Phosphodeoxyribosyltransferases, Designed Enzymes for Deoxyribonucleotides Synthesis

Kaminski, P.A.; Labesse, Gilles

doi:10.1074/jbc.m112.446492

Cited by 14 publications

(8 citation statements)

References 48 publications

(44 reference statements)

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“…Mechanistically, the hydrolysis of substrates in both enzymes proceeds through the formation of an α-deoxyribose-5-phosphate-enzyme covalent intermediate via a conserved glutamate residue. The new variants are able to transfer α-deoxyribose 5-phosphate, α-deoxyribose 5-triphosphate or α-deoxyribose 5-O-(1-thiotriphosphate) between cytosine or adenine, and modified nucleobases like 5-fluorouracil, 5-bromouracil, 2,6-diaminopurine, 6-chloropurine, and 2,6-dichloropurine (Kaminski and Labesse, 2013) with varying degree of efficacy (Scheme 24).…”

Section: Monophosphatesmentioning

confidence: 98%

“…A new chimeric enzyme with phosphodeoxyribosyltransferase activity was built through a structure-based design by Kaminski and Labesse (2013) using two distantly related enzymes: nucleoside deoxyribosyltransferase (EC 2.4.2.6) from Lactobacilli and deoxyribonucleoside 5′-nucleotide nucleosidase (EC 3.2.2.-) from rat. The concept was based on several structural similarities shared by both enzymes, such as the adoption of a Rossmann fold and a common catalytic triad.…”

Section: Monophosphatesmentioning

confidence: 99%

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Biocatalytic approaches applied to the synthesis of nucleoside prodrugs

Iglesias

Lewkowicz

Médici

et al. 2015

Biotechnology Advances

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Section: Monophosphatesmentioning

confidence: 98%

Section: Monophosphatesmentioning

confidence: 99%

Biocatalytic approaches applied to the synthesis of nucleoside prodrugs

Iglesias

Lewkowicz

Médici

et al. 2015

Biotechnology Advances

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“…It is known that sulfate ions usually interact with sites of protein for binding of phosphate groups, including internucleoside phosphate groups of DNA [51][52][53]. The analysis of the available crystalline structures of the LA in the PDB database made it possible to detect the presence of two sites of LA binding sulfate ions (PDB 1HML and 3B0I structures).…”

Section: Construction Of the Model Of La Interaction With Onsmentioning

confidence: 99%

How Human Alpha-lactalbumin Recognize DNA and RNA

Ga¹,

Li²,

Nv³

et al. 2018

Biochem Anal Biochem

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Human α-lactalbumin (LA) has an important function in mammary cells, activates the caspases involving in apoptosis. LA complex interacts with DNA in tumor cells with histones and impaired the chromatin structure. There are no any data on how LA recognizes DNA and interact with histones and DNA of chromatin. The approach of stepwise increase in ligand complexity was used for estimation of the relative contribution of every DNA nucleotide unit to its total affinity for human LA. It was shown that the LA DNA-binding site minimal ligands are orthophosphate and all dNMPs and rNMPs (K d =(5.0-43)×10 -5 ). Maximal contribution to the total affinity was observed for three nucleotide units of all (pN) n with a significant decrease in the order 1>2>3, at n=4-6 it was remarkably lower and at n ≥ 6-7 all dependencies of -logK d upon n reached plateaus. Double-stranded (pN) n showed significantly lower affinity comparing with singlestranded ligands. The thermodynamic parameters characterizing the specific contribution of (pN) 1-6 every nucleotide link (ΔG o ) to their total affinity for LA were estimated. The spatial model of LA-DNA complex was calculated. LA protein sequence has homology with those of five histones (H1-H4) involved in the chromatin nucleus interactions between themselves and their complex with DNA. It is assumed that the homology may be the main reason for the interaction of LA with chromatin DNA, leading to a breakdown in its structure, as well as the proper binding of histones between themselves and with DNA.

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“…For example, 2,6-diaminopurine-deoxynucleoside-5'-monophosphate (dDAMP) was deaminated via adenylate deaminase to form dGMP. Recently, a new active chimera phosphodeoxyribosyltransferase (PDTase) was designed to convert guanine into dGMP from dAMP [6]. However, in these novel processes, dGMP could not be produced in large scales because the original substrates were too expensive.…”

Section: Introductionmentioning

confidence: 99%

One-pot process of 2′-deoxyguanylic acid catalyzed by a multi-enzyme system

Ding

et al. 2015

Biotechnol Bioproc E

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2'-Deoxyguanylic acid (deoxyguanosine-5'-monophosphate, dGMP) is a substance required by living cells that is used extensively in reagents, fine chemicals and other industrial fields. Traditionally, dGMP is separated from DNA degradation products, which is low-yielding and time-consuming. Herein, we investigated a novel, onepot multi-enzymatic cascade reaction to produce dGMP. This reaction involved purine nucleoside phosphorylase (PNPase) and acetate kinase (ACKase) from Escherichia coli, N-deoxyribosytransferase II (NDT-II) from Lactobacillus delbrueckii and deoxyguanosine kinase (dGKase) from Bacillus subtilis. During the reaction, the initial guanosine substrate was cleaved into guanine and ribose-1-phosphate by PNPase. Then, deoxyguanosine (dGR) was subsequently produced from a reaction between guanine and thymidine catalysed by NDT-II. Finally, the intermediate dGR was phosphorylated to dGMP by dGKase and a cytidine triphosphate (CTP) regeneration system that utilised acetyl phosphate via ACKase. A very small amount of CTP was added because CTP regeneration was efficient to transfer a phosphate group from acetyl phosphate to dGR. After 12 h of incubation, a maximal dGMP yield of up to 76% was obtained based on the addition of 5 mM guanosine and 5 mM thymidine.

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Phosphodeoxyribosyltransferases, Designed Enzymes for Deoxyribonucleotides Synthesis

Cited by 14 publications

References 48 publications

Biocatalytic approaches applied to the synthesis of nucleoside prodrugs

Biocatalytic approaches applied to the synthesis of nucleoside prodrugs

How Human Alpha-lactalbumin Recognize DNA and RNA

One-pot process of 2′-deoxyguanylic acid catalyzed by a multi-enzyme system

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