3I5L

Allosteric Modulation of DNA by Small Molecules

Summary for 3I5L

• Entry DOI: 10.2210/pdb3i5l/pdb
• Related: 3I5E
• Descriptor: 5'-D(*CP*CP*AP*GP*GP*(C38)P*CP*TP*GP*G)-3', CALCIUM ION, (22R,51R)-22,51-diamino-5,11,17,28,34,40,46,57-octamethyl-2,5,8,11,14,17,20,25,28,31,34,37,40,43,46,49,54,57,60,61,64,6 5-docosaazanonacyclo[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)
• Functional Keywords: cyclic polyamide, dna binder, minor groove binder, pyim polyamide, dna
• Total number of polymer chains: 2
• Total formula weight: 7725.36

Authors

Chenoweth, D.M.,Dervan, P.B. (deposition date: 2009-07-05, release date: 2009-07-28, Last modification date: 2024-02-21)

Primary citation

Chenoweth, D.M.,Dervan, P.B.
Allosteric modulation of DNA by small molecules
Proc.Natl.Acad.Sci.USA, 106:13175-13179, 2009

PubMed Abstract: Many human diseases are caused by dysregulated gene expression. The oversupply of transcription factors may be required for the growth and metastatic behavior of human cancers. Cell permeable small molecules that can be programmed to disrupt transcription factor-DNA interfaces could silence aberrant gene expression pathways. Pyrrole-imidazole polyamides are DNA minor-groove binding molecules that are programmable for a large repertoire of DNA motifs. A high resolution X-ray crystal structure of an 8-ring cyclic Py/Im polyamide bound to the central 6 bp of the sequence d(5'-CCAGGCCTGG-3')2 reveals a 4 A widening of the minor groove and compression of the major groove along with a >18 degrees bend in the helix axis toward the major groove. 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: 19666554
DOI: 10.1073/pnas.0906532106

Experimental method

X-RAY DIFFRACTION (1.18 Å)