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Inductive effects on the structure of proline residues
N Panasik1, E S Eberhardt, A S Edison
1Department of Biochemistry, University of Wisconsin-Madison.
International Journal of Peptide and Protein Research
|September 1, 1994
Summary
The structure of proline residues in collagen is significantly influenced by electron-withdrawing substituents. This study reveals how 4(S)-hydroxyproline (Hyp) affects proline structure, impacting protein conformation and isomerization rates.
Area of Science:
- Structural Biology
- Biochemistry
- Computational Chemistry
Background:
- 4(S)-Hydroxyproline (Hyp) is a key component of collagen, comprising approximately 10% of this abundant vertebrate protein.
- The inductive effect of the hydroxyl group in Hyp residues may influence the structural characteristics of proline residues within collagen.
- Understanding these structural effects is crucial for comprehending collagen's overall function and stability.
Purpose of the Study:
- To investigate the impact of electron-withdrawing substituents at the 4-position of proline residues on their molecular structure.
- To determine how the hydroxyl group of Hyp influences the conformation and bond characteristics of proline.
- To correlate structural changes with potential alterations in prolyl peptide bond isomerization rates.
Main Methods:
- Synthesis of N-acetylproline methylester (1), N-acetyl-4(S)-hydroxyproline methylester (2), and N-acetyl-4(S)-fluoroproline methylester (3).
- High-resolution X-ray diffraction analysis to determine the crystalline structures of synthesized compounds.
- Ab initio molecular orbital calculations (RHF/3-21G) to predict and compare bond lengths.
Main Results:
- Compound 1 exhibited cis amide bond and C gamma-endo pucker of the pyrrolidine ring.
- Compounds 2 and 3 showed trans amide bonds and C-exo pucker, with significantly shorter sp3-hybridized carbon-carbon bonds compared to compound 1.
- A dramatic increase in nitrogen atom pyramidylization was observed in the order 1 < 2 < 3, indicating increased sp3-character.
Conclusions:
- Electron-withdrawing substituents at the 4-position of proline residues significantly influence their structure, particularly nitrogen atom pyramidylization.
- These structural modifications, including altered bond lengths and ring puckering, suggest a potential impact on the rate of prolyl peptide bond isomerization.
- The findings provide insights into the structure-function relationship of collagen and the role of Hyp in protein stability and dynamics.