Related Experiment Video
Updated: Jul 24, 2025
09:42
Unraveling Entropic Rate Acceleration Induced by Solvent Dynamics in Membrane Enzymes
Published on: January 16, 2016
9.1K
Resolving conformational changes that mediate a two-step catalytic mechanism in a model enzyme.
Jack B Greisman1, Kevin M Dalton1, Dennis E Brookner1
1Department of Molecular & Cellular Biology, Harvard University, Cambridge, MA, United States.
Biorxiv : the Preprint Server for Biology
|July 3, 2023
Summary
Enzymes like dihydrofolate reductase (DHFR) use conformational dynamics to speed up reactions. This study reveals how DHFR
Area of Science:
- Biochemistry
- Structural Biology
- Enzymology
Background:
- Enzymes accelerate biochemical reactions by precisely organizing substrates and amino acids.
- Understanding the role of protein conformational dynamics in enzyme catalysis is limited by experimental challenges.
- The exact mechanisms by which E. coli dihydrofolate reductase (DHFR) regulates its active site for proton and hydride transfer are unknown.
Approach:
- Utilized X-ray diffraction experiments with ligand, temperature, and electric field perturbations.
- Identified coupled conformational changes within DHFR.
- Mapped structural rearrangements and their relation to substrate protonation.
Key Points:
- A global hinge motion and local structural networks were identified in DHFR.
- Substrate protonation engages these dynamic elements to control solvent access.
- These dynamics are crucial for efficient catalysis in DHFR.
Conclusions:
- DHFR employs a dynamic free energy landscape to guide its two-step catalytic mechanism.
- The enzyme's catalytic efficiency is responsive to the substrate's protonation state.
- Conformational dynamics play a critical role in regulating enzyme active site environments and catalysis.
Related Concept Videos
01:13Introduction to Mechanisms of Enzyme Catalysis
8.3K
For many years, scientists thought that enzyme-substrate binding took place in a simple "lock-and-key" fashion. This model stated that the enzyme and substrate fit together perfectly in one instantaneous step. However, current research supports a more refined view scientists call induced fit. The induced-fit model expands upon the lock-and-key model by describing a more dynamic interaction between enzyme and substrate. As the enzyme and substrate come together, their interaction causes...
8.3K
01:13Induced-fit Model
81.2K
Most chemical reactions in cells require enzymes—biological catalysts that speed up the reaction without being consumed or permanently changed. They reduce the activation energy needed to convert the reactants into products. Enzymes are proteins, that usually work by binding to a substrate—a reactant molecule that they act upon.
Enzymes exhibit substrate specificity, meaning that they can only bind to certain substrates. This is mainly determined by the shape and chemical...
Enzymes exhibit substrate specificity, meaning that they can only bind to certain substrates. This is mainly determined by the shape and chemical...
81.2K
01:58Cooperative Allosteric Transitions
7.9K
Cooperative allosteric transitions can occur in multimeric proteins, where each subunit of the protein has its own ligand-binding site. When a ligand binds to any of these subunits, it triggers a conformational change that affects the binding sites in the other subunits; this can change the affinity of the other sites for their respective ligands. The ability of the protein to change the shape of its binding site is attributed to the presence of a mix of flexible and stable segments in the...
7.9K
02:34Enzymes
82.0K
Inside living organisms, enzymes act as catalysts for many biochemical reactions involved in cellular metabolism. The role of enzymes is to reduce the activation energies of biochemical reactions by forming complexes with its substrates. The lowering of activation energies favor an increase in the rates of biochemical reactions.
Enzyme deficiencies can often translate into life-threatening diseases. For example, a genetic abnormality resulting in the deficiency of the enzyme G6PD...
Enzyme deficiencies can often translate into life-threatening diseases. For example, a genetic abnormality resulting in the deficiency of the enzyme G6PD...
82.0K
01:48ATP Synthase: Mechanism
14.8K
In animals, the mitochondrial F1F0 ATP synthase is the key protein that synthesizes ATP molecules through a complex catalytic mechanism. While the nuclear genome encodes the majority of ATP synthase subunits, the mitochondrial genome encodes some of the enzyme's most critical components. The formation of this multi-subunit enzyme is a complex multi-step process regulated at the level of transcription, translation, and assembly. Defects in one or more of these steps can result in decreased...
14.8K
02:50Catalysis
27.1K
The presence of a catalyst affects the rate of a chemical reaction. A catalyst is a substance that can increase the reaction rate without being consumed during the process. A basic comprehension of a catalysts’ role during chemical reactions can be understood from the concept of reaction mechanisms and energy diagrams.
27.1K