Atomic-resolution STM structure of DNA and localization of the retinoic acid binding site.
Single-molecule imaging by scanning tunnelling microscopy (STM) yields the atomic-resolution (0.6A) structure of individual B-type DNA molecules. The strong correlation between these STM structures and those predicted from the known base sequence indicates that sequencing of single DNA molecules using STM may be feasible. There is excellent agreement between the STM and X-ray structures, but subtle differences exist due to radial distortions. We show that the interactions of other molecules with DNA, their binding configurations, and the structure of these complexes can be studied at the single-molecule level. The anti-cancer drug retinoic acid (RA) binds selectively to the minor groove of DNA with up to 6 RA molecules per DNA turn and with the plane of the RA molecule approximately parallel to the DNA symmetry axis. Similar studies for other drug molecules will be valuable in the a priori evaluation of the effectiveness of anti-cancer drugs.
Zareie
M Hadi
MH
School of Physics A28, University of Sydney, NSW 2006, Australia.
Lukins
Philip B
PB
D000970:Antineoplastic Agents / Q000494:pharmacology; D001665:Binding Sites; D004247:DNA / Q000032:analysis* / Q000378:metabolism; D016252:Microscopy, Scanning Tunneling / Q000379:methods*; D008958:Models, Molecular; D009690:Nucleic Acid Conformation; D011485:Protein Binding; D014212:Tretinoin / Q000737:chemistry* / Q000378:metabolism*; D014867:Water / Q000378:metabolism
D000970:Antineoplastic Agents; D014867:Water; D014212:Tretinoin; D004247:DNA