3OMJ

Structural Basis for Cyclic Py-Im Polyamide Allosteric Inhibition of Nuclear Receptor Binding

3OMJ の概要

• エントリーDOI: 10.2210/pdb3omj/pdb
• 分子名称: 5'-D(*CP*(C38)P*AP*GP*TP*AP*CP*TP*GP*G)-3', CALCIUM ION, (23R,52R)-23,52-diamino-5,11,17,28,34,40,46,57-octamethyl-2,5,8,11,14,17,20,25,28,31,34,37,40,43,46,49,54,57,60,64-icosaazanonacyclo[54.2.1.1~4,7~.1~10,13~.1~16,19~.1~27,30~.1~33,36~.1~39,42~.1~45,48~]hexahexaconta-1(58),4(66),6,10(65),12,16(64),18,27(63),29,33(62),35,39(61),41,45(60),47,56(59)-hexadecaene-3,9,15,21,26,32,38,44,50,55-decone, ... (4 entities in total)
• 機能のキーワード: cyclic py-im polyamide, dna
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 7681.33

構造登録者

Chenoweth, D.M. (登録日: 2010-08-27, 公開日: 2010-09-08, 最終更新日: 2024-02-21)

主引用文献

Chenoweth, D.M.,Dervan, P.B.
Structural basis for cyclic py-im polyamide allosteric inhibition of nuclear receptor binding.
J.Am.Chem.Soc., 132:14521-14529, 2010

PubMed Abstract: Pyrrole-imidazole polyamides are a class of small molecules that can be programmed to bind a broad repertoire of DNA sequences, disrupt transcription factor-DNA interfaces, and modulate gene expression pathways in cell culture experiments. In this paper we describe a high-resolution X-ray crystal structure of a β-amino turn-linked eight-ring cyclic Py-Im polyamide bound to the central six base pairs of the sequence d(5'-CCAGTACTGG-3')(2), revealing significant modulation of DNA shape. We compare the DNA structural perturbations induced by DNA-binding transcripton factors, androgen receptor and glucocorticoid receptor, in the major groove to those induced by cyclic polyamide binding in the minor groove. The cyclic polyamide is an allosteric modulator that perturbs the DNA structure in such a way that nuclear receptor protein binding is no longer compatible. This allosteric perturbation of the DNA helix provides a molecular basis for disruption of transcription factor-DNA interfaces by small molecules, a minimum step in chemical control of gene networks.

PubMed: 20812704
DOI: 10.1021/ja105068b

実験手法

X-RAY DIFFRACTION (0.95 Å)