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Unraveling Entropic Rate Acceleration Induced by Solvent Dynamics in Membrane Enzymes
Published on: January 16, 2016
A role for flexible loops in enzyme catalysis.
M Merced Malabanan1, Tina L Amyes, John P Richard
1Department of Chemistry, University at Buffalo, SUNY, Buffalo, NY 14260-3000, USA.
Current Opinion in Structural Biology
|October 19, 2010
Summary
Enzymes like triosephosphate isomerase (TIM) use a flexible loop to bind substrates, enhancing catalytic activity. Loop closure expels water, increasing binding energy and stabilizing transition states for reactions like proton and hydride transfer.
Area of Science:
- Biochemistry
- Enzyme kinetics
- Structural biology
Background:
- Enzymes utilize binding energy to stabilize transition states.
- Flexible loops in enzyme active sites play a crucial role in catalysis.
- Water exclusion from active sites can significantly impact reaction rates.
Purpose of the Study:
- To investigate the role of a flexible phosphate gripper loop in enzyme catalysis.
- To understand how substrate binding and conformational changes affect enzyme activity.
- To elucidate the mechanisms of proton transfer, hydride transfer, and decarboxylation in specific enzymes.
Main Methods:
- Comparative analysis of enzyme structures and functions.
- Kinetic studies of enzyme-catalyzed reactions.
- Computational modeling of enzyme-substrate interactions and conformational changes.
Main Results:
- The phosphate gripper loop binds phosphite dianion, activating truncated substrates.
- Loop closure in triosephosphate isomerase (TIM) excludes water from the active site.
- This water exclusion lowers dielectric constant, enhancing electrostatic stabilization and increasing the basicity of active site glutamate.
Conclusions:
- Enzyme active site water exclusion is a key mechanism for transition state stabilization.
- Conformational changes, including loop closure, optimize enzyme active site environments for catalysis.
- Specific interactions, like the 'hydrophobic cage', fine-tune catalytic residues for efficient reactions.
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