Free Energy Surface of the Michaelis Complex of Lactate Dehydrogenase: A Network Analysis of Microsecond Simulations
| العنوان: | Free Energy Surface of the Michaelis Complex of Lactate Dehydrogenase: A Network Analysis of Microsecond Simulations |
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| المؤلفون: | Xiaoliang Pan, Steven D. Schwartz |
| المصدر: | The Journal of Physical Chemistry B. 119:5430-5436 |
| بيانات النشر: | American Chemical Society (ACS), 2015. |
| سنة النشر: | 2015 |
| مصطلحات موضوعية: | Time Factors, Protein Conformation, Stereochemistry, Lactate dehydrogenase A, Context (language use), Molecular Dynamics Simulation, Nicotinamide adenine dinucleotide, Article, Cofactor, Enzyme catalysis, chemistry.chemical_compound, Lactate dehydrogenase, Pyruvic Acid, Materials Chemistry, Physical and Theoretical Chemistry, education, education.field_of_study, L-Lactate Dehydrogenase, biology, Energy landscape, NAD, Surfaces, Coatings and Films, Kinetics, chemistry, Biocatalysis, biology.protein, Thermodynamics, NAD+ kinase |
| الوصف: | It has long been recognized that the structure of a protein creates a hierarchy of conformations interconverting on multiple time scales. The conformational heterogeneity of the Michaelis complex is of particular interest in the context of enzymatic catalysis in which the reactant is usually represented by a single conformation of the enzyme/substrate complex. Lactate dehydrogenase (LDH) catalyzes the interconversion of pyruvate and lactate with concomitant interconversion of two forms of the cofactor nicotinamide adenine dinucleotide (NADH and NAD(+)). Recent experimental results suggest that multiple substates exist within the Michaelis complex of LDH, and they show a strong variance in their propensity toward the on-enzyme chemical step. In this study, microsecond-scale all-atom molecular dynamics simulations were performed on LDH to explore the free energy landscape of the Michaelis complex, and network analysis was used to characterize the distribution of the conformations. Our results provide a detailed view of the kinetic network of the Michaelis complex and the structures of the substates at atomistic scales. They also shed light on the complete picture of the catalytic mechanism of LDH. |
| تدمد: | 1520-5207 1520-6106 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::31be199ee1172943106ef71573bc4473Test https://doi.org/10.1021/acs.jpcb.5b01840Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....31be199ee1172943106ef71573bc4473 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15205207 15206106 |
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