Single Enzyme Is Necessary for Development of Diabetes

2014 ◽  
Vol 9 (9) ◽  
pp. 359-359
Keyword(s):  
2018 ◽  
Author(s):  
Justin Eilertsen ◽  
Santiago Schnell

<div>As a case study, we consider a coupled enzyme assay of sequential enzyme reactions obeying the Michaelis--Menten reaction mechanism. The sequential reaction consists of a single-substrate, single-enzyme non-observable reaction followed by another single-substrate, single-enzyme observable reaction (indicator reaction). In this assay, the product of the non-observable reaction becomes the substrate of the indicator reaction. A mathematical analysis of the reaction kinetics is performed, and it is found that after an initial fast transient, the sequential reaction is described by a pair of interacting Michaelis--Menten equations. Timescales that approximate the respective lengths of the indicator and non-observable reactions, as well as conditions for the validity of the Michaelis--Menten equations are derived. The theory can be extended to deal with more complex sequences of enzyme catalyzed reactions.</div>


2018 ◽  
Author(s):  
Justin Eilertsen ◽  
Santiago Schnell

<div>As a case study, we consider a coupled enzyme assay of sequential enzyme reactions obeying the Michaelis-Menten reaction mechanism. The sequential reaction consists of a single-substrate, single enzyme non-observable reaction followed by another single-substrate, single enzyme observable reaction (indicator reaction). In this assay, the product of the non-observable reaction becomes the substrate of the indicator reaction. A mathematical analysis of the reaction kinetics is performed, and it is found that after an initial fast transient, the sequential reaction is described by a pair of interacting Michaelis-Menten equations. Timescales that approximate the respective lengths of the indicator and non-observable reactions, as well as conditions for the validity of the Michaelis-Menten equations are derived. The theory can be extended to deal with more complex sequences of enzyme catalyzed reactions.</div>


Author(s):  
Sung Oh Woo ◽  
Myungkeun Oh ◽  
Lina Alhalhooly ◽  
Jasmin Farmakes ◽  
Arith J. Rajapakse ◽  
...  

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Carlos G. Acevedo-Rocha ◽  
Aitao Li ◽  
Lorenzo D’Amore ◽  
Sabrina Hoebenreich ◽  
Joaquin Sanchis ◽  
...  

AbstractMultidimensional fitness landscapes provide insights into the molecular basis of laboratory and natural evolution. To date, such efforts usually focus on limited protein families and a single enzyme trait, with little concern about the relationship between protein epistasis and conformational dynamics. Here, we report a multiparametric fitness landscape for a cytochrome P450 monooxygenase that was engineered for the regio- and stereoselective hydroxylation of a steroid. We develop a computational program to automatically quantify non-additive effects among all possible mutational pathways, finding pervasive cooperative signs and magnitude epistasis on multiple catalytic traits. By using quantum mechanics and molecular dynamics simulations, we show that these effects are modulated by long-range interactions in loops, helices and β-strands that gate the substrate access channel allowing for optimal catalysis. Our work highlights the importance of conformational dynamics on epistasis in an enzyme involved in secondary metabolism and offers insights for engineering P450s.


2020 ◽  
Vol 40 (04) ◽  
pp. 524-535
Author(s):  
Dmitry Y. Nechipurenko ◽  
Aleksey M. Shibeko ◽  
Anastasia N. Sveshnikova ◽  
Mikhail A. Panteleev

AbstractComputational physiology, i.e., reproduction of physiological (and, by extension, pathophysiological) processes in silico, could be considered one of the major goals in computational biology. One might use computers to simulate molecular interactions, enzyme kinetics, gene expression, or whole networks of biochemical reactions, but it is (patho)physiological meaning that is usually the meaningful goal of the research even when a single enzyme is its subject. Although exponential rise in the use of computational and mathematical models in the field of hemostasis and thrombosis began in the 1980s (first for blood coagulation, then for platelet adhesion, and finally for platelet signal transduction), the majority of their successful applications are still focused on simulating the elements of the hemostatic system rather than the total (patho)physiological response in situ. Here we discuss the state of the art, the state of the progress toward the efficient “virtual thrombus formation,” and what one can already get from the existing models.


2020 ◽  
Vol 53 (13) ◽  
pp. 5487-5496
Author(s):  
Yiping Wang ◽  
Yen Theng Cheng ◽  
Cheng Cao ◽  
James D. Oliver ◽  
Martina H. Stenzel ◽  
...  

2006 ◽  
Vol 3 (3) ◽  
pp. 158-158
Author(s):  
Allison Doerr

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