Structure of bistramide A-actin complex at a 1.35 angstroms resolution

J Am Chem Soc. 2006 Mar 29;128(12):3882-3. doi: 10.1021/ja058319c.


Bistramide A is a highly potent antiproliferative marine natural product from Lissoclinum bistratum. We have previously established actin as the primary cellular receptor of bistramide A. We report herein the X-ray structure of bistramide A bound to monomeric actin at a resolution of 1.35 A. The most notable aspect of the bistramide A-actin structure is an extensive hydrogen-bonding network established upon a deep penetration of the central segment of bistramide A into the actin-binding cleft between subdomains 1 and 3. The structure presents the first insight into the observed ability of bistramide A to modulate G-actin polymerization. The structural information combined with our ability to chemically modify the bistramide framework provides the basis for rational development of a series of new synthetic analogues as useful probes for studying actin cytoskeleton and as potential therapeutic leads.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Acetamides / chemistry*
  • Acetamides / metabolism
  • Actins / chemistry*
  • Actins / metabolism
  • Hydrogen Bonding
  • Hydrophobic and Hydrophilic Interactions
  • Kinetics
  • Models, Molecular
  • Protein Conformation
  • Protein Structure, Tertiary
  • Pyrans / chemistry*
  • Pyrans / metabolism
  • Spiro Compounds / chemistry
  • Spiro Compounds / metabolism


  • Acetamides
  • Actins
  • Pyrans
  • Spiro Compounds
  • bistratene A