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

Smith, M.S.; Lawrence, Eliza E. K.; Billings, W.M.; Larsen, Kimberlee S.; Bécar, Natalie A.; Price, Joshua L.

doi:10.1021/acschembio.7b00768

Cited by 26 publications

(25 citation statements)

References 31 publications

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“…This observation casts doubt on the early assertion that the redder color for yellow fluorescent protein from wildtype GFP through the mutation of T203Y is achieved by the polarizability of the π system [34] [35], because a polarizable electronic system should be able to accommodate both cations and anions via redistribution of its electrons accordingly. Instead, it is the electron-rich nature of the π system that results in the overall stabilization of cations, which rationalizes the prevalence of cation-π over anion-π interactions in protein structures [36][37], also partially owing to the lack of naturally occurring amino acids bearing electron-deficient aromatic side chains such as F5F [38]. It is also satisfying to see that we are able to treat these interactions on an equal footing through models of electrostatic color tuning demonstrated in Figures 3A and 3B [39][40] [41].…”

Section: Stark Tuning Rate and Color Tuning Mechanismmentioning

confidence: 99%

Mechanism of Color and Photoacidity Tuning for the Protonated Green Fluorescent Protein Chromophore

Lin

Boxer²

2020

Preprint

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The neutral or A state of the green fluorescent protein (GFP) chromophore is a remarkable example of a photoacid naturally embedded in the protein environment and accounts for the large Stokes shift of GFP in response to near UV excitation. Its color tuning mechanism has been largely overlooked, as it is less preferable for imaging applications than the redder anionic or B state. Past studies, based on site-directed mutagenesis or solvatochromism of the isolated chromophore, have concluded that its color tuning range is much narrower than its anionic counterpart. However, as we performed extensive investigation on more GFP mutants, we found the color of the neutral chromophore to be much more sensitive to protein electrostatics. Electronic Stark spectroscopy reveals a fundamentally different electrostatic color tuning mechanism for the neutral state of the chromophore that demands a three-form model compared with that of the anionic state, which requires only two forms. Specifically, an underlying zwitterionic charge transfer state is required to explain its sensitivity to electrostatics. As the Stokes shift is tightly linked to the protonated chromophore’s photoacidity and excited-state proton transfer (ESPT), we infer design principles of the GFP chromophore as a photoacid through the color tuning mechanisms of both protonation states. The three-form model could also be applied to similar biological and nonbiological dyes and complements the failure of two-form model for donor–acceptor systems with localized electronic distributions.

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Section: Stark Tuning Rate and Color Tuning Mechanismmentioning

confidence: 99%

Mechanism of Color and Photoacidity Tuning for the Protonated Green Fluorescent Protein Chromophore

Lin

Boxer²

2020

Preprint

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“…[3][4][5][6][7][8][9][10][11][12][13][14] Though still largely underexplored comparing with cation- interactions, the importance of anion- interactions in biocatalysis, biomolecular recognition and in structure of macromolecules is increasingly recognized. [15][16][17][18][19][20][21][22][23][24][25] One distinguished property of anions is their wide shape variety, from spherical, linear, to triangular and polyhedral. However, the strength of anion- interactions involving polyhedral, e.g., tetrahedral or octahedral anions is generally weak owing to the large size and low electron density of these anions.…”

Section: Introductionmentioning

confidence: 99%

Naphthalene-Pillared Benzene Triimide Cage: An Efficient Receptor for Polyhedral Anions and a General Tool for Probing Theoretically-Existing Anion-π Binding Motifs

Tuo¹,

Ao²,

Wang³

et al. 2022

CCS Chem

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A triangular prism cage 2 with benzene triimide (BTI) as the bases, 2,7-naphthalene dimethyl as the supporting pillars was designed and synthesized efficiently. The two parallel BTI planes constitute a cavity of 7.58 Å which allows inclusion of anions of various sizes. Cage 2 showed so far the strongest binding affinity to a series of polyhedral (tetrahedral and octahedral) anions including PF 6 -(24651 M -1 ), ClO 4 -(28234 M -1 ), CH 3 SO 3 -(30571 M -1 ), BF 4 -(31613 M -1 ) and HSO 4 -(84623 M -1 ). The obtained eleven crystal structures of 2⸧Xcomplexes with different anions demonstrated that multiple and cooperative anion- interactions contribute synergistically to the strong complexation. The series of complex structures systematically suggested that cage 2 is a good, general tool for probing anion- binding motifs that have only been predicted in theoretical calculations. For anions of triangular (NO 3 -) and polyhedral (BF 4 -, ClO 4 -, PF 6 -) shapes, the as-predicted most stable anion- binding motifs with charge-neutral  systems were experimentally observed for the first time.

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“…This leading function of the polarizability has gained recognition from some recent experimental works where handling the polarizability of aromatic systems by means of -stacking [138][139][140] or external electric fields [141] were used to favour anion- interactions and made them useful in recognition of anion species or even in catalysis [51]. In agreement with these strategies for strengthening of anion- interactions through polarization modification, an exhaustive revision of the occurrence of anion- interactions in biomolecules [26] shows how modification of the polarization of aromatic rings is an extended strategy in biomolecules, such as proteins, DNA or RNA, to fortify anion- non-covalent bonds working for conformation stabilization [24,142].…”

Section: Anion-π and Lone Pair-π: Nature Of The Interactions And Relevance Of The S-tetrazine Ringmentioning

confidence: 88%

“…The lone pair-π [1][2][3][4][5][6][7] and anion-π [1,[8][9][10][11][12][13][14][15][16][17][18][19] interactions are emergent noncovalent forces whose occurrence has recently been recognized in both synthetic architectures [8,20,21] and biomolecular structures [4,[22][23][24][25][26] and are now taken into account for the construction of new functional materials [27][28][29][30][31][32][33][34], receptors [35][36][37][38][39][40][41][42][43] carriers [44][45][46]…”

Section: Introductionmentioning

confidence: 99%

Anion-π and lone pair-π interactions with s-tetrazine-based ligands

Savastano

García-Gallarín

Torre

et al. 2019

Coordination Chemistry Reviews

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Most of traditional and contemporary interest in s-tetrazine derivatives focuses onto their redox properties, reactivity and energy density. In recent times, however, an increasing number of reports highlighted the possible usefulness of the s-tetrazine moiety as a binding site for anionic and electron rich species, according to the high and positive quadrupolar moment of this heterocycle and the consequent strength of anion-π and lone pair-π interactions. Herein, after giving a quick perspective on s-tetrazine properties and on how they foster these types of π interactions, we present statistical and critical examination of the available structural data, doing justice to the debated topic of the existence and directionality of anion-and lone pair-π interactions. Finally, available literature material concerning the usage of s-tetrazine as supramolecular binding site in solution, i.e. paving the way to applications such as molecular recognition and sensing, is presented and discussed. Contents 1. Introduction 2. s-Tetrazine Synthesis & Properties 2.1. Synthesis of s-tetrazine derivatives 2.2. General perspective on the properties and applications s-tetrazines 2.3. Anion-π and lone pair-π: nature of the interactions and relevance of the s-tetrazine ring 3. Anion-π and lone pair-π interactions with s-tetrazines in the solid-state: CSD Survey 3.1. Methodology and rationale of the survey 3.2. Structural data analysis 4. Selected evidences of anion-π and lone pair-π interactions with s-tetrazines in the solid state 5. Anion-π and lone pair-π interactions with s-tetrazines in solution 6. Conclusions Appendix A. Supplementary data Referencesthe aromatic s-tetrazine ring enables compact molecular packings which are essential to realize substances with a high (volumetric) energy density [116,117]. This is a field that continues very active in seeking for new s-tetrazine derivatives of interest [118][119][120].Other important applications of s-tetrazines derive from their particular reactivity, that serves as the base of the usefulness that these structures are proving in molecular biology studies, as reacting partners in bioorthogonal chemistry [121] methods (a field that has boosted the research and literature devoted to stetrazines from the first 2000s) [84,122]. These applications take advantage of two properties of stetrazines: i) the propensity of the s-tetrazine nucleus to act as 2,3-diazadiene in fast inverse-electrondemand Diels-Alder (iedDA) reactions with alkenes and alkynes that affords, in a first term, a bicyclic adduct which immediately suffers a retro-Diels-Alder (rDA) reaction, evolving N 2 , to give rise to dihydropyridazines or aromatic pyridazines, respectively (Scheme 2) [123,124]; ii) the inertness of s-tetrazine derivatives towards natural substances under biological conditions. Scheme 2 to be inserted about here.But the property that focused our interest in s-tetrazines, and constitutes the main subject of this review, is their ability to establish non-covalent bonds to negatively charged species (a...

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

Cited by 26 publications

References 31 publications

Mechanism of Color and Photoacidity Tuning for the Protonated Green Fluorescent Protein Chromophore

Mechanism of Color and Photoacidity Tuning for the Protonated Green Fluorescent Protein Chromophore

Naphthalene-Pillared Benzene Triimide Cage: An Efficient Receptor for Polyhedral Anions and a General Tool for Probing Theoretically-Existing Anion-π Binding Motifs

Anion-π and lone pair-π interactions with s-tetrazine-based ligands

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