BINDING OF AN ANTITUMOR DRUG TO DNA NETROPSIN AND C-G-C-G-A-A-T-T-BRC-G-C-G
BINDING OF AN ANTITUMOR DRUG TO DNA NETROPSIN AND C-G-C-G-A-A-T-T-BRC-G-C-G
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DOI：
10.1016/0022-2836(85)90171-8
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发表时间：
1985-01-01
影响因子：
5.6
通讯作者：
DICKERSON, RE
中科院分区：
文献类型：
--
作者：
KOPKA, ML;YOON, C;DICKERSON, RE
The antitumor antibiotic netropsin was co-crystallized with a double-helical .BETA.-DNA dodecanucleotide of sequence: C-G-C-G-A-A-T-T-BrC-G-C-G, and the structure of the complex was solved by X-ray diffraction at a resolution of 2.2 .ANG.. The structure was 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 2 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.degree., but neither unwinds nor elongates the double helix. The drug molecule is held in place by amide NH H bonds that bridge adenine N-3 and thymine O-2 atoms, exactly as wtih the spine of hydration. The requirement of A .cntdot. T base-pairs in the binding site arises because the N-2 amino group of guanine would demand impermissibly close contacts with netropsin. Substitution of imidazole for pyrrole in netropsin should create a family of lexitropsins capable of reading G .cntdot. C-containing base sequences.
