scholarly journals ATP emerged to induce protein folding, inhibit aggregation and increase stability

2019 ◽  
Author(s):  
Jian Kang ◽  
Liangzhong Lim ◽  
Jianxing Song
Keyword(s):  
Protein Folding ◽  
Small Molecules ◽  
Origin Of Life ◽  
Protein Homeostasis ◽  
Nmr Characterization ◽  
General Capacity ◽  
The Origin Of Life ◽  
First Time ◽  
Control Protein

AbstractBy NMR characterization of effects of ATP and related molecules on the folding and dynamics of the ALS-causing C71G-PFN1 and nascent hSOD1, we reveal for the first time that ATP has a general capacity in inducing protein folding with the highest efficiency known so far. This capacity was further identified to result from triphosphate, a key intermediate in prebiotic chemistry, which, however, can severely trigger protein aggregation. Remarkably, by joining adenosine and triphosphate together, ATP integrates three abilities to simultaneously induce protein folding, inhibit aggregation and increase thermodynamic stability. Our study implies that the emergence of ATP might represent an irreplaceable step essential for the Origin of Life, and decrypts a principle for engineering small molecules with three functions to treat aggregation-associated ageing and diseases.One sentence summaryBy joining adenosine and triphosphate, ATP integrates three abilities to control protein homeostasis for the Origin of Life.

scholarly journals ATP induces protein folding, inhibits aggregation and antagonizes destabilization by effectively mediating water-protein-ion interactions, the heart of protein folding and aggregation

2020 ◽  
Author(s):  
Jian Kang ◽  
Liangzhong Lim ◽  
Jianxing Song
Keyword(s):  
Protein Folding ◽  
Prebiotic Chemistry ◽  
Specific Binding ◽  
Protein Homeostasis ◽  
Molar Ratios ◽  
Ion Interactions ◽  
Regulate Protein ◽  
First Time ◽  
Control Protein ◽  
Liquid Liquid Phase Separation

AbstractMany, particularly β-dominant proteins, are prone to misfolding/aggregation in the crowded cells, a hallmark of ageing and neurodegenerative diseases including ALS. ATP provides energy to drive supramolecular machineries to control protein hemostasis in modern cells. Recently ATP was decoded to hydrotropically inhibit/dissolve liquid-liquid phase separation (LLPS) and aggregation/fibrillation at millimolar concentrations. We also found that by specific binding, ATP induces and subsequently dissolves LLPS, as well as inhibits fibrillation. Nevertheless, no report shows that ATP can directly induce protein folding. Here, by selecting two aggregation-prone ALS-causing proteins with the unfolded states, we successfully visualized the effects of ATP and 11 molecules with NMR directly on their folding and aggregation. The study reveals for the first time that ATP can induce folding at molar ratios of 2-8, the highest efficiency known so far. Intriguingly, this inducing-capacity comes from triphosphate, a key intermediate in prebiotic chemistry, which, however, also triggers aggregation. Most unexpectedly, upon joining with adenosine, the ability of triphosphate to trigger aggregation is shielded. Marvelously, ATP emerged to manifest three integrated abilities: to induce folding, inhibit aggregation and increase stability, that are absent in ATPP, AMP-PCP and AMP-PNP. Our study sheds the first light on previously-unknown roles of ATP in energy-independently controlling protein folding and aggregation by effectively mediating water-protein-ion interactions. Therefore, ATP might be not just irreplaceable for solving protein folding and aggregation problems simultaneously in primitive cells for Origin of Life, but also energy-independently operating in modern cells to regulate protein homeostasis fundamentally critical for physiology and pathology.

scholarly journals Optimized methods for IL-17A refolding and anti-IL17A Fab production for co-crystallization with small molecules

BioTechniques ◽  
2020 ◽  
Vol 69 (1) ◽  
pp. 70-76
Author(s):  
Xiaoyun Meng ◽  
Lanjun Zhang ◽  
Hong Wei ◽  
Furong Li ◽  
Lihua Hu ◽  
...  
Keyword(s):  
Drug Discovery ◽  
Small Molecules ◽  
Small Molecule ◽  
Yield Enhancement ◽  
High Affinity ◽  
Interleukin 17A ◽  
Affinity Peptide ◽  
First Time ◽  
Essential Prerequisite

Refolding of human interleukin 17A (IL-17A) has been reported; however, the key refolding protocol was not robust enough to deliver consistent results and to be easily scaled up for crystallization. Here we report an optimized refolding method for IL-17A. Although co-crystal structures of IL-17A with ligands have been obtained with a high-affinity peptide and an anti-IL-17A Fab as stabilizers, neither the production yield nor the characterization of the IL-17A/Fab complex was reported. To facilitate co-crystallization of IL-17A with small-molecule compounds derived from our DNA encoded library, we also describe the method for yield enhancement of anti-IL-17A Fab production and characterize the IL-17A/Fab complex for the first time, providing an essential prerequisite for structure-based drug discovery targeting IL-17A.

scholarly journals Rapid Rubber Extraction and NMR Spectroscopy of Rubber, Extracted from the Endemic Species Scorzonera Tau-Saghyz

2020 ◽  
Vol 22 (1) ◽  
pp. 59
Author(s):  
K.K. Boguspaev ◽  
S.K. Turasheva ◽  
T.M. Seilkhanov ◽  
D.G. Faleev ◽  
M.S. Mutalkhanov ◽  
...  
Keyword(s):  
Adventitious Shoots ◽  
Physiological Age ◽  
Root Extract ◽  
Nmr Characterization ◽  
First Time ◽  
Rubber Good ◽  
Isoprene Rubber

Scorzonera tau-saghyz Lipsch. et G.G. Bosse is an endemic rubber producing plant, growing in mountain regions in South Kazakhstan. The rubber content in plants and the quality of biopolymer has an important impact on industrial rubber production. The results of this study showed that the amount of rubber in S. tau-saghyz roots fluctuates between 7.74% and 38.75%. The amount of synthesized and deposited rubber biopolymer particles depends on various factors such as physiological age of plant, origin, temperature, moisture and environmental conditions. We optimized the extraction method of natural rubber by using n-hexane as a solvent for direct extraction. This method allows extracting the maximum amount of rubber from 3‒4-year-old plants. NMR results show structural links of natural isoprene rubber in the root extract sample. There is a clear relationship between methyl, methine and methylene protons which corresponds to isoprene rubber structure. The samples having strongly marked singlets that are inherent for rubber functional groups confirms the stereospecific structure of rubber. Good solubility of the root extract in deuterated chloroform can characterize the low molecular weight of the polymer. NMR characterization of rubber, extracted from S. tau-saghyz roots, is reported for the first time. Regeneration in vitro provides an important opportunity for endemic preservation by rapidly increasing the number of plants. The best regeneration of adventitious shoots was obtained on MS medium containing 5.5 μM kinetin and 0.5 μM NAA. The plants were successfully acclimatized in a glasshouse with 75% of S. tau-saghyz plantlets, respectively surviving after transfer to ex vitro conditions.

Real-Time NMR Characterization of Structure and Dynamics in a Transiently Populated Protein Folding Intermediate

2012 ◽  
Vol 134 (19) ◽  
pp. 8066-8069 ◽  
Author(s):  
Enrico Rennella ◽  
Thomas Cutuil ◽  
Paul Schanda ◽  
Isabel Ayala ◽  
Vincent Forge ◽  
...  
Keyword(s):  
Protein Folding ◽  
Real Time ◽  
Folding Intermediate ◽  
Structure And Dynamics ◽  
Nmr Characterization

scholarly journals Unraveling the History and Revisiting the Synthesis of Degradable Polystyrene Analogues via Radical Ring-Opening Copolymerization with Cyclic Ketene Acetals

Materials ◽  
2020 ◽  
Vol 13 (10) ◽  
pp. 2325
Author(s):  
Alexander W. Jackson ◽  
Srinivasa Reddy Mothe ◽  
Lohitha Rao Chennamaneni ◽  
Alexander van Herk ◽  
Praveen Thoniyot
Keyword(s):  
Ring Opening ◽  
Hydrolytic Degradation ◽  
Degradation Pathway ◽  
Historical Record ◽  
Radical Ring ◽  
Nmr Characterization ◽  
Cyclic Ketene Acetals ◽  
Ketene Acetals ◽  
First Time

Degradable analogues of polystyrene are synthesized via radical ring-opening (co)polymerization (rROP) between styrene and two cyclic ketene acetals, namely 2-methylene-1,3-dioxepane (MDO) and 5,6-benzo-2-methylene-1,3-dioxepane (BMDO). This approach periodically inserts ester bonds throughout the main chain of polystyrene, imparting a degradation pathway via ester hydrolysis. We discuss the historical record of this approach, with careful attention paid to the conflicting findings previously reported. We have found a common 1H NMR characterization error, repeated throughout the existing body of work. This misinterpretation is responsible for the discrepancies within the cyclic ketene acetal (CKA)-based degradable polystyrene literature. These inconsistencies, for the first time, are now understood and resolved through optimization of the polymerization conditions, and detailed characterization of the degradable copolymers and their corresponding oligomers after hydrolytic degradation.

A combined solid-state 17O NMR, crystallographic, and computational study of oxiranes

2020 ◽  
Vol 98 (8) ◽  
pp. 434-440
Author(s):  
Andrew Rinald ◽  
Victor Terskikh ◽  
Gabriele Schatte ◽  
Gang Wu
Keyword(s):  
Solid State ◽  
Bond Angle ◽  
Computational Study ◽  
X Ray Crystallography ◽  
Constrained Geometry ◽  
Nmr Characterization ◽  
Quadrupole Coupling ◽  
Nmr Tensors ◽  
First Time

We report the synthesis and solid-state 17O NMR characterization of three 17O-labeled oxiranes: (2S*,3S*)-2,3-bis(4-nitrophenyl)-[17O]oxirane, (2S*,3R*)-2,3-bis(4-nitrophenyl)-[17O]oxirane, and 2,2,3-triphenyl-[17O]oxirane. In addition, we have determined the crystal structure of (2S*,3R*)-2,3-bis(4-nitrophenyl)oxirane by X-ray crystallography. When the experimentally determined 17O NMR tensors for oxiranes (where the C–O–C bond angle is about 60°) are compared with those for dimethyl ether (where the C–O–C bond angle is 113°) and other R–O–R′ functional groups, we found that the highly constrained geometry of oxiranes results in distinct tensor orientations in the molecular frame of reference. The experimental results are complemented by quantum chemical computations. This study represents the first time that 17O chemical shift and quadrupole coupling tensors are simultaneously determined for oxirane compounds.

scholarly journals Questions and Answers Related to the Prebiotic Production of Oligonucleotide Sequences from 3′,5′ Cyclic Nucleotide Precursors

Life ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 800
Author(s):  
Judit E. Šponer ◽  
Jiří Šponer ◽  
Aleš Kovařík ◽  
Ondrej Šedo ◽  
Zbyněk Zdráhal ◽  
...  
Keyword(s):  
Origin Of Life ◽  
Cyclic Nucleotides ◽  
Cyclic Nucleotide ◽  
Prebiotic Chemistry ◽  
Current Review ◽  
Questions And Answers ◽  
Template Free ◽  
The Origin Of Life ◽  
Geological Context

Template-free nonenzymatic polymerization of 3′,5′ cyclic nucleotides is an emerging topic of the origin of life research. In the last ten years, a number of papers have been published addressing various aspects of this process. These works evoked a vivid discussion among scientists working in the field of prebiotic chemistry. The aim of the current review is to answer the most frequently raised questions related to the detection and characterization of oligomeric products as well as to the geological context of this chemistry.

scholarly journals Spectroscopic Characterization of Key Aromatic and Heterocyclic Molecules: A Route toward the Origin of Life

2017 ◽  
Vol 154 (3) ◽  
pp. 82 ◽  
Author(s):  
Cristina Puzzarini ◽  
Alberto Baiardi ◽  
Julien Bloino ◽  
Vincenzo Barone ◽  
Thomas E. Murphy ◽  
...  
Keyword(s):  
Origin Of Life ◽  
Spectroscopic Characterization ◽  
Heterocyclic Molecules ◽  
The Origin Of Life

scholarly journals A framework for parsing heritable information

2020 ◽  
Vol 17 (165) ◽  
pp. 20200154 ◽  
Author(s):  
Antony M. Jose
Keyword(s):  
Small Molecules ◽  
Origin Of Life ◽  
Living Systems ◽  
Gene Sequences ◽  
Amount Of Information ◽  
Relevant Property ◽  
Complex Development ◽  
Sensor Property ◽  
The Origin Of Life ◽  
Successive Generations

Living systems transmit heritable information using the replicating gene sequences and the cycling regulators assembled around gene sequences. Here, I develop a framework for heredity and development that includes the cycling regulators parsed in terms of what an organism can sense about itself and its environment by defining entities, their sensors and the sensed properties. Entities include small molecules (ATP, ions, metabolites, etc.), macromolecules (individual proteins, RNAs, polysaccharides, etc.) and assemblies of molecules. While concentration may be the only relevant property measured by sensors for small molecules, multiple properties that include concentration, sequence, conformation and modification may all be measured for macromolecules and assemblies. Each configuration of these entities and sensors that is recreated in successive generations in a given environment thus specifies a potentially vast amount of information driving complex development in each generation. This entity–sensor–property framework explains how sensors limit the number of distinguishable states, how distinct molecular configurations can be functionally equivalent and how regulation of sensors prevents detection of some perturbations. Overall, this framework is a useful guide for understanding how life evolves and how the storage of information has itself evolved with complexity since before the origin of life.

The Birth of Living Radium

2007 ◽  
Vol 97 (1) ◽  
pp. 1-27 ◽  
Author(s):  
Luis Campos
Keyword(s):  
Twentieth Century ◽  
Origin Of Life ◽  
Half Life ◽  
Biological Research ◽  
Early Twentieth Century ◽  
The Origin Of Life

This article traces the half-life of a series of provocative and productive interconnections between radium, radioactivity, and life in the early twentieth century. Examining the metaphysics of metaphor set in motion by a widespread discourse of "living radium" among physicists and a radium-crazed public alike, I suggest how such conceptions may ultimately have shaped fundamental biological research into the origin of life, the nature of mutation, and even the characterization of the gene.

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