7YVW

NMR determination of the 2:1 binding motif structure involving cytosine flipping out for the recognition of the CGG/CGG triad DNA

Summary for 7YVW

• Entry DOI: 10.2210/pdb7yvw/pdb
• Descriptor: DNA (5'-D(*CP*TP*AP*AP*CP*GP*GP*AP*AP*TP*G)-3'), DNA (5'-D(*CP*AP*TP*TP*CP*GP*GP*TP*TP*AP*G)-3'), 3-[3-[(7-methyl-1,8-naphthyridin-2-yl)carbamoyloxy]propylamino]propyl ~{N}-(7-methyl-1,8-naphthyridin-2-yl)carbamate (3 entities in total)
• Functional Keywords: gg mismatch, drug, complex, dna
• Biological source: synthetic construct; More
• Total number of polymer chains: 2
• Total formula weight: 7753.55

Authors

Furuita, K.,Yamada, T.,Sakurabayashi, S.,Nomura, M.,Kojima, C.,Nakatani, K. (deposition date: 2022-08-19, release date: 2023-06-14, Last modification date: 2024-05-15)

Primary citation

Yamada, T.,Furuita, K.,Sakurabayashi, S.,Nomura, M.,Kojima, C.,Nakatani, K.
NMR determination of the 2:1 binding complex of naphthyridine carbamate dimer (NCD) and CGG/CGG triad in double-stranded DNA.
Nucleic Acids Res., 50:9621-9631, 2022

PubMed Abstract: Trinucleotide repeat (TNR) diseases are caused by the aberrant expansion of CXG (X = C, A, G and T) sequences in genomes. We have reported two small molecules binding to TNR, NCD, and NA, which strongly bind to CGG repeat (responsible sequence of fragile X syndrome) and CAG repeat (Huntington's disease). The NMR structure of NA binding to the CAG/CAG triad has been clarified, but the structure of NCD bound to the CGG/CGG triad remained to be addressed. We here report the structural determination of the NCD-CGG/CGG complex by NMR spectroscopy and the comparison with the NA-CAG/CAG complex. While the NCD-CGG/CGG structure shares the binding characteristics with that of the NA-CAG/CAG complex, a significant difference was found in the overall structure caused by the structural fluctuation at the ligand-bound site. The NCD-CGG/CGG complex was suggested in the equilibrium between stacked and kinked structures, although NA-CAG/CAG complex has only the stacked structures. The dynamic fluctuation of the NCD-CGG/CGG structure at the NCD-binding site suggested room for optimization in the linker structure of NCD to gain improved affinity to the CGG/CGG triad.

PubMed: 36095126
DOI: 10.1093/nar/gkac740

Experimental method

SOLUTION NMR