5KX5

Crystal structure of tubulin-stathmin-TTL-Compound 11 complex

Summary for 5KX5

• Entry DOI: 10.2210/pdb5kx5/pdb
• Descriptor: Tubulin alpha chain, ADENOSINE-5'-DIPHOSPHATE, Tubulin beta chain, ... (11 entities in total)
• Functional Keywords: tubulin tubulysin, structural protein-inhibitor complex, structural protein/inhibitor
• Biological source: Rattus norvegicus (Rat); More
• Cellular location: Cytoplasm, cytoskeleton : D0VWZ0 D0VWY9; Golgi apparatus : P63043
• Total number of polymer chains: 6
• Total formula weight: 265698.15

Authors

Parris, K. (deposition date: 2016-07-20, release date: 2016-12-28, Last modification date: 2023-10-04)

Primary citation

Leverett, C.A.,Sukuru, S.C.,Vetelino, B.C.,Musto, S.,Parris, K.,Pandit, J.,Loganzo, F.,Varghese, A.H.,Bai, G.,Liu, B.,Liu, D.,Hudson, S.,Doppalapudi, V.R.,Stock, J.,O'Donnell, C.J.,Subramanyam, C.
Design, Synthesis, and Cytotoxic Evaluation of Novel Tubulysin Analogues as ADC Payloads.
ACS Med Chem Lett, 7:999-1004, 2016

PubMed Abstract: The tubulysin class of natural products has attracted much attention from the medicinal chemistry community due to its potent cytotoxicity against a wide range of human cancer cell lines, including significant activity in multidrug-resistant carcinoma models. As a result of their potency, the tubulysins have become an important tool for use in targeted therapy, being widely pursued as payloads in the development of novel small molecule drug conjugates (SMDCs) and antibody-drug conjugates (ADCs). A structure-based and parallel medicinal chemistry approach was applied to the synthesis of novel tubulysin analogues. These efforts led to the discovery of a number of novel and potent cytotoxic tubulysin analogues, providing a framework for our simultaneous report, which highlights the discovery of tubulysin-based ADCs, including use of site-specific conjugation to address in vivo stability of the C-11 acetate functionality.

PubMed: 27882198
DOI: 10.1021/acsmedchemlett.6b00274

Experimental method

X-RAY DIFFRACTION (2.5 Å)