5LXS

Tubulin-KS-1-199-32 complex

Summary for 5LXS

• Entry DOI: 10.2210/pdb5lxs/pdb
• Related: 4I4T 4I50 5LXT
• Descriptor: Tubulin alpha-1B chain, 2-(N-MORPHOLINO)-ETHANESULFONIC ACID, PHOSPHOMETHYLPHOSPHONIC ACID ADENYLATE ESTER, ... (12 entities in total)
• Functional Keywords: cell cycle, tubulin fold, cytoskeleton, microtubule, discodermolide
• Biological source: Rattus norvegicus (Norway Rat); More
• Cellular location: Cytoplasm, cytoskeleton: P81947 Q6B856; Golgi apparatus : P63043
• Total number of polymer chains: 6
• Total formula weight: 266138.37

Authors

Prota, A.E.,Steinmetz, M.O. (deposition date: 2016-09-22, release date: 2017-09-20, Last modification date: 2024-01-17)

Primary citation

Prota, A.E.,Bargsten, K.,Redondo-Horcajo, M.,Smith, A.B.,Yang, C.H.,McDaid, H.M.,Paterson, I.,Horwitz, S.B.,Fernando Diaz, J.,Steinmetz, M.O.
Structural Basis of Microtubule Stabilization by Discodermolide.
Chembiochem, 18:905-909, 2017

PubMed Abstract: Microtubule-stabilizing agents (MSAs) are widely used in chemotherapy. Using X-ray crystallography we elucidated the detailed binding modes of two potent MSAs, (+)-discodermolide (DDM) and the DDM-paclitaxel hybrid KS-1-199-32, in the taxane pocket of β-tubulin. The two compounds bind in a very similar hairpin conformation, as previously observed in solution. However, they stabilize the M-loop of β-tubulin differently: KS-1-199-32 induces an M-loop helical conformation that is not observed for DDM. In the context of the microtubule structure, both MSAs connect the β-tubulin helices H6 and H7 and loop S9-S10 with the M-loop. This is similar to the structural effects elicited by epothilone A, but distinct from paclitaxel. Together, our data reveal differential binding mechanisms of DDM and KS-1-199-32 on tubulin.

PubMed: 28207984
DOI: 10.1002/cbic.201600696

Experimental method

X-RAY DIFFRACTION (2.2 Å)