دورية أكاديمية
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4,4-Difluoroproline as a Unique 19 F NMR Probe of Proline Conformation.

التفاصيل البيبلوغرافية
العنوان: 4,4-Difluoroproline as a Unique 19 F NMR Probe of Proline Conformation.
المؤلفون: Ganguly HK; Department of Chemistry and Biochemistry, University of Delaware, Newark, Delaware 19716, United States., Ludwig BA; Department of Chemistry and Biochemistry, University of Delaware, Newark, Delaware 19716, United States., Tressler CM; Department of Chemistry and Biochemistry, University of Delaware, Newark, Delaware 19716, United States., Bhatt MR; Department of Chemistry and Biochemistry, University of Delaware, Newark, Delaware 19716, United States., Pandey AK; Department of Chemistry and Biochemistry, University of Delaware, Newark, Delaware 19716, United States., Quinn CM; Department of Chemistry and Biochemistry, University of Delaware, Newark, Delaware 19716, United States., Bai S; Department of Chemistry and Biochemistry, University of Delaware, Newark, Delaware 19716, United States., Yap GPA; Department of Chemistry and Biochemistry, University of Delaware, Newark, Delaware 19716, United States., Zondlo NJ; Department of Chemistry and Biochemistry, University of Delaware, Newark, Delaware 19716, United States.
المصدر: Biochemistry [Biochemistry] 2024 May 07; Vol. 63 (9), pp. 1131-1146. Date of Electronic Publication: 2024 Apr 10.
نوع المنشور: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.
اللغة: English
بيانات الدورية: Publisher: American Chemical Society Country of Publication: United States NLM ID: 0370623 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1520-4995 (Electronic) Linking ISSN: 00062960 NLM ISO Abbreviation: Biochemistry Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Washington, American Chemical Society.
مواضيع طبية MeSH: Proline*/chemistry , Proline*/analogs & derivatives , Fluorine*/chemistry, Crystallography, X-Ray/methods ; Protein Conformation ; Magnetic Resonance Spectroscopy/methods ; Peptides/chemistry ; Nuclear Magnetic Resonance, Biomolecular/methods ; Molecular Conformation
مستخلص: Despite the importance of proline conformational equilibria ( trans versus cis amide and exo versus endo ring pucker) on protein structure and function, there is a lack of convenient ways to probe proline conformation. 4,4-Difluoroproline (Dfp) was identified to be a sensitive 19 F NMR-based probe of proline conformational biases and cis-trans isomerism. Within model compounds and disordered peptides, the diastereotopic fluorines of Dfp exhibit similar chemical shifts (Δδ FF = 0-3 ppm) when a trans X-Dfp amide bond is present. In contrast, the diastereotopic fluorines exhibit a large (Δδ FF = 5-12 ppm) difference in chemical shift in a cis X-Dfp prolyl amide bond. DFT calculations, X-ray crystallography, and solid-state NMR spectroscopy indicated that Δδ FF directly reports on the relative preference of one proline ring pucker over the other: a fluorine which is pseudo-axial (i.e., the pro-4 R -F in an exo ring pucker, or the pro-4 S -F in an endo ring pucker) is downfield, while a fluorine which is pseudo-equatorial (i.e., pro-4 S -F when exo , or pro-4 R -F when endo ) is upfield. Thus, when a proline is disordered (a mixture of exo and endo ring puckers, as at trans -Pro in peptides in water), it exhibits a small Δδ. In contrast, when the Pro is ordered (i.e., when one ring pucker is strongly preferred, as in cis -Pro amide bonds, where the endo ring pucker is strongly favored), a large Δδ is observed. Dfp can be used to identify inherent induced order in peptides and to quantify proline cis-trans isomerism. Using Dfp, we discovered that the stable polyproline II helix (PPII) formed in the denatured state (8 M urea) exhibits essentially equal populations of the exo and endo proline ring puckers. In addition, the data with Dfp suggested the specific stabilization of PPII by water over other polar solvents. These data strongly support the importance of carbonyl solvation and n → π* interactions for the stabilization of PPII. Dfp was also employed to quantify proline cis - trans isomerism as a function of phosphorylation and the R406W mutation in peptides derived from the intrinsically disordered protein tau. Dfp is minimally sterically disruptive and can be incorporated in expressed proteins, suggesting its broad application in understanding proline cis - trans isomerization, protein folding, and local order in intrinsically disordered proteins.
المشرفين على المادة: 9DLQ4CIU6V (Proline)
284SYP0193 (Fluorine)
0 (Peptides)
تواريخ الأحداث: Date Created: 20240410 Date Completed: 20240507 Latest Revision: 20240507
رمز التحديث: 20240507
DOI: 10.1021/acs.biochem.3c00697
PMID: 38598681
قاعدة البيانات: MEDLINE
الوصف
تدمد:1520-4995
DOI:10.1021/acs.biochem.3c00697