1K9G

Crystal Structure of the Complex of Cryptolepine-d(CCTAGG)2

Summary for 1K9G

• Entry DOI: 10.2210/pdb1k9g/pdb
• Descriptor: 5'-D(*CP*CP*TP*AP*GP*G)-3', 5-METHYL-5H-INDOLO[3,2-B]QUINOLINE (3 entities in total)
• Functional Keywords: dna intercalator complex, dna
• Total number of polymer chains: 1
• Total formula weight: 2273.78

Authors

Lisgarten, J.N.,Coll, M.,Portugal, J.,Wright, C.W.,Aymami, J. (deposition date: 2001-10-29, release date: 2001-11-30, Last modification date: 2024-02-07)

Primary citation

Lisgarten, J.N.,Coll, M.,Portugal, J.,Wright, C.W.,Aymami, J.
The antimalarial and cytotoxic drug cryptolepine intercalates into DNA at cytosine-cytosine sites.
Nat.Struct.Biol., 9:57-60, 2002

PubMed Abstract: 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.

PubMed: 11731803
DOI: 10.1038/nsb729

Experimental method

X-RAY DIFFRACTION (1.4 Å)