5XEW

Crystal structure of the [Ni2+-(chromomycin A3)2]-CCG repeats complex

Replaces:  5ERZ

Summary for 5XEW

• Entry DOI: 10.2210/pdb5xew/pdb
• Related: 5ERZ 5ES0
• Descriptor: DNA (5'-D(*TP*TP*CP*CP*GP*CP*CP*GP*CP*CP*GP*AP*A)-3'), 3-C-methyl-4-O-acetyl-alpha-L-Olivopyranose-(1-3)-(2R,5S,6R)-6-methyltetrahydro-2H-pyran-2,5-diol-(1-3)-(2R,5S,6R)-6-methyltetrahydro-2H-pyran-2,5-diol, 2,6-dideoxy-4-O-methyl-alpha-D-galactopyranose-(1-3)-(2R,3R,6R)-6-hydroxy-2-methyltetrahydro-2H-pyran-3-yl acetate, ... (6 entities in total)
• Functional Keywords: trinucleotide repeats, neurological disease, induced fit recognition, metal binding ligand, consecutive bases flip-out, dna deformation, molecular diagnostics, dna-antibiotic complex, dna/antibiotic
• Biological source: synthetic construct
• Total number of polymer chains: 2
• Total formula weight: 10343.74

Authors

Tseng, W.H.,Wu, P.C.,Hou, M.H. (deposition date: 2017-04-06, release date: 2017-06-21, Last modification date: 2024-03-27)

Primary citation

Tseng, W.H.,Chang, C.K.,Wu, P.C.,Hu, N.J.,Lee, G.H.,Tzeng, C.C.,Neidle, S.,Hou, M.H.
Induced-Fit Recognition of CCG Trinucleotide Repeats by a Nickel-Chromomycin Complex Resulting in Large-Scale DNA Deformation
Angew. Chem. Int. Ed. Engl., 56:8761-8765, 2017

PubMed Abstract: Small-molecule compounds targeting trinucleotide repeats in DNA have considerable potential as therapeutic or diagnostic agents against many neurological diseases. Ni (Chro) (Chro=chromomycin A3) binds specifically to the minor groove of (CCG) repeats in duplex DNA, with unique fluorescence features that may serve as a probe for disease detection. Crystallographic studies revealed that the specificity originates from the large-scale spatial rearrangement of the DNA structure, including extrusion of consecutive bases and backbone distortions, with a sharp bending of the duplex accompanied by conformational changes in the Ni chelate itself. The DNA deformation of CCG repeats upon binding forms a GGCC tetranucleotide tract, which is recognized by Ni (Chro) . The extruded cytosine and last guanine nucleotides form water-mediated hydrogen bonds, which aid in ligand recognition. The recognition can be accounted for by the classic induced-fit paradigm.

PubMed: 28544401
DOI: 10.1002/anie.201703989

Experimental method

X-RAY DIFFRACTION (1.751 Å)