6MGO
Structure of rabbit actin in complex with Mycalolide B
Summary for 6MGO
| Entry DOI | 10.2210/pdb6mgo/pdb |
| Descriptor | Actin, alpha skeletal muscle, Mycalolide B, CALCIUM ION, ... (5 entities in total) |
| Functional Keywords | actin, natural product, structural protein |
| Biological source | Oryctolagus cuniculus (Rabbit) |
| Total number of polymer chains | 1 |
| Total formula weight | 43625.47 |
| Authors | Allingham, J.S.,Trofimova, D. (deposition date: 2018-09-14, release date: 2018-11-21, Last modification date: 2023-10-11) |
| Primary citation | Pipaliya, B.V.,Trofimova, D.N.,Grange, R.L.,Aeluri, M.,Deng, X.,Shah, K.,Craig, A.W.,Allingham, J.S.,Evans, P.A. Truncated Actin-Targeting Macrolide Derivative Blocks Cancer Cell Motility and Invasion of Extracellular Matrix. J.Am.Chem.Soc., 2021 Cited by PubMed Abstract: Cancer metastasis is a complex process involving highly motile tumor cells that breach tissue barriers, enter the bloodstream and lymphatic system, and disseminate throughout the body as circulating tumor cells. The primary cellular mechanism contributing to these critical events is the reorganization of the actin cytoskeleton. Mycalolide B (MycB) is an actin-targeting marine macrolide that can suppress proliferation, migration, and invasion of breast and ovarian cancer cells at low nanomolar doses. Through structure-activity relationship studies focused on the actin-binding tail region (C24-C35) of MycB, we identified a potent truncated derivative that inhibits polymerization of G-actin and severs F-actin by binding to actin's barbed end cleft. Biological analyses of this miniature MycB derivative demonstrate that it causes a rapid collapse of the actin cytoskeleton in ovarian cancer cells and impairs cancer cell motility and invasion of the extracellular matrix (ECM) by inhibiting invadopodia-mediated ECM degradation. These studies provide essential proof-of-principle for developing actin-targeting therapeutic agents to block cancer metastasis and establish a synthetically tractable barbed end-binding pharmacophore that can be further improved by adding targeting groups for precision drug design. PubMed: 33938740DOI: 10.1021/jacs.0c12404 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.2 Å) |
Structure validation
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