Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Trivalent rare earth metal cofactors confer rapid NP-DNA polymerase activity.

ABSTRACT: A DNA polymerase with a single mutation and a divalent calcium cofactor catalyzes the synthesis of unnatural N3'→P5' phosphoramidate (NP) bonds to form NP-DNA. However, this template-directed phosphoryl transfer activity remains orders of magnitude slower than native phosphodiester synthesis. Here, we used time-resolved x-ray crystallography to show that NP-DNA synthesis proceeds with a single detectable calcium ion in the active site. Using insights from isotopic and elemental effects, we propose that one-metal-ion electrophilic substrate activation is inferior to the native two-metal-ion mechanism. We found that this deficiency in divalent activation could be ameliorated by trivalent rare earth and post-transition metal cations, substantially enhancing NP-DNA synthesis. Scandium(III), in particular, confers highly specific NP activity with kinetics enhanced by more than 100-fold over calcium(II), yielding NP-DNA strands up to 100 nucleotides in length.

SUBMITTER: Lelyveld VS

PROVIDER: S-EPMC10886449 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Trivalent rare earth metal cofactors confer rapid NP-DNA polymerase activity.

Lelyveld Victor S VS Fang Ziyuan Z Szostak Jack W JW

Science (New York, N.Y.) 20231026 6669

A DNA polymerase with a single mutation and a divalent calcium cofactor catalyzes the synthesis of unnatural N3'→P5' phosphoramidate (NP) bonds to form NP-DNA. However, this template-directed phosphoryl transfer activity remains orders of magnitude slower than native phosphodiester synthesis. Here, we used time-resolved x-ray crystallography to show that NP-DNA synthesis proceeds with a single detectable calcium ion in the active site. Using insights from isotopic and elemental effects, we propo ...[more]

PMID: 37883544

Similar Datasets

Oxidoreductases and metal cofactors in the functioning of the earth.

Project description:Life sustains itself using energy generated by thermodynamic disequilibria, commonly existing as redox disequilibria. Metals are significant players in controlling redox reactions, as they are essential components of the engine that life uses to tap into the thermodynamic disequilibria necessary for metabolism. The number of proteins that evolved to catalyze redox reactions is extraordinary, as is the diversification level of metal cofactors and catalytic domain structures involved. Notwithstanding the importance of the topic, the relationship between metals and the redox reactions they are involved in has been poorly explored. This work reviews the structure and function of different prokaryotic organometallic-protein complexes, highlighting their pivotal role in controlling biogeochemistry. We focus on a specific subset of metal-containing oxidoreductases (EC1 or EC7.1), which are directly involved in biogeochemical cycles, i.e., at least one substrate or product is a small inorganic molecule that is or can be exchanged with the environment. Based on these inclusion criteria, we select and report 59 metalloenzymes, describing the organometallic structure of their active sites, the redox reactions in which they are involved, and their biogeochemical roles.

| S-EPMC10423856 | biostudies-literature

Synthesis of rare-earth metal and rare-earth metal-fluoride nanoparticles in ionic liquids and propylene carbonate.

Project description:Decomposition of rare-earth tris(N,N'-diisopropyl-2-methylamidinato)metal(III) complexes [RE{MeC(N(iPr)2)}3] (RE(amd)3; RE = Pr(III), Gd(III), Er(III)) and tris(2,2,6,6-tetramethyl-3,5-heptanedionato)europium(III) (Eu(dpm)3) induced by microwave heating in the ionic liquids (ILs) 1-butyl-3-methylimidazolium tetrafluoroborate ([BMIm][BF4]), 1-butyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide ([BMIm][NTf2]) and in propylene carbonate (PC) yield oxide-free rare-earth metal nanoparticles (RE-NPs) in [BMIm][NTf2] and PC for RE = Pr, Gd and Er or rare-earth metal-fluoride nanoparticles (REF3-NPs) in the fluoride-donating IL [BMIm][BF4] for RE = Pr, Eu, Gd and Er. The crystalline phases and the absence of significant oxide impurities in RE-NPs and REF3-NPs were verified by powder X-ray diffraction (PXRD), selected area electron diffraction (SAED) and high-resolution X-ray photoelectron spectroscopy (XPS). The size distributions of the nanoparticles were determined by transmission electron microscopy (TEM) and high-angle annular dark-field scanning transmission electron microscopy (HAADF-STEM) to an average diameter of (11 ± 6) to (38 ± 17) nm for the REF3-NPs from [BMIm][BF4]. The RE-NPs from [BMIm][NTf2] or PC showed diameters of (1.5 ± 0.5) to (5 ± 1) nm. The characterization was completed by energy-dispersive X-ray spectroscopy (EDX).

| S-EPMC6036975 | biostudies-literature

Catalytic properties of trivalent rare-earth oxides with intrinsic surface oxygen vacancy.

Project description:Oxygen vacancy (Ov) is an anionic defect widely existed in metal oxide lattice, as exemplified by CeO2, TiO2, and ZnO. As Ov can modify the band structure of solid, it improves the physicochemical properties such as the semiconducting performance and catalytic behaviours. We report here a new type of Ov as an intrinsic part of a perfect crystalline surface. Such non-defect Ov stems from the irregular hexagonal sawtooth-shaped structure in the (111) plane of trivalent rare earth oxides (RE2O3). The materials with such intrinsic Ov structure exhibit excellent performance in ammonia decomposition reaction with surface Ru active sites. Extremely high H2 formation rate has been achieved at ~1 wt% of Ru loading over Sm2O3, Y2O3 and Gd2O3 surface, which is 1.5-20 times higher than reported values in the literature. The discovery of intrinsic Ov suggests great potentials of applying RE oxides in heterogeneous catalysis and surface chemistry.

| S-EPMC11233603 | biostudies-literature

Emerging superconductivity rules in rare-earth and alkaline-earth metal hydrides.

Project description:Hydrides of alkaline-earth and rare-earth metals have garnered significant interest in high-temperature superconductor research due to their excellent electron-phonon coupling and high T c upon pressurization. This study explores the electronic structures and electron-phonon coupling of metal hydrides XHn (n = 4,6), where X includes Ca, Mg, Sc, and Y. The involvement of d-orbital electrons alters the Fermi surface, leading to saddle-point nesting and a charge density wave (CDW) phase transition, which opens the superconducting gap. For instance, in YH6, the exchange coupling between Y-4d and H-1s holes in the phonon softening region results in T c values up to 230 K. The study suggests that factors, such as the origin of the CDW order, hydrogen concentration, and d-orbital contributions are crucial to superconductivity. This work proposes a new rule for high T c superconductors, emphasizing the importance of double gaps and electron-phonon interactions at exchange coupling sites, and predicts potential high-quality superconductors among rare-earth hydrides.

| S-EPMC11342274 | biostudies-literature

Rare-earth metal catalysts for high-pressure synthesis of rare diamonds.

Project description:The combination of the unique properties of diamond and the prospects for its high-technology applications urges the search for new solvents-catalysts for the synthesis of diamonds with rare and unusual properties. Here we report the synthesis of diamond from melts of 15 rare-earth metals (REM) at 7.8 GPa and 1800-2100 °C. The boundary conditions for diamond crystallization and the optimal parameters for single crystal diamond synthesis are determined. Depending on the REM catalyst, diamond crystallizes in the form of cube-octahedrons, octahedrons and specific crystals bound by tetragon-trioctahedron and trigon-trioctahedron faces. The synthesized diamonds are nitrogen-free and belong to the rare type II, indicating that the rare-earth metals act as both solvent-catalysts and nitrogen getters. It is found that the REM catalysts enable synthesis of diamond doped with group IV elements with formation of impurity-vacancy color centers, promising for the emerging quantum technologies. Our study demonstrates a new field of application of rare-earth metals.

| S-EPMC8055970 | biostudies-literature

Heteroatom-assisted olefin polymerization by rare-earth metal catalysts.

Project description:Heteroatom-functionalized polyolefins are of fundamental interest and practical importance. This has spurred investigations of the copolymerization of polar and nonpolar olefins. We report the first syndiospecific polymerization of a series of heteroatom-containing α-olefins and their copolymerization with ethylene catalyzed by half-sandwich rare-earth complexes. We have found that the interaction between a heteroatom in a functional α-olefin monomer and a rare-earth metal catalyst can significantly raise the olefin polymerization activity and thereby promote its copolymerization with ethylene. By using this heteroatom-assisted olefin polymerization (HOP) strategy, we have successfully synthesized a series of heteroatom (O, S, Se, N, and P)-functionalized polyolefins with high molecular weights and controllable functional monomer contents. The mechanistic aspect of the HOP process has been elucidated by computational studies. We expect that our findings will guide the design of new catalyst systems for the synthesis of various desired functional polyolefins.

| S-EPMC5521993 | biostudies-literature

Structurally triggered metal-insulator transition in rare-earth nickelates.

Project description:Rare-earth nickelates form an intriguing series of correlated perovskite oxides. Apart from LaNiO3, they exhibit on cooling a sharp metal-insulator electronic phase transition, a concurrent structural phase transition, and a magnetic phase transition toward an unusual antiferromagnetic spin order. Appealing for various applications, full exploitation of these compounds is still hampered by the lack of global understanding of the interplay between their electronic, structural, and magnetic properties. Here we show from first-principles calculations that the metal-insulator transition of nickelates arises from the softening of an oxygen-breathing distortion, structurally triggered by oxygen-octahedra rotation motions. The origin of such a rare triggered mechanism is traced back in their electronic and magnetic properties, providing a united picture. We further develop a Landau model accounting for the metal-insulator transition evolution in terms of the rare-earth cations and rationalizing how to tune this transition by acting on oxygen rotation motions.

| S-EPMC5700091 | biostudies-literature

Insights into the effect of minor groove interactions and metal cofactors on mutagenic replication by human DNA polymerase β.

Project description:DNA polymerases accommodate various base-pair conformations in the event of incorrect insertions. In particular, Watson-Crick-like dG:dTTP base pair has been observed at the insertion site of human DNA polymerase β (pol β). A potential factor contributing to the diverse conformations of base-pair mismatches is minor groove interactions. To gain insights into the effect of minor groove interactions on base-pair conformations, we generated an Asn279Ala polβ mutant that cannot make minor groove contacts with an incoming nucleotide. We conducted structural and kinetic studies of Asn279Ala polβ in complex with incoming dTTP and templating dG or O6-methyl-dG. The crystal structure of the Asn279Ala polβ-G:T complex showed a wobble dG:dTTP base pair, indicating that the previously observed Watson-Crick-like dG:dTTP conformation was induced by the minor groove contact. In contrast, O6-methyl-dG, an analog of the enol tautomer of guanine, formed a Watson-Crick-like base pair with dTTP in the absence of the minor groove contact. These results suggest that the Watson-Crick-like G:T base pair at the insertion site is formed by the rare enol tautomers of G or T, whose population is increased by the minor groove hydrogen bond with Asn279. Kinetic studies showed that Asn279Ala mutation decreased dG:dTTP misincorporation rate six-fold in the presence of Mg2+ but increased the rate three-fold in the presence of Mn2+, highlighting the effect of minor groove interactions and metal ions on promutagenic replication by polβ.

| S-EPMC6048017 | biostudies-literature

Dramatic Enhancement of Rare-Earth Metal-Organic Framework Stability Via Metal Cluster Fluorination.

Project description:Rare-earth polynuclear metal-organic frameworks (RE-MOFs) have demonstrated high durability for caustic acid gas adsorption and separation based on gas adsorption to the metal clusters. The metal clusters in the RE-MOFs traditionally contain RE metals bound by μ3-OH groups connected via organic linkers. Recent studies have suggested that these hydroxyl groups could be replaced by fluorine atoms during synthesis that includes a fluorine-containing modulator. Here, a combined modeling and experimental study was undertaken to elucidate the role of metal cluster fluorination on the thermodynamic stability, structure, and gas adsorption properties of RE-MOFs. Through systematic density-functional theory calculations, fluorinated clusters were found to be thermodynamically more stable than hydroxylated clusters by up to 8-16 kJ/mol per atom for 100% fluorination. The extent of fluorination in the metal clusters was validated through a 19F NMR characterization of 2,5-dihydroxyterepthalic acid (Y-DOBDC) MOF synthesized with a fluorine-containing modulator. 19F magic-angle spinning NMR identified two primary peaks in the isotropic chemical shift (δiso) spectra located at -64.2 and -69.6 ppm, matching calculated 19F NMR δiso peaks at -63.0 and -70.0 ppm for fluorinated systems. Calculations also indicate that fluorination of the Y-DOBDC MOF had negligible effects on the acid gas (SO2, NO2, H2O) binding energies, which decreased by only ∼4 kJ/mol for the 100% fluorinated structure relative to the hydroxylated structure. Additionally, fluorination did not change the relative gas binding strengths (SO2 > H2O > NO2). Therefore, for the first time the presence of fluorine in the metal clusters was found to significantly stabilize RE-MOFs without changing their acid-gas adsorption properties.

| S-EPMC9400048 | biostudies-literature

Enhanced rare-earth separation with a metal-sensitive lanmodulin dimer.

Project description:Technologically critical rare-earth elements are notoriously difficult to separate, owing to their subtle differences in ionic radius and coordination number1-3. The natural lanthanide-binding protein lanmodulin (LanM)4,5 is a sustainable alternative to conventional solvent-extraction-based separation6. Here we characterize a new LanM, from Hansschlegelia quercus (Hans-LanM), with an oligomeric state sensitive to rare-earth ionic radius, the lanthanum(III)-induced dimer being >100-fold tighter than the dysprosium(III)-induced dimer. X-ray crystal structures illustrate how picometre-scale differences in radius between lanthanum(III) and dysprosium(III) are propagated to Hans-LanM's quaternary structure through a carboxylate shift that rearranges a second-sphere hydrogen-bonding network. Comparison to the prototypal LanM from Methylorubrum extorquens reveals distinct metal coordination strategies, rationalizing Hans-LanM's greater selectivity within the rare-earth elements. Finally, structure-guided mutagenesis of a key residue at the Hans-LanM dimer interface modulates dimerization in solution and enables single-stage, column-based separation of a neodymium(III)/dysprosium(III) mixture to >98% individual element purities. This work showcases the natural diversity of selective lanthanide recognition motifs, and it reveals rare-earth-sensitive dimerization as a biological principle by which to tune the performance of biomolecule-based separation processes.

| S-EPMC10232371 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data