التفاصيل البيبلوغرافية
| العنوان: |
Free Energy Surface of the Michaelis Complex of LactateDehydrogenase: A Network Analysis of Microsecond Simulations. |
| المؤلفون: |
Xiaoliang Pan1, Steven D. Schwartz1 |
| المصدر: |
Journal of Physical Chemistry B. Apr2015, Vol. 119 Issue 17, p5430-5436. 7p. |
| مصطلحات موضوعية: |
*FREE energy (Thermodynamics), *LACTATE dehydrogenase, *COMPUTER simulation, *PROTEIN structure, *MOLECULAR recognition, *PROTEIN conformation |
| مستخلص: |
It has long been recognized thatthe structure of a protein createsa hierarchy of conformations interconverting on multiple time scales.The conformational heterogeneity of the Michaelis complex is of particularinterest in the context of enzymatic catalysis in which the reactantis usually represented by a single conformation of the enzyme/substratecomplex. Lactate dehydrogenase (LDH) catalyzes the interconversionof pyruvate and lactate with concomitant interconversion of two formsof the cofactor nicotinamide adenine dinucleotide (NADH and NAD+). Recent experimental results suggest that multiple substatesexist within the Michaelis complex of LDH, and they show a strongvariance in their propensity toward the on-enzyme chemical step. Inthis study, microsecond-scale all-atom molecular dynamics simulationswere performed on LDH to explore the free energy landscape of theMichaelis complex, and network analysis was used to characterize thedistribution of the conformations. Our results provide a detailedview of the kinetic network of the Michaelis complex and the structuresof the substates at atomistic scales. They also shed light on thecomplete picture of the catalytic mechanism of LDH. [ABSTRACT FROM AUTHOR] |
| قاعدة البيانات: |
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