An Anion−π Interaction Strongly Stabilizes the β‑Sheet Protein WW

• Published in: ACS chemical biology Vol. 12; no. 10; pp. 2535 - 2537
• Main Authors: Smith, Mason S, Lawrence, Eliza E. K, Billings, Wendy M, Larsen, Kimberlee S, Bécar, Natalie A, Price, Joshua L
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 20.10.2017
• Subjects: Amino Acid Sequence; Amino Acids - chemistry; Models, Molecular; NIMA-Interacting Peptidylprolyl Isomerase - chemistry; Protein Conformation, beta-Strand; Protein Domains
• ISSN: 1554-8929; 1554-8937; 1554-8937
• DOI: 10.1021/acschembio.7b00768

Anions have long been known to engage in stabilizing interactions with electron-deficient arenes. However, the precise nature and energetic contribution of anion−π interactions to protein stability remains a subject of debate. Here, we show that placing a negatively charged Asp in close proximity to electron-rich Phe in a reverse turn within the WW domain results in a favorable interaction that increases WW conformational stability by −1.3 kcal/mol.