دورية أكاديمية
Dissecting the Allosteric Fine-Tuning of Enzyme Catalysis
| العنوان: | Dissecting the Allosteric Fine-Tuning of Enzyme Catalysis |
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| المؤلفون: | Xin-Qiu Yao, Donald Hamelberg |
| سنة النشر: | 2024 |
| مصطلحات موضوعية: | Biophysics, Genetics, Developmental Biology, Infectious Diseases, Computational Biology, Biological Sciences not elsewhere classified, Chemical Sciences not elsewhere classified, Physical Sciences not elsewhere classified, using human pin1, potential dynamic basis, combined effect determines, biomolecules requires separating, advanced statistical technique, final allosteric output, allosteric modulation using, catalyzed reaction rate, related conformational dynamics, allosteric systems, allosteric regulation, allosteric effector, reaction kinetics, reaction dynamics, reaction coordinate, various enzyme, prospective applications, pharmaceutical sciences, modulated allosterically, microscopic description, methods developed, largely missing |
| الوصف: | Fully understanding the mechanism of allosteric regulation in biomolecules requires separating and examining all of the involved factors. In enzyme catalysis, allosteric effector binding shifts the structure and dynamics of the active site, leading to modified energetic (e.g., energy barrier) and dynamical (e.g., diffusion coefficient) factors underlying the catalyzed reaction rate. Such modifications can be subtle and dependent on the type of allosteric effector, representing a fine-tuning of protein function. The microscopic description of allosteric regulation at the level of function-dictating factors has prospective applications in fundamental and pharmaceutical sciences, which is, however, largely missing so far. Here, we characterize the allosteric fine-tuning of enzyme catalysis, using human Pin1 as an example, by performing more than half-millisecond all-atom molecular dynamics simulations. Changes of reaction kinetics and the dictating factors, including the free energy surface along the reaction coordinate and the diffusion coefficient of the reaction dynamics, under various enzyme and allosteric effector binding conditions are examined. Our results suggest equal importance of the energetic and dynamical factors, both of which can be modulated allosterically, and the combined effect determines the final allosteric output. We also reveal the potential dynamic basis for allosteric modulation using an advanced statistical technique to detect function-related conformational dynamics. Methods developed in this work can be applied to other allosteric systems. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | unknown |
| العلاقة: | https://figshare.com/articles/journal_contribution/Dissecting_the_Allosteric_Fine-Tuning_of_Enzyme_Catalysis/25150813Test |
| DOI: | 10.1021/jacsau.3c00806.s001 |
| الإتاحة: | https://doi.org/10.1021/jacsau.3c00806.s001Test https://figshare.com/articles/journal_contribution/Dissecting_the_Allosteric_Fine-Tuning_of_Enzyme_Catalysis/25150813Test |
| حقوق: | CC BY-NC 4.0 |
| رقم الانضمام: | edsbas.5740E3D6 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1021/jacsau.3c00806.s001 |
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