6I4N

Dodecamer DNA containing the synthetic base pair P-Z in complex with a pyrrole-imidazole polyamide

Summary for 6I4N

• Entry DOI: 10.2210/pdb6i4n/pdb
• Descriptor: DNA (5'-D(*CP*GP*AP*TP*(DP)P*TP*AP*(DZ)P*AP*TP*CP*G)-3'), 3-[3-[[4-[[4-[[4-[[4-[[(2~{R})-2-azaniumyl-4-[[1-methyl-4-[[1-methyl-4-[[1-methyl-4-[(1-methylimidazol-2-yl)carbonylamino]pyrrol-2-yl]carbonylamino]pyrrol-2-yl]carbonylamino]pyrrol-2-yl]carbonylamino]butanoyl]amino]-1-methyl-imidazol-2-yl]carbonylamino]-1-methyl-pyrrol-2-yl]carbonylamino]-1-methyl-pyrrol-2-yl]carbonylamino]-1-methyl-pyrrol-2-yl]carbonylamino]propanoylamino]propyl-dimethyl-azanium (2 entities in total)
• Functional Keywords: dna, synthetic base pair, z, p, pyrrole-imidazole polyamide
• Biological source: synthetic construct
• Total number of polymer chains: 2
• Total formula weight: 8652.18

Authors

Padroni, G.,Parkison, J.,Burley, G.A. (deposition date: 2018-11-10, release date: 2019-06-12, Last modification date: 2024-05-15)

Primary citation

Padroni, G.,Withers, J.M.,Taladriz-Sender, A.,Reichenbach, L.F.,Parkinson, J.A.,Burley, G.A.
Sequence-Selective Minor Groove Recognition of a DNA Duplex Containing Synthetic Genetic Components.
J.Am.Chem.Soc., 141:9555-9563, 2019

PubMed Abstract: The structural basis of minor groove recognition of a DNA duplex containing synthetic genetic information by hairpin pyrrole-imidazole polyamides is described. Hairpin polyamides induce a higher melting stabilization of a DNA duplex containing the unnatural P·Z base-pair when an imidazole unit is aligned with a P nucleotide. An NMR structural study showed that the incorporation of two isolated P·Z pairs enlarges the minor groove and slightly narrows the major groove at the site of this synthetic genetic information, relative to a DNA duplex consisting entirely of Watson-Crick base-pairs. Pyrrole-imidazole polyamides bind to a P·Z-containing DNA duplex to form a stable complex, effectively mimicking a G·C pair. A structural hallmark of minor groove recognition of a P·Z pair by a polyamide is the reduced level of allosteric distortion induced by binding of a polyamide to a DNA duplex. Understanding the molecular determinants that influence minor groove recognition of DNA containing synthetic genetic components provides the basis to further develop unnatural base-pairs for synthetic biology applications.

PubMed: 31117639
DOI: 10.1021/jacs.8b12444

Experimental method

SOLUTION NMR