1WUA

The structure of Aplyronine A-actin complex

Summary for 1WUA

• Entry DOI: 10.2210/pdb1wua/pdb
• Descriptor: Actin, alpha skeletal muscle, CALCIUM ION, ADENOSINE-5'-TRIPHOSPHATE, ... (5 entities in total)
• Functional Keywords: aplyronine a, macrolide, potent antitumor effect, marine sponge, structural protein
• Biological source: Oryctolagus cuniculus (rabbit)
• Cellular location: Cytoplasm, cytoskeleton: P68135
• Total number of polymer chains: 1
• Total formula weight: 43499.34

Authors

Hirata, K.,Muraoka, S.,Suenaga, K.,Kuroda, T.,Kato, K.,Tanaka, H.,Yamamoto, M.,Takata, M.,Yamada, K.,Kigoshi, H. (deposition date: 2004-12-03, release date: 2006-02-14, Last modification date: 2023-10-25)

Primary citation

Hirata, K.,Muraoka, S.,Suenaga, K.,Kuroda, T.,Kato, K.,Tanaka, H.,Yamamoto, M.,Takata, M.,Yamada, K.,Kigoshi, H.
Structure basis for antitumor effect of aplyronine a
J.Mol.Biol., 356:945-954, 2006

PubMed Abstract: Aplyronine A, isolated from the sea hare Aplysia kurodai, possesses an exceedingly potent antitumor effect in vivo and it is one of the promising candidates as an anticancer drug. This macrolide is known to depolymerize F-actin and inhibit the polymerization of actin by forming a 1:1 complex with monomeric actin. The first complex structure of actin-aplyronine A was determined via a synchrotron X-ray analysis at a 1.45 A resolution. As expected, aplyronine A binds to a hydrophobic cleft composed of subdomains 1 and 3 of actin by intercalating its aliphatic tail part into the actin molecule as do the other reported F-actin depolymerizing agents. Unexpectedly, this complex structure shows the specific structural features around the trimethylserine moiety, revealed as an important moiety of aplyronine A for cytotoxicity against HeLa cells. Combining this result and our previous one, the moiety should strongly relate to the specific biological activity of aplyronine A; i.e. a potent antitumor effect.

PubMed: 16406066
DOI: 10.1016/j.jmb.2005.12.031

Experimental method

X-RAY DIFFRACTION (1.45 Å)