A tyrosine–tryptophan dyad and radical-based charge transfer in a ribonucleotide reductase-inspired maquette

Abstract

In class 1a ribonucleotide reductase (RNR), a substrate-based radical is generated in the α2 subunit by long-distance electron transfer involving an essential tyrosyl radical (Y122O·) in the β2 subunit. The conserved W48 β2 is ∼10 Å from Y122OH; mutations at W48 inactivate RNR. Here, we design a beta hairpin peptide, which contains such an interacting tyrosine–tryptophan dyad. The NMR structure of the peptide establishes that there is no direct hydrogen bond between the phenol and the indole rings. However, electronic coupling between the tyrosine and tryptophan occurs in the peptide. In addition, downshifted ultraviolet resonance Raman (UVRR) frequencies are observed for the radical state, reproducing spectral downshifts observed for β2. The frequency downshifts of the ring and CO bands are consistent with charge transfer from YO· to W or another residue. Such a charge transfer mechanism implies a role for the β2 Y-W dyad in electron transfer.

Sampling the protonation states: the pH-dependent UV absorption spectrum of a polypeptide dyad

“…When going to acidic to basic pH, the distance between W14 and D3 slightly increases while the the distance between W14 and D11 decreases by 2Å. Finally, at variance with results indicated by Pagba et al, 16 our simulations do not show evidence of strong (hydrogen-bond) interactions between Y5 and R16, the corresponding distance being always larger than 17Å.…”

“…There is also an additional red-shift of a few nm at pH=5 with respect to tyrosine in water. Quoting, 16 "the red shift of the tyrosine ultraviolet spectrum in Peptide M is attributable to the close proximity of the cross-strand Y5 and W14 to form a Y5-W14 dyad." It is rightful, being the experimental pK a of the tyrosine side chain in water ∼ 10.9, 17 to attribute this behavior to the deprotonation occurring at basic pH; however, the presence of two other titratable residues, aspartic acids D3 and D11, contributes to the complexity of the protonation microstates landscape.…”

“…The absorption spectra were generated at room temperature with normalized Lorentzian functions from the excitation energies for the first four excited states and the corresponding oscillator strengths using Newton-X 2.0, 24,25 which adopts the nuclear ensemble approach. 26 Data of the experimental spectra published in 16 0.96, 1.07 and 0.93 for D3, Y5 and D11 respectively. In other words, these titrable residues are interacting negligibly in the protonation state space.…”

Structural characterizations of human periostin dimerization and cysteinylation

“…The aromatic residues Trp63, Tyr64, and Tyr77, within the distance range of 4 Å around Cys60 (Fig. S8A), might get involved in proton‐coupled electron transfer during such a redox process, similar to the cases of natural and biomimetic systems . During this process, human periostin would consistently act as a dimer, since mutation of Cys60 to Ala did not alter the dimerization mode of periostin (Fig.…”

Tyrosine‐Rich Peptides as a Platform for Assembly and Material Synthesis

“…Tyrosine with a redox-active phenol group has been proposed to play an important role in several enzymes, including photosystem II (PS2), [32,33] ribonucleotide reductase, [34] prostaglandin synthase, [35] cytochrome c oxidase, [28] and galactose oxidase. Inspired by the role of tyrosine in enzymatic systems and photosynthesis, numerous model studies have been conducted on structurally defined biomimetic peptides, such as a β-hairpin Tyr-containing peptide designed de novo [37] and a Tyr-conjugated metal-ligand complex. It plays a critical role as a redox intermediate between the Mn 4 Ca cluster and the central chlorophylls, denoted as P 680 from their lowest absorption maximum at 680 nm.…”