UNUSUAL ACTD/DNA_TA COMPLEX STRUCTUREUNUSUAL ACTD/DNA_TA COMPLEX STRUCTURE

Structural highlights

1l1v is a 2 chain structure with sequence from Streptomyces antibioticus. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:Solution NMR
Ligands:, , ,
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Publication Abstract from PubMed

Many anticancer drugs interact directly with DNA to exert their biological functions. To date, all noncovalent, intercalating drugs interact with DNA exclusively by inserting their chromophores into base steps to form elongated and unwound duplex structures without disrupting the flanking base pairs. By using actinomycin D (ActD)-5'-GXC/CYG-5' complexes as examples, we have found a rather unusual interaction mode for the intercalated drug; the central Watson-Crick X/Y base pairs are looped out and displaced by the ActD chromophore. The looped-out bases are not disordered but interact perpendicularly with the base/chromophore and form specific H bonds with DNA. Such a complex structure provides intriguing insights into how ligand interacts with DNA and enlarges the repertoires for sequence-specific DNA recognition.

Looped out and perpendicular: deformation of Watson-Crick base pair associated with actinomycin D binding.,Chou SH, Chin KH, Chen FM Proc Natl Acad Sci U S A. 2002 May 14;99(10):6625-30. PMID:12011426[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

  1. Chou SH, Chin KH, Chen FM. Looped out and perpendicular: deformation of Watson-Crick base pair associated with actinomycin D binding. Proc Natl Acad Sci U S A. 2002 May 14;99(10):6625-30. PMID:12011426 doi:10.1073/pnas.102580399
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