6AST

NMR and Restrained Molecular Dynamics Determination of the Structure of an Aza-Benzimidazole Derivative Complex with the DNA Minor Groove of an -AAGATA Sequence

Summary for 6AST

• Entry DOI: 10.2210/pdb6ast/pdb
• NMR Information: BMRB: 30336
• Descriptor: DNA (5'-D(*CP*CP*AP*AP*GP*AP*TP*AP*G)-3'), DNA (5'-D(*CP*TP*AP*TP*CP*TP*TP*GP*G)-3'), amino(4-{[(2-{4-[amino(iminio)methyl]phenyl}-3H-imidazo[4,5-b]pyridin-5-yl)oxy]methyl}phenyl)methaniminium (3 entities in total)
• Functional Keywords: small molecule, minor groove binder, mixed base pair recogniition, heterocyclic diamidine, dna
• Biological source: synthetic construct; More
• Total number of polymer chains: 2
• Total formula weight: 5858.07

Authors

Harika, N.K.,Germann, M.W.,Wilson, W.D. (deposition date: 2017-08-25, release date: 2018-01-31, Last modification date: 2024-05-01)

Primary citation

Harika, N.K.,Germann, M.W.,Wilson, W.D.
First Structure of a Designed Minor Groove Binding Heterocyclic Cation that Specifically Recognizes Mixed DNA Base Pair Sequences.
Chemistry, 23:17612-17620, 2017

PubMed Abstract: The high-resolution NMR structure of the first heterocyclic, non-amide, organic cation that strongly and selectively recognizes mixed AT/GC bp (bp=base pair) sequences of DNA in a 1:1 complex is described. Compound designs of this type provide essential methods for control of functional, non-genomic DNA sequences and have broad cell uptake capability, based on studies from animals to humans. The high-resolution structural studies described in this report are essential for understanding the molecular basis for the sequence-specific binding as well as for new ideas for additional compound designs for sequence-specific recognition. The molecular features, in this report, explain the mechanism of recognition of both A⋅T and G⋅C bps and are an interesting molecular recognition story. Examination of the experimental structure and the NMR restrained molecular dynamics model suggests that recognition of the G⋅C base pair involves two specific H-bonds. The structure illustrates a wealth of information on different DNA interactions and illustrates an interfacial water molecule that is a key component of the complex.

PubMed: 29044822
DOI: 10.1002/chem.201704563

Experimental method

SOLUTION NMR