Structure of bistramide A-actin complex at a 1.35 angstroms resolution.
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.
Department of Chemistry, University of Chicago, Chicago, Illinois 60637, USA.
Syed Alipayam
SA
Rizvi
Valentina
V
Tereshko
Anthony A
AA
Kossiakoff
Sergey A
SA
Kozmin
D000081:Acetamides / Q000737:chemistry* / Q000378:metabolism; D000199:Actins / Q000737:chemistry* / Q000378:metabolism; D006860:Hydrogen Bonding; D057927:Hydrophobic and Hydrophilic Interactions; D007700:Kinetics; D008958:Models, Molecular; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D011714:Pyrans / Q000737:chemistry* / Q000378:metabolism; D013141:Spiro Compounds / Q000737:chemistry / Q000378:metabolism
D000081:Acetamides; D000199:Actins; D011714:Pyrans; D013141:Spiro Compounds; C059975:bistratene A