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Updated: Aug 8, 2026
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Atomic Scale Structural Studies of Macromolecular Assemblies by Solid-state Nuclear Magnetic Resonance Spectroscopy
Published on: September 17, 2017
The planar conformation of a strained proline ring: a QM/MM study
Serena Donnini1, Gerrit Groenhof, Rik K Wierenga
1The Biocenter and the Department of Biochemistry, University of Oulu, FIN-90014 University of Oulu, Finland.
Proteins
|June 3, 2006
Summary
Quantum mechanics calculations reveal that steric hindrance from nearby residues stabilizes a planar proline in triosephosphate isomerase (TIM). This planarity in the closed conformation may store energy for the enzyme's catalytic cycle.
Area of Science:
- Computational Chemistry
- Structural Biology
- Enzyme Catalysis
Background:
- Triosephosphate isomerase (TIM) is a crucial enzyme in glycolysis.
- The active site proline (Pro168) in TIM adopts a planar conformation in the liganded state.
- Understanding the factors governing proline conformation is key to elucidating enzyme mechanisms.
Purpose of the Study:
- To identify the structural and energetic origins of the planar proline conformation in TIM.
- To investigate the role of this conformation in the enzyme's catalytic cycle.
- To assess the accuracy of current computational methods for modeling strained protein fragments.
Main Methods:
- Quantum Mechanics (QM) and QM/Molecular Mechanics (QM/MM) energy calculations.
- Analysis of atomic resolution structures of liganded TIM.
- Comparison of proline conformations in open and closed TIM states using X-ray crystallography data.
Main Results:
- Steric interactions between Pro168 and neighboring tyrosine (Tyr166) and alanine (Ala171) residues prevent standard puckering.
- A sufficiently large quantum system, including nearby side chains (Tyr166, Ala171, Glu129), is necessary to accurately model the planar proline.
- The proline is planar in the closed TIM conformation and down-puckered in the open conformation.
Conclusions:
- The planarity of Pro168 in TIM is sterically enforced and requires accurate quantum mechanical treatment.
- Current force fields may not adequately represent strained protein fragments like the planar proline.
- The planar proline conformation in the closed state likely acts as an energy reservoir, released upon loop opening during catalysis.
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