain, 2-(N-MORPHOLINO)-ETHANESULFONIC ACID, PHOSPHOMETHYLPHOSPHONIC ACID ADENYLATE ESTER, ... (12 entities in total) |
| Functional Keywords | apo structure, structural protein |
| Biological source | Rattus norvegicus (Rat) More |
| Cellular location | Cytoplasm, cytoskeleton: Q2XVP4 P02554 Golgi apparatus : P63043 |
| Total number of polymer chains | 6 |
| Total formula weight | 264608.42 |
| Authors | Wang, Y.X.,Naismith, J.H.,Zhu, X. (deposition date: 2016-05-04, release date: 2016-05-18, Last modification date: 2023-11-08) |
| Primary citation | Yang, J.,Wang, Y.X.,Wang, T.,Jiang, J.,Botting, C.H.,Liu, H.,Chen, Q.,Yang, J.,Naismith, J.H.,Zhu, X.,Chen, L. Pironetin reacts covalently with cysteine-316 of alpha-tubulin to destabilize microtubule Nat Commun, 7:12103-12103, 2016 Cited by PubMed Abstract: Molecules that alter the normal dynamics of microtubule assembly and disassembly include many anticancer drugs in clinical use. So far all such therapeutics target β-tubulin, and structural biology has explained the basis of their action and permitted design of new drugs. However, by shifting the profile of β-tubulin isoforms, cancer cells become resistant to treatment. Compounds that bind to α-tubulin are less well characterized and unexploited. The natural product pironetin is known to bind to α-tubulin and is a potent inhibitor of microtubule polymerization. Previous reports had identified that pironetin reacts with lysine-352 residue however analogues designed on this model had much lower potency, which was difficult to explain, hindering further development. We report crystallographic and mass spectrometric data that reveal that pironetin forms a covalent bond to cysteine-316 in α-tubulin via a Michael addition reaction. These data provide a basis for the rational design of α-tubulin targeting chemotherapeutics. PubMed: 27357539DOI: 10.1038/ncomms12103 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.24 Å) |
Structure validation
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