Revealing the unknown aspects of initial steps of prenylated flavin mononucleotide biosynthesis – the role of Lys129 in PaUbiX

Background Prenylated flavin mononucleotide (prFMN) is a recently discovered, heavily modified flavin compound. It is the only known cofactor that enables enzymatic 1,3-dipolar cycloaddition reactions. It is produced by enzymes from UbiX family, from flavin mononucleotide and either dimethylallyl mono- or diphosphate. prFMN biosynthesis is currently reported to be initiated by a protonation of the substrate by Glu140. Methods Computational chemistry methods are applied herein - mostly different flavors of molecular dynamics MD, such as Constant pH MD, hybrid Quantum-Mechanical / Molecular Mechanical MD, and classical MD. Results Glu140 competes for a single proton with Lys129 but it is the latter that adopted a protonated state throughout most of the simulation time. Lys129 plays a key role in the positioning of the DMAP’s phosphate group within the PaUbiX active site. DMAP’s breakdown into a phosphate and a prenyl group can be decoupled from the protona-tion of the DMAP’s phosphate group. Conclusions The role of Lys129 in functioning of PaUbiX is reported for the first time. The severity of interactions between Glu140, Lys129, and DMAP’s phosphate group enables an unusual decoupling of phosphate’s protonation from DMAP’s breakdown. Those findings are most likely conserved throughout the UbiX family to the structural re-semblence of active sites of those proteins. Significance Mechanistic insights into a crucial biochemical process, biosynthesis of prFMN, are provided. This study, alt-hough purely computational, extends and perfectly complements the knowledge obtained in classical laboratory experiments.

Phosphate group functionalized magnetic metal–organic framework nanocomposite for highly efficient removal of U(VI) from aqueous solution

The phosphate group functionalized metal-organic frameworks (MOFs) as the adsorbent for removal of U(VI) from aqueous solution still suffer from low adsorption efficiency, due to the low grafting rate of groups into the skeleton structure. Herein, a novel phosphate group functionalized metal–organic framework nanoparticles (denoted as Fe3O4@SiO2@UiO-66-TPP NPs) designed and prepared by the chelation between Zr and phytic acid, showing fast adsorption rate and outstanding selectivity in aqueous media including 10 coexisting ions. The Fe3O4@SiO2@UiO-66-TPP was properly characterized by TEM, FT-IR, BET, VSM and Zeta potential measurement. The removal performance of Fe3O4@SiO2@UiO-66-TPP for U(VI) was investigated systematically using batch experiments under different conditions, including solution pH, incubation time, temperature and initial U(VI) concentration. The adsorption kinetics, isotherm, selectivity studies revealed that Fe3O4@SiO2@UiO-66-TPP NPs possess fast adsorption rates (approximately 15 min to reach equilibrium), high adsorption capacities (307.8 mg/g) and outstanding selectivity (Su = 94.4%) towards U(VI), which in terms of performance are much better than most of the other magnetic adsorbents. Furthermore, the adsorbent could be reused for U(VI) removal without obvious loss of adsorption capacity after five consecutive cycles. The research work provides a novel strategy to assemble phosphate group-functionalized MOFs.

ChoKs as a Promising Therapeutic Target for a Variety of Pathologies

Alterations in cell metabolism represent a common cause of human diseases. Changes in lipid profiles are not an exception to this rule, including those lipids that are produced via the choline kinase (ChoK) pathway. ChoK catalyzes the conversion of choline to phosphocholine via the transfer of a phosphate group from ATP to choline.

Structural Insights into Protein Regulation by Phosphorylation and Substrate Recognition of Protein Kinases/Phosphatases

Protein phosphorylation is one of the most widely observed and important post-translational modification (PTM) processes. Protein phosphorylation is regulated by protein kinases, each of which covalently attaches a phosphate group to an amino acid side chain on a serine (Ser), threonine (Thr), or tyrosine (Tyr) residue of a protein, and by protein phosphatases, each of which, conversely, removes a phosphate group from a phosphoprotein. These reversible enzyme activities provide a regulatory mechanism by activating or deactivating many diverse functions of proteins in various cellular processes. In this review, their structures and substrate recognition are described and summarized, focusing on Ser/Thr protein kinases and protein Ser/Thr phosphatases, and the regulation of protein structures by phosphorylation. The studies reviewed here and the resulting information could contribute to further structural, biochemical, and combined studies on the mechanisms of protein phosphorylation and to drug discovery approaches targeting protein kinases or protein phosphatases.

Synthesis of phosphorus-containing pseudopoliamino acids of polyester type

The method of obtaining phosphorus-containing polyester by the Steglich reaction is considered. The results of studies on the production of polyesteresters using ethyl phosphate group in the structure of dipolyethyleneglycolethylphosphate are presented. The obtained polymer was characterized by IR and 1H NMR spectroscopy. The composition of polyester ether was evaluated and its end groups were analyzed.

Research progress in the mining technology of the slowly inclined, thin to medium thick phosphate rock transition from open-pit to underground mine

This paper takes the deep ore body of Yunnan Phosphate Group Co. Ltd, the largest open-pit chemical mining enterprise in China, as the research background, and systematically introduces the technical problems recognised by many Chinese researchers in the past eight years on the open-pit to underground mining of gently inclined thin to medium-thick ore bodies with a soft interlayer. It shows that the mining of open-pit transferred to underground is a complex engineering system, and the underground stope surrounding rock and overlying strata present a nonlinear failure process. Through mining process innovation, mining method innovation and improvement, research was undertaken on new processes and technologies for phosphorus mining under complex conditions. The relevant research results not only have important economic value and academic significance for Yunnan Phosphate Group Co. Ltd. but also have important guidance and impetus to the exploitation of a large number of similar phosphate resources in China.

Construction of a reduction-responsive oligonucleotide via a post-modification approach utilizing 4-nitrophenyl diazomethane

Herein, we describe the construction of a reduction-responsive oligonucleotide by post-modification of an oligonucleotide with a diazo compound bearing a 4-nitrobenzyl group as a reduction-responsive cleavable moiety. High-performance liquid chromatography and mass spectrometry were used to reveal the introduction of a 4-nitrobenzyl group to the 5′-phosphate group of an oligonucleotide, and the subsequent reduction-triggered recovery of the original oligonucleotide. The protocol used for the preparation of this reduction-responsive oligonucleotide is simple and it will have various applications in the fields of chemical and synthetic biology.