Binding of an antitumor drug to DNA. Netropsin and C-G-C-G-A-A-T-T-BrC-G-C-G

Mary L. Kopka, Chun Yoon, David Goodsell, Philip Pjura, Richard E. Dickerson

Research output: Contribution to journalArticlepeer-review

411 Scopus citations


The antitumor antibiotic netropsin has been co-crystallized with a double-helical B-DNA dodecanucleotide of sequence: C-G-C-G-A-A-T-T-BrC-G-C-G, and the structure of the complex has been solved by X-ray diffraction at a resolution of 2.2 Å. The structure has been refined independently by Jack-Levitt and Hendrickson-Konnert least-squares methods, leading to a final residual error of 0.257 by the Jack-Levitt approach (0.211 for two-sigma data) or 0.248 by the Hendrickson-Konnert approach, with no significant difference between refined structures. The netropsin molecule displaces the spine of hydration and fits snugly within the minor groove in the A-A-T-T center. It widens the groove slightly and bends the helix axis back by 8 °, but neither unwinds nor elongates the double helix. The drug molecule is held in place by amide NH hydrogen bonds that bridge adenine N-3 and thymine O-2 atoms, exactly as with the spine of hydration. The requirement of A · T base-pairs in the binding site arises because the N-2 amino group of guanine would demand impermissibly close contacts with netropsin. It is proposed that substitution of imidazole for pyrrole in netropsin should create a family of "lexitropsins" capable of reading G · C-containing base sequences.

Original languageEnglish (US)
Pages (from-to)553-563
Number of pages11
JournalJournal of molecular biology
Issue number4
StatePublished - Jun 25 1985
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Structural Biology
  • Molecular Biology


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