Aza-proline effectively mimics L-proline stereochemistry in triple helical collagen
Abstract
The prevalence of L-amino acids in biomolecules has been shown to have teleological importance in biomolecular structure and self-assembly. Recently, biophysical studies have demonstrated that natural L-amino acids can be replaced with non-natural achiral aza-amino acids in folded protein structures such as triple helical collagen. However, the structural consequences of achiral aza-amino acid incorporation has not been elucidated in the context of any relevant folded biomolecule. Herein, we use X-ray crystallography to provide the first atomic resolution crystal structure of an achiral aza-amino acid residue embedded within a folded protein structure, definitively illustrating that achiral aza-proline has the capacity to effectively mimic the stereochemistry of natural amino acids within the context of triple helical collagen. We further corroborate this finding with density functional theory computational analysis showing that the natural L-amino acid stereochemistry for aza-proline is energetically favored when arranged in the aza-proline-hydroxyproline-glycine motif. In addition to providing fundamental insight into peptide and protein structure, the incorporation of achiral stereochemical mimics such as aza-amino acids could have far reaching impacts in areas ranging from synthetic materials to drug design.
- Publication Date:
- Research Org.:
- Argonne National Lab. (ANL), Argonne, IL (United States). Advanced Photon Source (APS)
- Sponsoring Org.:
- National Science Foundation (NSF); University of Pennsylvania; National Institutes of Health (NIH)
- OSTI Identifier:
- 1599449
- Grant/Contract Number:
- DMR-1720530
- Resource Type:
- Accepted Manuscript
- Journal Name:
- Chemical Science
- Additional Journal Information:
- Journal Volume: 10; Journal Issue: 29; Journal ID: ISSN 2041-6520
- Publisher:
- Royal Society of Chemistry
- Country of Publication:
- United States
- Language:
- ENGLISH
- Subject:
- 37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY
Citation Formats
Kasznel, Alexander J., Harris, Trevor, Porter, Nicholas J., Zhang, Yitao, and Chenoweth, David M. Aza-proline effectively mimics L-proline stereochemistry in triple helical collagen. United States: N. p., 2019.
Web. doi:10.1039/C9SC02211B.
Kasznel, Alexander J., Harris, Trevor, Porter, Nicholas J., Zhang, Yitao, & Chenoweth, David M. Aza-proline effectively mimics L-proline stereochemistry in triple helical collagen. United States. https://doi.org/10.1039/C9SC02211B
Kasznel, Alexander J., Harris, Trevor, Porter, Nicholas J., Zhang, Yitao, and Chenoweth, David M. Fri .
"Aza-proline effectively mimics L-proline stereochemistry in triple helical collagen". United States. https://doi.org/10.1039/C9SC02211B. https://www.osti.gov/servlets/purl/1599449.
@article{osti_1599449,
title = {Aza-proline effectively mimics L-proline stereochemistry in triple helical collagen},
author = {Kasznel, Alexander J. and Harris, Trevor and Porter, Nicholas J. and Zhang, Yitao and Chenoweth, David M.},
abstractNote = {The prevalence of L-amino acids in biomolecules has been shown to have teleological importance in biomolecular structure and self-assembly. Recently, biophysical studies have demonstrated that natural L-amino acids can be replaced with non-natural achiral aza-amino acids in folded protein structures such as triple helical collagen. However, the structural consequences of achiral aza-amino acid incorporation has not been elucidated in the context of any relevant folded biomolecule. Herein, we use X-ray crystallography to provide the first atomic resolution crystal structure of an achiral aza-amino acid residue embedded within a folded protein structure, definitively illustrating that achiral aza-proline has the capacity to effectively mimic the stereochemistry of natural amino acids within the context of triple helical collagen. We further corroborate this finding with density functional theory computational analysis showing that the natural L-amino acid stereochemistry for aza-proline is energetically favored when arranged in the aza-proline-hydroxyproline-glycine motif. In addition to providing fundamental insight into peptide and protein structure, the incorporation of achiral stereochemical mimics such as aza-amino acids could have far reaching impacts in areas ranging from synthetic materials to drug design.},
doi = {10.1039/C9SC02211B},
journal = {Chemical Science},
number = 29,
volume = 10,
place = {United States},
year = {Fri Jun 21 00:00:00 EDT 2019},
month = {Fri Jun 21 00:00:00 EDT 2019}
}
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