ArticleThe journal of physical chemistry. B2014
Direct evidence of catalytic heterogeneity in lactate dehydrogenase by temperature jump infrared spectroscopy.
Article in The journal of physical chemistry. B, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
23 citing papers in PubMed.
- Allostery and Evolution: A Molecular Journey Through the Structural and Dynamical Landscape of an Enzyme Super Family.Molecular biology and evolution · 2025Article
- High throughput and quantitative enzymology in the genomic era.Current opinion in structural biology · 2021Review
- Acceleration of catalysis in dihydrofolate reductase by transient, site-specific photothermal excitation.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Effect of Protein Isotope Labeling on the Catalytic Mechanism of Lactate Dehydrogenase.The journal of physical chemistry. B · 2019Article
- Active-Site Glu165 Activation in Triosephosphate Isomerase and Its Deprotonation Kinetics.The journal of physical chemistry. B · 2019Article
- Article
- Small molecule cores demonstrate non-competitive inhibition of lactate dehydrogenase.MedChemComm · 2018Article
- Activity-Related Microsecond Dynamics Revealed by Temperature-Jump Förster Resonance Energy Transfer Measurements on Thermophilic Alcohol Dehydrogenase.Journal of the American Chemical Society · 2018Article
- Difference FTIR Studies of Substrate Distribution in Triosephosphate Isomerase.The journal of physical chemistry. B · 2017Article
- Trigger loop dynamics can explain stimulation of intrinsic termination by bacterial RNA polymerase without terminator hairpin contact.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
- Mechanistic Analysis of Fluorescence Quenching of Reduced Nicotinamide Adenine Dinucleotide by Oxamate in Lactate Dehydrogenase Ternary Complexes.Photochemistry and photobiology · 2017Article
- Thermodynamic and Structural Adaptation Differences between the Mesophilic and Psychrophilic Lactate Dehydrogenases.Biochemistry · 2017Article
- Electric Fields and Enzyme Catalysis.Annual review of biochemistry · 2017Review
- Resolution of Submillisecond Kinetics of Multiple Reaction Pathways for Lactate Dehydrogenase.Biophysical journal · 2017Article
- Triple Isotope Effects Support Concerted Hydride and Proton Transfer and Promoting Vibrations in Human Heart Lactate Dehydrogenase.Journal of the American Chemical Society · 2016Article
- Conformational Heterogeneity in the Michaelis Complex of Lactate Dehydrogenase: An Analysis of Vibrational Spectroscopy Using Markov and Hidden Markov Models.The journal of physical chemistry. B · 2016Article
- Active-Loop Dynamics within the Michaelis Complex of Lactate Dehydrogenase from Bacillus stearothermophilus.Biochemistry · 2016Article
- Ligand-Dependent Conformational Dynamics of Dihydrofolate Reductase.Biochemistry · 2016Article
- The influence of active site conformations on the hydride transfer step of the thymidylate synthase reaction mechanism.Physical chemistry chemical physics : PCCP · 2015Article
- Mechanism of Thermal Adaptation in the Lactate Dehydrogenases.The journal of physical chemistry. B · 2015Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors.
Funding
Abstract
Protein conformational heterogeneity and dynamics are known to play an important role in enzyme catalysis, but their influence has been difficult to observe directly. We have studied the effects of heterogeneity in the catalytic reaction of pig heart lactate dehydrogenase using isotope edited infrared spectroscopy, laser-induced temperature jump relaxation, and kinetic modeling. The isotope edited infrared spectrum reveals the presence of multiple reactive conformations of pyruvate bound to the enzyme, with three major reactive populations having substrate C2 carbonyl stretches at 1686, 1679, and 1674 cm(-1), respectively. The temperature jump relaxation measurements and kinetic modeling indicate that these substates form a heterogeneous branched reaction pathway, and each substate catalyzes the conversion of pyruvate to lactate with a different rate. Furthermore, the rate of hydride transfer is inversely correlated with the frequency of the C2 carbonyl stretch (the rate increases as the frequency decreases), consistent with the relationship between the frequency of this mode and the polarization of the bond, which determines its reactivity toward hydride transfer. The enzyme does not appear to be optimized to use the fastest pathway preferentially but rather accesses multiple pathways in a search process that often selects slower ones. These results provide further support for a dynamic view of enzyme catalysis where the role of the enzyme is not just to bring reactants together but also to guide the conformational search for chemically competent interactions.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.