1k9g
From Proteopedia
Crystal Structure of the Complex of Cryptolepine-d(CCTAGG)2
Overview
Cryptolepine, a naturally occurring indoloquinoline alkaloid used as an antimalarial drug in Central and Western Africa, has been found to bind to DNA in a formerly unknown intercalation mode. Evidence from competition dialysis assays demonstrates that cryptolepine is able to bind CG-rich sequences containing nonalternating CC sites. Here we show that cryptolepine interacts with the CC sites of the DNA fragment d(CCTAGG)(2) in a base-stacking intercalation mode. This is the first DNA intercalator complex, from approximately 90 solved by X-ray crystallography, to bind a nonalternating (pyrimidine-pyrimidine) DNA sequence. The asymmetry of the drug induces a perfect stacking with the asymmetric site, allowing for the stability of the complex in the absence of hydrogen bonding interactions. The crystal structure of this antimalarial drug-DNA complex provides evidence for the first nonalternating intercalation and, as such, provides a basis for the design of new anticancer or antimalarial drugs.
About this Structure
Full crystallographic information is available from OCA.
Reference
The antimalarial and cytotoxic drug cryptolepine intercalates into DNA at cytosine-cytosine sites., Lisgarten JN, Coll M, Portugal J, Wright CW, Aymami J, Nat Struct Biol. 2002 Jan;9(1):57-60. PMID:11731803 Page seeded by OCA on Fri May 2 22:28:16 2008
