The α-thio and/or β-γ-hypophosphate analogs of ATP as cofactors of T4 DNA ligase

Pawłowska, Róża; Korczyński, Dariusz; Nawrot, Barbara; Stec, Wojciech J.; Chworoś, Arkadiusz

doi:10.1016/j.bioorg.2016.06.003

Cited by 9 publications

(10 citation statements)

References 25 publications

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“…On the other hand, nucleoside analogues and hypodiphosphoric acid itself can behave as substrates in phosphorylation reactions (Setondji et al, 1971;Kukhanova et al, 2005). Additionally, nucleoside hypodiphosphates may play a cofactor role in DNA ligase activities (Pawlowska et al, 2016).…”

Section: Introductionmentioning

confidence: 99%

Adenosine hypodiphosphate ester, an analogue of ADP: analysis of the adenine–hypodiphosphate interaction mode in hypodiphosphate nucleotides and adenine salts

et al. 2018

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Adenosine diphosphate (ADP) plays a crucial role in cell biochemistry, especially in metabolic pathways and energy storage. ADP itself, as well as many of its analogues, such as adenosine hypodiphosphate (AhDP), has been studied extensively, in particular in terms of enzymatic activity. However, structural studies in the solid state, especially for AhDP, are still missing. An analogue of ADP, i.e. adenosine hypodiphosphate ester, has been synthesized and characterized in the crystalline form as two hydrated sodium salts of 2':3'-isopropylideneadenosine 5'-hypodiphosphate (HAhDP, CHNOP for the neutral form), namely pentasodium tetrakis(2':3'-isopropylideneadenosine 5'-hypodiphosphate) tetracosahydrate, 5Na·3CHNOP·CHNOP·24HO or Na(HAhDP)(HAhDP)·24HO, (I), and sodium tetrakis(2':3'-isopropylideneadenosine 5'-hypodiphosphate) pentadecahydrate, Na·CHNOP·2CHNOP·CHNOP·15HO or Na(HAhDP)(HAhDP)(HAhDP)·15HO, (II). Crystal structure analyses of (I) and (II) reveal two nucleoside hypodiphosphate ions in the asymmetric units with different ionization states of the hypodiphosphate unit and adenine base. For all AhDP nucleotides, the same anti conformation about the N-glycosidic bond and similar puckering of the ribose ring have been found. AhDP geometry and interactions have been compared to ADP nucleotides deposited in the Cambridge Structural Database. The adenine-hypodiphosphate interactions, identified as defining nucleotide self-assembly, have been analysed in model systems, i.e. the adenine (Ade) salts of hypodiphosphoric acid, namely bis(adeninium) hypodiphosphate dihydrate, 2CHN·HPO·2HO or (AdeH)(HPO)·2HO, (III), and bis(adeninium) hypodiphosphate, 2CHN·HPO or (AdeH)(HPO), (IV).

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Section: Introductionmentioning

confidence: 99%

Adenosine hypodiphosphate ester, an analogue of ADP: analysis of the adenine–hypodiphosphate interaction mode in hypodiphosphate nucleotides and adenine salts

et al. 2018

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“…Since TNAP is involved in the degradation of extracellular nucleotides via the hydrolysis of pyrophosphate, it may be assumed that this protein also participates in the degradation of nucleotide analogues. Among this class of compounds, especially interesting are β,γ-modified nucleotides, such as bisphosphonates [39,40], hypophosphates [41] and ATP derivatives, which may be hydrolyzed by ectonucleotidases with the release of modified pyrophosphate analogues. TNAP is considered as a potential target for anti-calcification drug design [4].…”

Section: Discussionmentioning

confidence: 99%

Tissue-Nonspecific Alkaline Phosphatase (TNAP) as the Enzyme Involved in the Degradation of Nucleotide Analogues in the Ligand Docking and Molecular Dynamics Approaches

et al. 2021

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Tissue-nonspecific alkaline phosphatase (TNAP) is known to be involved in the degradation of extracellular ATP via the hydrolysis of pyrophosphate (PPi). We investigated, using three different computational methods, namely molecular docking, thermodynamic integration (TI) and conventional molecular dynamics (MD), whether TNAP may also be involved in the utilization of β,γ-modified ATP analogues. For that, we analyzed the interaction of bisphosphonates with this enzyme and evaluated the obtained structures using in silico studies. Complexes formed between pyrophosphate, hypophosphate, imidodiphosphate, methylenediphosphonic acid monothiopyrophosphate, alendronate, pamidronate and zoledronate with TNAP were generated and analyzed based on ligand docking, molecular dynamics and thermodynamic integration. The obtained results indicate that all selected ligands show high affinity toward this enzyme. The forming complexes are stabilized through hydrogen bonds, electrostatic interactions and van der Waals forces. Short- and middle-term molecular dynamics simulations yielded very similar affinity results and confirmed the stability of the protein and its complexes. The results suggest that certain effectors may have a significant impact on the enzyme, changing its properties.

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“…In the case of DNA ligases, modified co-factors have produced a range of effects and it is not straightforward to predict their effects, as we discuss below. Furthermore, an influence on the enzyme activity does not necessarily require major alterations to the chemical groups of the co-factor, as demonstrated recently for T4 DNA ligase exhibiting stereo-selective properties towards modified ATP compounds [ 88 ].…”

Section: Inhibitors and Non-natural Substrates Of Dna Ligasesmentioning

confidence: 99%

Biochemical and structural characterization of DNA ligases from bacteria and archaea

2016

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The α-thio and/or β-γ-hypophosphate analogs of ATP as cofactors of T4 DNA ligase

Cited by 9 publications

References 25 publications

Adenosine hypodiphosphate ester, an analogue of ADP: analysis of the adenine–hypodiphosphate interaction mode in hypodiphosphate nucleotides and adenine salts

Adenosine hypodiphosphate ester, an analogue of ADP: analysis of the adenine–hypodiphosphate interaction mode in hypodiphosphate nucleotides and adenine salts

Tissue-Nonspecific Alkaline Phosphatase (TNAP) as the Enzyme Involved in the Degradation of Nucleotide Analogues in the Ligand Docking and Molecular Dynamics Approaches

Biochemical and structural characterization of DNA ligases from bacteria and archaea

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