scholarly journals The role of thermal activation in motion and force generation by molecular motors

2000 ◽  
Vol 355 (1396) ◽  
pp. 511-522 ◽  
Author(s):  
R. Dean Astumian
Keyword(s):  
Molecular Motors ◽  
Atp Hydrolysis ◽  
Force Production ◽  
Hand Model ◽  
Small Load ◽  
Wide Range ◽  
One Step ◽  
The One ◽  
Kinesin Molecule ◽  
Stochastic Properties

The currently accepted mechanism for ATP–driven motion of kinesin is called the hand–over–hand model, where some chemical transition during the ATP hydrolysis cycle stretches a spring, and motion and force production result from the subsequent relaxation. It is essential in this mechanism for the moving head of kinesin to dissociate, while the other head remains firmly attached to the microtubule. Here we propose an alternative Brownian motor model where the action of ATP modulates the interaction potential between kinesin and the microtubule rather than a spring internal to the kinesin molecule alone. In this model neither head need dissociate (which predicts that under some circumstances a single–headed kinesin can display processive motion) and the transitions by which the motor moves are best described as thermally activated steps. This model is consistent with a wide range of experimental data on the force–velocity curves, the one ATP to one–step stoichiometry observed at small load, and the stochastic properties of the stepping.

scholarly journals Structural and Computational Insights into a Blebbistatin-Bound Myosin•ADP Complex with Characteristics of an ADP-Release Conformation along the Two-Step Myosin Power Stoke

2020 ◽  
Vol 21 (19) ◽  
pp. 7417 ◽  
Author(s):  
Wiebke Ewert ◽  
Peter Franz ◽  
Georgios Tsiavaliaris ◽  
Matthias Preller
Keyword(s):  
Atp Hydrolysis ◽  
Hydrolysis Product ◽  
Force Production ◽  
Salt Bridge ◽  
Adenosine Diphosphate ◽  
Power Stroke ◽  
Directed Movement ◽  
Wide Range ◽  
Adp Release ◽  
Dynamics Simulations

The motor protein myosin drives a wide range of cellular and muscular functions by generating directed movement and force, fueled through adenosine triphosphate (ATP) hydrolysis. Release of the hydrolysis product adenosine diphosphate (ADP) is a fundamental and regulatory process during force production. However, details about the molecular mechanism accompanying ADP release are scarce due to the lack of representative structures. Here we solved a novel blebbistatin-bound myosin conformation with critical structural elements in positions between the myosin pre-power stroke and rigor states. ADP in this structure is repositioned towards the surface by the phosphate-sensing P-loop, and stabilized in a partially unbound conformation via a salt-bridge between Arg131 and Glu187. A 5 Å rotation separates the mechanical converter in this conformation from the rigor position. The crystallized myosin structure thus resembles a conformation towards the end of the two-step power stroke, associated with ADP release. Computationally reconstructing ADP release from myosin by means of molecular dynamics simulations further supported the existence of an equivalent conformation along the power stroke that shows the same major characteristics in the myosin motor domain as the resolved blebbistatin-bound myosin-II·ADP crystal structure, and identified a communication hub centered on Arg232 that mediates chemomechanical energy transduction.

Address of the President Lord Todd, O. M. at the Anniversary Meeting, 1 December 1980

1980 ◽  
Vol 211 (1182) ◽  
pp. 1-13 ◽  
Keyword(s):  
Usnic Acid ◽  
Chemical Properties ◽  
Wide Range ◽  
One Step ◽  
Oxidative Processes ◽  
The One ◽  
Physical And Chemical ◽  
Biosynthetic Studies ◽  
And Chemical Properties

The Copley Medal is awarded to Sir Derek Barton, F. R. S. Among Sir Derek Barton's many distinguished contributions to organic chemistry, outstanding is his conception and development of conformational analysis, which represents the most important advance in this century in the understanding of the stereochemistry of organic compounds, and for which he received a Nobel Prize in 1969. Originally devised for cyclohexane derivatives, the concept was rapidly extended to other ring systems, and is of major importance in interpretation of the physical and chemical properties of a wide range of natural products. Sir Derek has also contributed greatly to the understanding of biosynthesis, and in many cases demonstrated the validity of his hypotheses by labelling experiments in vivo . In particular, his ideas on the nature of phenolic coupling, involving one-electron oxidative processes, formed the basis of a very large number of successful biosynthetic studies, especially in the alkaloid field. He has also applied his ideas to the simulation of natural biosynthetic sequences, the one-step synthesis of the complex usnic acid from a simple monocyclic precursor providing one of the most striking examples.

scholarly journals A Straightforward Substitution Strategy to Tune BODIPY Dyes Spanning the Near-Infrared Region via Suzuki–Miyaura Cross-Coupling

Materials ◽  
2018 ◽  
Vol 11 (8) ◽  
pp. 1297 ◽  
Author(s):  
Guanglei Li ◽  
Yu Otsuka ◽  
Takuya Matsumiya ◽  
Toshiyuki Suzuki ◽  
Jianye Li ◽  
...  
Keyword(s):  
Near Infrared ◽  
Cross Coupling ◽  
Cumulus Cells ◽  
Infrared Region ◽  
Quantum Yields ◽  
Nir Dyes ◽  
Wide Range ◽  
One Step ◽  
The One ◽  
First Time

In this study, a series of new red and near-infrared (NIR) dyes derived from 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene (BODIPY) were developed by introducing thiophene and its derivatives to the 3- and 5- positions of the dichloroBODIPY core. For the first time, cyclictriol boronates and N-methyliminodiacetic acid (MIDA) boronate were used as organoboron species to couple with 3,5-dichloroBODIPY via the one-step Suzuki–Miyaura cross-coupling. Six kinds of thieno-expended BODIPY dyes were synthesized in acceptable yields ranging from 31% to 79%. All six dyes showed different absorption and emission wavelengths spanning a wide range (c.a. 600–850 nm) in the red and NIR regions with relatively high quantum yields (19–85%). Cellular imaging of 8-(2,6-dimethylphenyl)-re3,5-di(2-thienyl)-BODIPY (dye 1) was conducted using bovine cumulus cells, and the fluorescence microscopy images indicated that the chromophore efficiently accumulated and was exclusively localized in the cytoplasm, suggesting it could be utilized as a subcellular probe. All six dyes were characterized using 1H-NMR and mass spectrometry.

scholarly journals An insightful myosin structure reveals how actin triggers force production

2014 ◽  
Vol 70 (a1) ◽  
pp. C1056-C1056
Author(s):  
Paola Llinas ◽  
Tatiana Isabet ◽  
Lin Song ◽  
Allan Zhong ◽  
Serena Sirigu ◽  
...  
Keyword(s):  
Conformational Changes ◽  
Molecular Motors ◽  
Structural State ◽  
Atp Hydrolysis ◽  
Mechanical Energy ◽  
Genetic Disorders ◽  
Force Production ◽  
Actin Binding ◽  
Mechanical Coupling ◽  
Hydrolysis Products

Directed force production is essential for life. Allostery is at the heart of the mechanism that cellular nanomotors use to walk, pull or anchor. Such molecular motors are essential for a cell to migrate, to divide and organise the intra-cellular traffic between its compartments. The actin-based motors, myosins, are critical for many of these movements, for muscle contraction, cytokinesis and sophisticated cellular functions such as hearing. Deficit in these motors can lead to a number of human genetic disorders. Force is produced by these motors by the conversion of chemical energy derived from ATP hydrolysis into mechanical energy via the interaction with their track, the actin filament. Biophysical approaches have provided insights into the chemo-mechanical coupling in the actomyosin system. They show how three allosteric sites communicate via relatively small conformational changes in the motor domain that are coupled and amplified by a lever-arm mechanism that produce a working stroke of several nanometers. While ATP binding and hydrolysis are essential for detachment of the motor from its track and its trapping in the pre-stroke conformation, step-wise rebinding to the track triggers controlled release of hydrolysis products upon the working stroke. A reverse motor, myosin VI has been particularly intriguing and informative regarding the force production mechanism. An unpublished structural state not only reveal how trapping of the hydrolysis products stabilize the primed pre-stroke conformation, it also provides insights for the rearrangements triggered by actin to promote Pi release. This new structural state has all the expected features of the Pi release state populated upon motor re-binding to its track. This allows visualization for the first time of the structural rearrangements triggered by actin binding that are coupled to force generation and product release at the beginning of the powerstroke.

scholarly journals Preparation and Antitumor Activity of Betulin Dipropionate and its Composites

2021 ◽  
Vol 12 (5) ◽  
pp. 6873-6894
Keyword(s):  
Cancer Cells ◽  
Water Solubility ◽  
Annexin V ◽  
Birch Bark ◽  
Natural Polymers ◽  
Wide Range ◽  
One Step ◽  
High Cytotoxicity ◽  
Betulin Dipropionate ◽  
The One

Betulin dipropionate is a natural compound with high cytotoxicity toward many cancer cells. The one-step synthesis directly from the birch bark without a separate betulin isolation stage was developed to obtain betulin dipropionate. Due to its composition, betulin dipropionate is a promising drug for treating a wide range of diseases. However, the poor water solubility of this compound has limited its applications. We prepared the composites of betulin dipropionate using two methods: ball milling of the mixtures of betulin dipropionate with synthetic and natural polymers, such as polyvinylpyrrolidone polyethylene glycol, fumed silica, arabinogalactan, and preparation of thin films with arabinogalactan by evaporating the aqueous solutions. These composites showed higher water solubility and improved antitumor properties against ascites carcinoma cells and human lung adenocarcinoma cells compared with the initial substance. Furthermore, the cell viability studies based on Annexin V and Propidium iodide probes confirmed the high proapoptotic effect of betulin dipropionate against cancer cells.

scholarly journals Hydrothermal Synthesis of CeO2-SnO2 Nanoflowers for Improving Triethylamine Gas Sensing Property

Nanomaterials ◽  
2018 ◽  
Vol 8 (12) ◽  
pp. 1025 ◽  
Author(s):  
Dongping Xue ◽  
Yan Wang ◽  
Jianliang Cao ◽  
Zhanying Zhang
Keyword(s):  
Gas Sensing ◽  
Hydrothermal Reaction ◽  
Pure Sno2 ◽  
Characterization Methods ◽  
Working Temperature ◽  
Wide Range ◽  
Sensitivity And Selectivity ◽  
One Step ◽  
The One ◽  
Optimum Working

Developing the triethylamine sensor with excellent sensitivity and selectivity is important for detecting the triethylamine concentration change in the environment. In this work, flower-like CeO2-SnO2 composites with different contents of CeO2 were successfully synthesized by the one-step hydrothermal reaction. Some characterization methods were used to research the morphology and structure of the samples. Gas-sensing performance of the CeO2-SnO2 gas sensor was also studied and the results show that the flower-like CeO2-SnO2 composite showed an enhanced gas-sensing property to triethylamine compared to that of pure SnO2. The response value of the 5 wt.% CeO2 content composite based sensor to 200 ppm triethylamine under the optimum working temperature (310 °C) is approximately 3.8 times higher than pure SnO2. In addition, CeO2-SnO2 composite is also significantly more selective for triethylamine than pure SnO2 and has better linearity over a wide range of triethylamine concentrations. The improved gas-sensing mechanism of the composites toward triethylamine was also carefully discussed.

General Trend of Negative Transference Number in Li Salt/Ionic Liquid Mixtures

2019 ◽  
Author(s):  
Nicola Molinari ◽  
Jonathan P. Mailoa ◽  
Boris Kozinsky
Keyword(s):  
Ionic Liquid ◽  
Transference Number ◽  
Liquid Mixtures ◽  
Single Linkage ◽  
Self Diffusion ◽  
Wide Range ◽  
Single Linkage Cluster ◽  
Concentrated Solution ◽  
The One ◽  
Dynamics Simulations

We show that strong cation-anion interactions in a wide range of lithium-salt/ionic liquid mixtures result in a negative lithium transference number, using molecular dynamics simulations and rigorous concentrated solution theory. This behavior fundamentally deviates from the one obtained using self-diffusion coefficient analysis and agrees well with experimental electrophoretic NMR measurements, which accounts for ion correlations. We extend these findings to several ionic liquid compositions. We investigate the degree of spatial ionic coordination employing single-linkage cluster analysis, unveiling asymmetrical anion-cation clusters. Additionally, we formulate a way to compute the effective lithium charge that corresponds to and agrees well with electrophoretic measurements and show that lithium effectively carries a negative charge in a remarkably wide range of chemistries and concentrations. The generality of our observation has significant implications for the energy storage community, emphasizing the need to reconsider the potential of these systems as next generation battery electrolytes.<br>

A Study on the Rearrangement of Dialkyl 1-Aryl-1-hydroxymethylphosphonates to Benzyl Phosphates

2020 ◽  
Vol 24 (4) ◽  
pp. 465-471 ◽  
Author(s):  
Zita Rádai ◽  
Réka Szabó ◽  
Áron Szigetvári ◽  
Nóra Zsuzsa Kiss ◽  
Zoltán Mucsi ◽  
...  
Keyword(s):  
Quantum Chemical ◽  
Room Temperature ◽  
Phase Transfer ◽  
One Pot ◽  
Substrate Dependence ◽  
Triethylbenzylammonium Chloride ◽  
One Step ◽  
The Pudovik Reaction ◽  
The One ◽  
Solid Liquid

The phospha-Brook rearrangement of dialkyl 1-aryl-1-hydroxymethylphosphonates (HPs) to the corresponding benzyl phosphates (BPs) has been elaborated under solid-liquid phase transfer catalytic conditions. The best procedure involved the use of triethylbenzylammonium chloride as the catalyst and Cs2CO3 as the base in acetonitrile as the solvent at room temperature. The substrate dependence of the rearrangement has been studied, and the mechanism of the transformation under discussion was explored by quantum chemical calculations. The key intermediate is an oxaphosphirane. The one-pot version starting with the Pudovik reaction has also been developed. The conditions of this tandem transformation were the same, as those for the one-step HP→BP conversion.

scholarly journals Modes of Interaction in Naturally Occurring Medical Encounters With General Practitioners: The “One in a Million” Study

2021 ◽  
pp. 104973232199379
Author(s):  
Olaug S. Lian ◽  
Sarah Nettleton ◽  
Åge Wifstad ◽  
Christopher Dowrick
Keyword(s):  
General Practitioners ◽  
Narrative Analysis ◽  
Mode Competition ◽  
General Applicability ◽  
Naturally Occurring ◽  
Wide Range ◽  
The One ◽  
Narrative Mode ◽  
Modes Of Interaction

In this article, we qualitatively explore the manner and style in which medical encounters between patients and general practitioners (GPs) are mutually conducted, as exhibited in situ in 10 consultations sourced from the One in a Million: Primary Care Consultations Archive in England. Our main objectives are to identify interactional modes, to develop a classification of these modes, and to uncover how modes emerge and shift both within and between consultations. Deploying an interactional perspective and a thematic and narrative analysis of consultation transcripts, we identified five distinctive interactional modes: question and answer (Q&A) mode, lecture mode, probabilistic mode, competition mode, and narrative mode. Most modes are GP-led. Mode shifts within consultations generally map on to the chronology of the medical encounter. Patient-led narrative modes are initiated by patients themselves, which demonstrates agency. Our classification of modes derives from complete naturally occurring consultations, covering a wide range of symptoms, and may have general applicability.

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