6GZ7

Polyamide - DNA complex NMR structure

Summary for 6GZ7

• Entry DOI: 10.2210/pdb6gz7/pdb
• NMR Information: BMRB: 34296
• Descriptor: DNA (5'-D(*CP*GP*AP*TP*GP*TP*AP*CP*AP*TP*CP*G)-3'), dimethyl-[3-[3-[[1-methyl-4-[[1-methyl-4-[[1-methyl-4-[[1-methyl-4-[4-[[1-methyl-4-[[1-methyl-4-[[1-methyl-4-[(1-propan-2-ylimidazol-2-yl)carbonylamino]pyrrol-2-yl]carbonylamino]pyrrol-2-yl]carbonylamino]pyrrol-2-yl]carbonylamino]butanoylamino]imidazol-2-yl]carbonylamino]pyrrol-2-yl]carbonylamino]pyrrol-2-yl]carbonylamino]pyrrol-2-yl]carbonylamino]propanoylamino]propyl]azanium (2 entities in total)
• Functional Keywords: polyamide dna complex, unknown function
• Biological source: synthetic construct
• Total number of polymer chains: 2
• Total formula weight: 9132.59

Authors

Aman, K. (deposition date: 2018-07-03, release date: 2018-11-28, Last modification date: 2024-05-15)

Primary citation

Aman, K.,Padroni, G.,Parkinson, J.A.,Welte, T.,Burley, G.A.
Structural and Kinetic Profiling of Allosteric Modulation of Duplex DNA Induced by DNA-Binding Polyamide Analogues.
Chemistry, 25:2757-2763, 2019

PubMed Abstract: A combined structural and quantitative biophysical profile of the DNA binding affinity, kinetics and sequence-selectivity of hairpin polyamide analogues is described. DNA duplexes containing either target polyamide binding sites or mismatch sequences are immobilized on a microelectrode surface. Quantitation of the DNA binding profile of polyamides containing N-terminal 1-alkylimidazole (Im) units exhibit picomolar binding affinities for their target sequences, whereas 5-alkylthiazole (Nt) units are an order of magnitude lower (low nanomolar). Comparative NMR structural analyses of the polyamide series shows that the steric bulk distal to the DNA-binding face of the hairpin iPr-Nt polyamide plays an influential role in the allosteric modulation of the overall DNA duplex structure. This combined kinetic and structural study provides a foundation to develop next-generation hairpin designs where the DNA-binding profile of polyamides is reconciled with their physicochemical properties.

PubMed: 30407668
DOI: 10.1002/chem.201805338

Experimental method

SOLUTION NMR