Novel iron phenanthroline-based photosensitizers for antimicrobial PDT: synthesis, DNA binding and photo-induced DNA cleavage activity

Mechanistic understanding of DNA recombination in the Cre-loxP system has largely been guided by crystallographic structures of tetrameric synaptic complexes. Those studies have suggested a role for protein conformational dynamics that has not been well characterized at the atomic level. We used solution nuclear magnetic resonance (NMR) spectroscopy to discover the link between intrinsic flexibility and function in Cre recombinase. Transverse relaxation-optimized spectroscopy (TROSY) NMR spectra show the N-terminal and C-terminal catalytic domains (CreNTD and CreCat) to be structurally independent. Amide 15N relaxation measurements of the CreCat domain reveal fast-timescale dynamics in most regions that exhibit conformational differences in active and inactive Cre protomers in crystallographic tetramers. However, the C-terminal helix αN, implicated in assembly of synaptic complexes and regulation of DNA cleavage activity via trans protein–protein interactions, is unexpectedly rigid in free Cre. Chemical shift perturbations and intra- and intermolecular paramagnetic relaxation enhancement (PRE) NMR data reveal an alternative autoinhibitory conformation for the αN region of free Cre, wherein it packs in cis over the protein DNA binding surface and active site. Moreover, binding to loxP DNA induces a conformational change that dislodges the C terminus, resulting in a cis-to-trans switch that is likely to enable protein–protein interactions required for assembly of recombinogenic Cre intasomes. These findings necessitate a reexamination of the mechanisms by which this widely utilized gene-editing tool selects target sites, avoids spurious DNA cleavage activity, and controls DNA recombination efficiency.

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Synthesis, crystal structure, Hirshfeld surface analysis, DNA binding, DNA cleavage activity and molecular docking of a new Schiff base nickel(II) complex

Journal of Biomolecular Structure and Dynamics ◽

10.1080/07391102.2020.1784789 ◽

2020 ◽

pp. 1-11

Author(s):

Jianfang Dong ◽

Lei Gao ◽

Bo Zhang ◽

Tao Xu ◽

Lei Wang ◽

...

Keyword(s):

Crystal Structure ◽

Schiff Base ◽

Molecular Docking ◽

Dna Binding ◽

Surface Analysis ◽

Dna Cleavage ◽

Hirshfeld Surface ◽

Hirshfeld Surface Analysis ◽

Cleavage Activity ◽

Dna Cleavage Activity

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Synthesis, structure, DNA binding and DNA cleavage activity of oxovanadium(IV) N-salicylidene-S-methyldithiocarbazate complexes of phenanthroline bases

Journal of Inorganic Biochemistry ◽

10.1016/j.jinorgbio.2007.12.031 ◽

2008 ◽

Vol 102 (7) ◽

pp. 1463-1472 ◽

Cited By ~ 91

Author(s):

Pijus K. Sasmal ◽

Ashis K. Patra ◽

Akhil R. Chakravarty

Keyword(s):

Dna Binding ◽

Dna Cleavage ◽

Cleavage Activity ◽

Dna Cleavage Activity ◽

Phenanthroline Bases

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Synthesis and Characterisation of RuII Polypyridyl Complexes: DNA-Binding, Photocleavage, and Topoisomerase I and II Inhibitory Activity

Australian Journal of Chemistry ◽

10.1071/ch13329 ◽

2013 ◽

Vol 66 (11) ◽

pp. 1406 ◽

Cited By ~ 3

Author(s):

Xiaojun He ◽

Guang Yang ◽

Xiaonan Sun ◽

Lingjun Xie ◽

Lifeng Tan

Keyword(s):

Dna Binding ◽

Dna Cleavage ◽

Topoisomerase I ◽

Mixed Ligand ◽

Dual Inhibitor ◽

Cleavage Activity ◽

Dna Cleavage Activity ◽

Pbr322 Dna ◽

Dna Strand ◽

Strand Passage

Two mixed-ligand ruthenium(ii) complexes [Ru(phen)2(cptcp)]2+ (Ru1; phen = 1,10-phenanthroline, cptcp = 2-(4-carbazol-9-yl-phenyl)-1H-1,3,7,8-tetraaza-cyclopenta-[l]-phenanthrene) and [Ru(phen)2(btcpc)]2+ (Ru2; btcpc = 9-butyl-6-(1H-1,3,7,8-tetraaza-cyclo-cyclopenta-[l]-phenanthren-2-yl)-9H-carbazole-3-carbaldehyde) have been synthesised and characterised. The DNA-binding behaviours of the two complexes have been investigated by using spectroscopic and viscosity measurements. Results suggest that the two complexes bind to DNA by intercalation. The photocleavage of plasmid pBR322 DNA indicates that Ru1 exhibits more effective DNA cleavage activity in comparison to that exhibited by Ru2 under the same conditions, and different cleavage mechanisms are determined. Topoisomerase inhibition and DNA strand passage assay confirm that Ru1 may act as an efficient dual inhibitor of topoisomerases I and II, whereas Ru2 may only act as a single inhibitor of topoisomerases II.

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