Effect of Metal Cofactors on the Reaction Velocity

Author(s):  
Stephen A. Kuby
Science ◽  
2021 ◽  
pp. eabi5224
Author(s):  
Nunziata Maio ◽  
Bernard A. P. Lafont ◽  
Debangsu Sil ◽  
Yan Li ◽  
J. Martin Bollinger ◽  
...  

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causal agent of coronavirus disease 2019 (COVID-19), uses an RNA-dependent RNA polymerase (RdRp) for the replication of its genome and the transcription of its genes. We found that the catalytic subunit of the RdRp, nsp12, ligates two iron-sulfur metal cofactors in sites that were modeled as zinc centers in the available cryo-electron microscopy structures of the RdRp complex. These metal binding sites are essential for replication and for interaction with the viral helicase. Oxidation of the clusters by the stable nitroxide TEMPOL caused their disassembly, potently inhibited the RdRp, and blocked SARS-CoV-2 replication in cell culture. These iron-sulfur clusters thus serve as cofactors for the SARS-CoV-2 RdRp and are targets for therapy of COVID-19.


2014 ◽  
Vol 137 (1) ◽  
pp. 390-398 ◽  
Author(s):  
James N. Vranish ◽  
William K. Russell ◽  
Lusa E. Yu ◽  
Rachael M. Cox ◽  
David H. Russell ◽  
...  

1981 ◽  
Vol 197 (2) ◽  
pp. 523-526 ◽  
Author(s):  
Paul D. Wightman ◽  
Mary Ellen Dahlgren ◽  
James C. Hall ◽  
Philip Davies ◽  
Robert J. Bonney

Resident mouse peritoneal macrophages contain a phospholipase C of high activity that is specific for phosphatidylinositol. The activity has a neutral pH optimum, is Ca2+-dependent and has a maximum reaction velocity of 525nmol/h per mg of protein. Certain phenothiazines are potent inhibitors of this activity.


1937 ◽  
Vol 15b (6) ◽  
pp. 247-253 ◽  
Author(s):  
C. C. Coffin ◽  
J. R. Dacey ◽  
N. A. D. Parlee

Ethylidene dibutyrate and heptylidene diacetate decompose in the vapor state at temperatures between 200° and 300 °C. to form an aldehyde and an anhydride. The reactions are homogeneous, unimolecular, and complete. The activation energy is the same as that previously found for other members of this homologous series. Ethylidene dibutyrate decomposes at the same rate as ethylidene diacetate, and thus provides further evidence that the specific reaction velocity is independent of the size of the anhydride radicals. Heptylidene diacetate decomposes at the same rate as butylidene diacetate. This indicates that after the aldehyde radical has attained a certain size (three or four carbon atoms) the addition of –CH2− groups leaves the specific reaction velocity unchanged. The velocity constants are given by the equations[Formula: see text]


2018 ◽  
Vol 4 (3-4) ◽  
pp. 198-207 ◽  
Author(s):  
Sónia Chan ◽  
Sérgio Ferreira ◽  
Bruno Ramos ◽  
Maria João Santos ◽  
Luís Carlos Matos ◽  
...  

Background/Aims: Acupuncture and moxibustion, when used together, have act mechanically and thermally on treated reflexological areas. The main goal of this work was to evaluate the effects of acupuncture and moxibustion on the electrophysiological properties of the ulnar nerve. Methods: Electrical stimulation was applied to the ulnar nerve above the epi­condyle of 28 volunteers. A 20-V potential was applied, and after each 10 impulses it was increased by 10 V, up to a maximum of 80 V. At 20 and 80 V, the participants were asked to rate the discomfort from 0 to 10 on a Numeric Rating Scale for pain. After the first stimulation and data collection, the control group rested for 6 min, while the intervention group was submitted to acupuncture and moxibustion on Lingdao (HT 4). Following this period of time, a second electrical stimulation was performed on both groups. Results: The discomfort was greater in the intervention group during the second stimulation. The stimulus required to achieve the maximum amplitude decreased, but the changes were only statistically significant in the intervention group (p = 0.006). An increase in latency and a decrease in reaction velocity were noticed between the first and the second stimulation for both groups; however, only the control group presented statistically significant differences (p = 0.018 and p = 0.022, respectively). Conclusions: Acupuncture and moxibustion on HT 4 increased the electrical sensitivity, decreased the stimulus intensity to achieve the maximum amplitude, and avoided a significant increase in latency and decrease in reaction velocity in two consecutive electrical stimulations.


The relation between reaction rate and potential (or time) for electrochemical surface processes occurring under potentiodynamic control (linear potential-time programme) has been investigated with particular reference to the behaviour of thin surface oxide films on noble metals. The kinetics of processes involving adsorbed electroactive species are treated for several model cases; the rate equations are developed for mechanisms involving various reaction orders or for processes involving adsorbed reactant interactions and surface heterogeneity effects. By examination of the dependence of the reaction rate (current) with time and the effect of potential scan rate, v , on the maximum reaction velocity and the potential at which it occurs, the models may be distinguished. In this manner, the inter­dependence of v and the reaction velocity constants k a and k c for the anodic oxidation and the cathodic reduction processes respectively, can be quantitatively established. The relation between quasi-equilibrium situations where the reverse reaction is significant and irreversible situations where it is not can be demonstrated. Heterogeneity terms introduced into the kinetic relations express deviations from Langmuir adsorption behaviour and may be an intrinsic property of the substrate surface or a property of the adsorbed reactant (induced heterogeneity). Applications of the treatment are made to reduction of surface oxide species at the noble metals and the significance of hysteresis and time effects in the processes of electrochemical formation and reduction of surface oxide at platinum, rhodium, iridium and palladium is investigated.


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