Inhibition of DNA Binding by Human Estrogen-Related Receptor 2 and Estrogen Receptor α with Minor Groove Binding Polyamides†

Biochemistry ◽  
2005 ◽  
Vol 44 (11) ◽  
pp. 4196-4203 ◽  
Author(s):  
Micah D. Gearhart ◽  
Liliane Dickinson ◽  
Jennifer Ehley ◽  
Christian Melander ◽  
Peter B. Dervan ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
Dna Binding ◽  
Minor Groove ◽  
Estrogen Receptor Α ◽  
Minor Groove Binding ◽  
Groove Binding ◽  
Estrogen Related Receptor

scholarly journals Genetic Analysis of Phage Mu Mor Protein Amino Acids Involved in DNA Minor Groove Binding and Conformational Changes

2011 ◽  
Vol 286 (41) ◽  
pp. 35852-35862 ◽  
Author(s):  
Muthiah Kumaraswami ◽  
Lakshmi Avanigadda ◽  
Rajendra Rai ◽  
Hee-Won Park ◽  
Martha M. Howe
Keyword(s):  
Dna Binding ◽  
Rna Polymerase ◽  
Binding Site ◽  
Conformational Changes ◽  
Minor Groove ◽  
Minor Groove Binding ◽  
Groove Binding ◽  
Specific Chemical ◽  
Mutant Proteins ◽  
Dna Minor Groove

Gene expression during lytic development of bacteriophage Mu occurs in three phases: early, middle, and late. Transcription from the middle promoter, Pm, requires the phage-encoded activator protein Mor and the bacterial RNA polymerase. The middle promoter has a −10 hexamer, but no −35 hexamer. Instead Pm has a hyphenated inverted repeat that serves as the Mor binding site overlapping the position of the missing −35 element. Mor binds to this site as a dimer and activates transcription by recruiting RNA polymerase. The crystal structure of the His-Mor dimer revealed three structural elements: an N-terminal dimerization domain, a C-terminal helix-turn-helix DNA-binding domain, and a β-strand linker between the two domains. We predicted that the highly conserved residues in and flanking the β-strand would be essential for the conformational flexibility and DNA minor groove binding by Mor. To test this hypothesis, we carried out single codon-specific mutagenesis with degenerate oligonucleotides. The amino acid substitutions were identified by DNA sequencing. The mutant proteins were characterized for their overexpression, solubility, DNA binding, and transcription activation. This analysis revealed that the Gly-Gly motif formed by Gly-65 and Gly-66 and the β-strand side chain of Tyr-70 are crucial for DNA binding by His-tagged Mor. Mutant proteins with substitutions at Gly-74 retained partial activity. Treatment with the minor groove- and GC-specific chemical chromomycin A3 demonstrated that chromomycin prevented His-Mor binding but could not disrupt a pre-formed His-Mor·DNA complex, consistent with the prediction that Mor interacts with the minor groove of the GC-rich spacer in the Mor binding site.

scholarly journals 1H NMR study of [d(GCGATCGC)]2 and its interaction with minor groove binding 4',6-diamidino-2-phenylindole.

1993 ◽  
Vol 268 (6) ◽  
pp. 3944-3951
Author(s):  
E. Trotta ◽  
E. D'Ambrosio ◽  
N. Del Grosso ◽  
G. Ravagnan ◽  
M. Cirilli ◽  
...  
Keyword(s):  
1H Nmr ◽  
Minor Groove ◽  
Minor Groove Binding ◽  
Groove Binding ◽  
Nmr Study

scholarly journals Interaction between DNA, Albumin and Apo-Transferrin and Iridium(III) Complexes with Phosphines Derived from Fluoroquinolones as a Potent Anticancer Drug

2021 ◽  
Vol 14 (7) ◽  
pp. 685
Author(s):  
Sandra Amanda Kozieł ◽  
Monika Katarzyna Lesiów ◽  
Daria Wojtala ◽  
Edyta Dyguda-Kazimierowicz ◽  
Dariusz Bieńko ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Serum Proteins ◽  
Docking Study ◽  
Minor Groove ◽  
Docking Studies ◽  
Minor Groove Binding ◽  
Binding Modes ◽  
Groove Binding ◽  
Molecular Docking Study ◽  
Threading Intercalation

A group of cytotoxic half-sandwich iridium(III) complexes with aminomethyl(diphenyl)phosphine derived from fluoroquinolone antibiotics exhibit the ability to (i) accumulate in the nucleus, (ii) induce apoptosis, (iii) activate caspase-3/7 activity, (iv) induce the changes in cell cycle leading to G2/M phase arrest, and (v) radicals generation. Herein, to elucidate the cytotoxic effects, we investigated the interaction of these complexes with DNA and serum proteins by gel electrophoresis, fluorescence spectroscopy, circular dichroism, and molecular docking studies. DNA binding experiments established that the complexes interact with DNA by moderate intercalation and predominance of minor groove binding without the capability to cause a double-strand cleavage. The molecular docking study confirmed two binding modes: minor groove binding and threading intercalation with the fluoroquinolone part of the molecule involved in pi stacking interactions and the Ir(III)-containing region positioned within the major or minor groove. Fluorescence spectroscopic data (HSA and apo-Tf titration), together with molecular docking, provided evidence that Ir(III) complexes can bind to the proteins in order to be transferred. All the compounds considered herein were found to bind to the tryptophan residues of HSA within site I (subdomain II A). Furthermore, Ir(III) complexes were found to dock within the apo-Tf binding site, including nearby tyrosine residues.

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