An introduction to enzyme structure dynamics and enzyme catalysis

Author(s):  
Jitesh Kumar ◽  
Ashok Pandey ◽  
Sudhir P. Singh
2019 ◽  
Author(s):  
Medhanjali Dasgupta ◽  
Dominik Budday ◽  
Saulo H.P. de Oliveira ◽  
Peter Madzelan ◽  
Darya Marchany-Rivera ◽  
...  

Summary ParagraphProtein dynamics play an important role in enzyme catalysis1-4. Many enzymes form covalent catalytic intermediates that can alter enzyme structure and conformational dynamics5,6. How these changes in enzyme structure and dynamics facilitate passage along the reaction coordinate is a fundamental unanswered question in structural enzymology. Here, we use Mix-and-Inject Serial Femtosecond X-ray Crystallography (MISC) at an X-ray Free Electron Laser (XFEL)7-10, ambient temperature X-ray crystallography, computer simulations, and enzyme kinetics to characterize how covalent modification of the active site cysteine residue in isocyanide hydratase (ICH) alters the enzyme’s conformational ensemble throughout the catalytic cycle. With MISC, we directly observe formation of a thioimidate covalent intermediate during ICH catalysis. The intermediate exhibits changes in the active site electrostatic environment, disrupting a hydrogen bond and triggering a cascade of conformational changes in ICH. X-ray-induced formation of a cysteine-sulfenic acid at the catalytic nucleophile (Cys101-SOH) with conventional crystallography at ambient temperature induces similar conformational shifts, demonstrating that these enzyme motions result from cysteine modification. Computer simulations show how cysteine modification-gated structural changes allosterically propagate through the ICH dimer. Mutations at Gly150 that modulate helical mobility reduce ICH catalytic turnover and alter its pre-steady state kinetic behavior, establishing that helical mobility is important for ICH catalytic efficiency. Taken together, our results demonstrate the potential of mix-and-inject XFEL crystallography to capture otherwise elusive mechanistic details of enzyme catalysis and dynamics from microcrystalline samples7,11. This approach can connect conformational dynamics to function for the large class of systems that rely on covalently modified cysteine residues for catalysis or regulation, resolving long-standing questions about enzyme mechanism and functionally relevant non-equilibrium enzyme motions.


2010 ◽  
Vol 11 (S6) ◽  
Author(s):  
Ugur Uzuner ◽  
Weibing Shi ◽  
Lantao Liu ◽  
Sanmin Liu ◽  
Susie Y Dai ◽  
...  

2020 ◽  
Vol 15 (2) ◽  
pp. 68
Author(s):  
А. Н. Сухов

This given article reveals the topicality not only of destructive, but also of constructive, as well as hybrid conflicts. Practically it has been done for the first time. It also describes the history of the formation of both foreign and domestic social conflictology. At the same time, the chronology of the development of the latter is restored and presented objectively, in full, taking into account the contribution of those researchers who actually stood at its origins. The article deals with the essence of the socio-psychological approach to understanding conflicts. The subject of social conflictology includes the regularities of their occurrence and manifestation at various levels, spheres and conditions, including normal, complicated and extreme ones. Social conflictology includes the theory and practice of diagnosing, resolving, and resolving social conflicts. It analyzes the difficulties that occur in defining the concept, structure, dynamics, and classification of social conflicts. Therefore, it is no accident that the most important task is to create a full-fledged theory of social conflicts. Without this, it is impossible to talk about effective settlement and resolution of social conflicts. Social conflictology is an integral part of conflictology. There is still a lot of work to be done, both in theory and in application, for its complete design. At present, there is an urgent need to develop conflict-related competence not only of professionals, but also for various groups of the population.


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