Roles of Closed- and Open-Loop Conformations in Large-Scale Structural Transitions of l‑Lactate Dehydrogenase
| العنوان: | Roles of Closed- and Open-Loop Conformations in Large-Scale Structural Transitions of l‑Lactate Dehydrogenase |
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| المؤلفون: | Kimichi Suzuki, Satoshi Maeda, Keiji Morokuma |
| المصدر: | ACS Omega, Vol 4, Iss 1, Pp 1178-1184 (2019) ACS Omega |
| بيانات النشر: | American Chemical Society, 2019. |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | Quantitative Biology::Biomolecules, Chemistry, General Chemical Engineering, Substrate (chemistry), L-Lactate dehydrogenase, Dehydrogenase, General Chemistry, Energy minimization, Molecular mechanics, Chemical reaction, Article, Quantitative Biology::Subcellular Processes, lcsh:Chemistry, Crystallography, lcsh:QD1-999, Structural transition, Reaction path |
| الوصف: | The mechanism of l-lactate generation from pyruvate by l-lactate dehydrogenase (LDH) from the rabbit muscle was studied theoretically by the multistructural microiteration (MSM) method combined with the quantum mechanics/molecular mechanics (QM/MM)–ONIOM method, where the MSM method describes the MM environment as a weighted average of multiple different structures that are fully relaxed during geometry optimization or a reaction path calculation for the QM part. The results showed that the substrate binding and product states were stabilized only in the open-loop conformation of LDH and the reaction occurred in the closed-loop conformation. In other words, before and after the chemical reaction, a large-scale structural transition from the open-loop conformation to the closed-loop conformation and vice versa occurred. The closed-loop conformation stabilized the transition state of the reaction. In contrast, the open-loop conformation stabilized the substrate binding and final states. In other words, the closed- to open-loop transition at the substrate binding state urges capture of the substrate molecule, the subsequent open- to closed-loop transition promotes the product generation, and the final closed- to open-loop transition at the final state prevents the reverse reaction going back to the substrate binding state. It is thus suggested that the exchange of stability between the closed- and open-loop conformations at different states promotes the catalytic cycle. |
| اللغة: | English |
| تدمد: | 2470-1343 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::a931a9d51514e60a2993faaf6943f2a9Test https://doaj.org/article/3bf1283163c3417a9f153ff53d025f1dTest |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....a931a9d51514e60a2993faaf6943f2a9 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 24701343 |
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