ArticleJournal of the American Chemical Society2010
The aberrance of the 4S diastereomer of 4-hydroxyproline.
Article in Journal of the American Chemical Society, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
26 citing papers in PubMed, 70 citations in OpenAlex.
- Plasma 4-Hydroxyproline Levels Are Associated with Diabetes in Chinese Adults: A Cross-Sectional Analysis.Metabolites · 2026Article
- Stereoelectronic and hydrogen-bonding effects on hydroxyproline conformation.Communications chemistry · 2026Article
- Molecular foundations of collagen triple helical assembly: the central role of prolyl-4-hydroxylation.The Biochemical journal · 2026Review
- Stereoselective Preparation of (Molbank · 2025Article
- Cis-trans isomerization of peptoid residues in the collagen triple-helix.Nature communications · 2023Article
- Clickable Polyprolines from Azido-prolineACS polymers Au · 2023Article
- Consequences of incorporating thiaproline and its oxidized derivatives into collagen triple helices.Protein science : a publication of the Protein Society · 2023Article
- Article
- Conformation and Morphology of 4-(NHACS omega · 2020Article
- Conformational landscape of substituted prolines.Biophysical reviews · 2020Review
- The Distinct Conformational Landscapes of 4S-Substituted Prolines That Promote an endo Ring Pucker.Chemistry (Weinheim an der Bergstrasse, Germany) · 2019Article
- Secondary Forces in Protein Folding.ACS chemical biology · 2019Review
- n→π* Interactions Modulate the Properties of Cysteine Residues and Disulfide Bonds in Proteins.Journal of the American Chemical Society · 2018Article
- 3-Fluoro-4-hydroxyprolines: Synthesis, Conformational Analysis, and Stereoselective Recognition by the VHL E3 Ubiquitin Ligase for Targeted Protein Degradation.Journal of the American Chemical Society · 2018Article
- The n→π* Interaction.Accounts of chemical research · 2017Article
- 4S-Hydroxylation of Insulin at ProB28 Accelerates Hexamer Dissociation and Delays Fibrillation.Journal of the American Chemical Society · 2017Article
- Diversity of Secondary Structure in Catalytic Peptides with β-Turn-Biased Sequences.Journal of the American Chemical Society · 2017Article
- n→π* Interactions Are Competitive with Hydrogen Bonds.Organic letters · 2016Article
- 4R- and 4S-iodophenyl hydroxyproline, 4R-pentynoyl hydroxyproline, and S-propargyl-4-thiolphenylalanine: conformationally biased and tunable amino acids for bioorthogonal reactions.Organic & biomolecular chemistry · 2016Article
- Thioamides in the collagen triple helix.Chemical communications (Cambridge, England) · 2015Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Prolyl 4-hydroxylases install a hydroxyl group in the 4R configuration on the gamma-carbon atom of certain (2S)-proline (Pro) residues in tropocollagen, elastin, and other proteins to form (2S,4R)-4-hydroxyproline (Hyp). The gauche effect arising from this prevalent post-translational modification enforces a C(gamma)-exo ring pucker and stabilizes the collagen triple helix. The Hyp diastereomer (2S,4S)-4-hydroxyproline (hyp) has not been observed in a protein, despite the ability of electronegative 4S substituents to enforce the more common C(gamma)-endo ring pucker of Pro. Here, we use density functional theory, spectroscopy, crystallography, and calorimetry to explore the consequences of hyp incorporation on protein stability using a collagen model system. We find that the 4S-hydroxylation of Pro to form hyp does indeed enforce a C(gamma)-endo ring pucker but a transannular hydrogen bond between the hydroxyl moiety and the carbonyl of hyp distorts the main-chain torsion angles that typically accompany a C(gamma)-endo ring pucker. This same transannular hydrogen bond enhances an n-->pi* interaction that stabilizes the trans conformation of the peptide bond preceding hyp, endowing hyp with the unusual combination of a C(gamma)-endo ring pucker and high trans/cis ratio. O-Methylation of hyp to form (2S,4S)-4-methoxyproline (mop) eliminates the transannular hydrogen bond and restores a prototypical C(gamma)-endo pucker. mop residues endow the collagen triple helix with much more conformational stability than do hyp residues. These findings highlight the critical importance of the configuration of the hydroxyl group installed on C(gamma) of proline residues.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.