ArticleACS catalysis2015
Protein Conformational Landscapes and Catalysis. Influence of Active Site Conformations in the Reaction Catalyzed by L-Lactate Dehydrogenase.
Article in ACS catalysis, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed.
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- Prognostic Factors Analysis in Patients with Hepatocellular Carcinoma Receiving PD-1/PD-L1 Inhibitors.Journal of hepatocellular carcinoma · 2026Article
- Metal coordination and enzymatic reaction of the glioma-target R132H isocitrate dehydrogenase 1: Insights by molecular simulations.PloS one · 2025Article
- Electrostatic Preorganization in Three Distinct Heterogeneous Proteasome β-Subunits.ACS catalysis · 2024Article
- Cooperative Conformational Transitions Underpin the Activation Heat Capacity in the Temperature Dependence of Enzyme Catalysis.ACS catalysis · 2024Article
- Decrypting Allostery in Membrane-Bound K-Ras4B Using ComplementaryJournal of the American Chemical Society · 2024Article
- Structure, Mutagenesis, and QM:MM Modeling of 3-Ketosteroid ΔBiochemistry · 2023Article
- Revisiting the Warburg Effect with Focus on Lactate.Cancers · 2022Review
- Covalent Inhibition of thePharmaceuticals (Basel, Switzerland) · 2022Article
- Natural products targeting human lactate dehydrogenases for cancer therapy: A mini review.Frontiers in chemistry · 2022Review
- Transfer hydrogenations catalyzed by streptavidin-hosted secondary amine organocatalysts.Chemical communications (Cambridge, England) · 2021Article
- High Pretreatment LDH Predicts Poor Prognosis in Hypopharyngeal Cancer.Frontiers in oncology · 2021Article
- Pressure tolerance of deep-sea enzymes can be evolved through increasing volume changes in protein transitions: a study with lactate dehydrogenases from abyssal and hadal fishes.The FEBS journal · 2020Article
- Mechanism of inhibition of SARS-CoV-2 MChemical science · 2020Article
- Enhancing aChemical science · 2020Article
- Loss of Hyperconjugative Effects Drives Hydride Transfer during Dihydrofolate Reductase Catalysis.ACS catalysis · 2019Article
- Convergence of theory and experiment on the role of preorganization, quantum tunneling and enzyme motions into flavoenzyme-catalyzed hydride transfer.ACS catalysis · 2019Article
- Roles of Closed- and Open-Loop Conformations in Large-Scale Structural Transitions of l-Lactate Dehydrogenase.ACS omega · 2019Article
- Experimental and Computational Studies Delineate the Role of Asparagine 177 in Hydride Transfer for E. coli Thymidylate Synthase.ACS catalysis · 2018Article
- Promoting Vibrations and the Function of Enzymes. Emerging Theoretical and Experimental Convergence.Biochemistry · 2018Review
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Authors and funding
4 authors.
Funding
Abstract
In the last decade L-Lactate Dehydrogenase (LDH) has become an extremely useful marker in both clinical diagnosis and in monitoring the course of many human diseases. It has been assumed from the 80s that the full catalytic process of LDH starts with the binding of the cofactor and the substrate followed by the enclosure of the active site by a mobile loop of the protein before the reaction to take place. In this paper we show that the chemical step of the LDH catalyzed reaction can proceed within the open loop conformation, and the different reactivity of the different protein conformations would be in agreement with the broad range of rate constants measured in single molecule spectrometry studies. Starting from a recently solved X-ray diffraction structure that presented an open loop conformation in two of the four chains of the tetramer, QM/MM free energy surfaces have been obtained at different levels of theory. Depending on the level of theory used to describe the electronic structure, the free energy barrier for the transformation of pyruvate into lactate with the open conformation of the protein varies between 12.9 and 16.3 kcal/mol, after quantizing the vibrations and adding the contributions of recrossing and tunneling effects. These values are very close to the experimentally deduced one (14.2 kcal·mol
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