6BNA

BINDING OF AN ANTITUMOR DRUG TO DNA. NETROPSIN AND C-G-C-G-A-A-T-T-BRC-G-C-G

Summary for 6BNA

• Entry DOI: 10.2210/pdb6bna/pdb
• Descriptor: DNA (5'-D(*CP*GP*CP*GP*AP*AP*TP*TP*(CBR)P*GP*CP*G)-3'), NETROPSIN (3 entities in total)
• Functional Keywords: b-dna, double helix, complexed with drug, modified, dna
• Total number of polymer chains: 2
• Total formula weight: 7915.04

Authors

Kopka, M.L.,Yoon, C.,Goodsell, D.,Pjura, P.,Dickerson, R.E. (deposition date: 1984-08-30, release date: 1984-10-29, Last modification date: 2024-03-13)

Primary citation

Kopka, M.L.,Yoon, C.,Goodsell, D.,Pjura, P.,Dickerson, R.E.
Binding of an antitumor drug to DNA, Netropsin and C-G-C-G-A-A-T-T-BrC-G-C-G.
J.Mol.Biol., 183:553-563, 1985

PubMed Abstract: 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 A. 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 degrees, 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 X 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 X C-containing base sequences.

PubMed: 2991536
DOI: 10.1016/0022-2836(85)90171-8

Experimental method

X-RAY DIFFRACTION (2.21 Å)