The Existence of an Isolated Hydronium Ion in the Interior of Proteins

Abstract

Water molecules can serve as the proton donor and acceptor in the hydrogen bond (H-bond) network of the protein interior,f orming ap roton transfer pathway with titratable residues.I np articular, when water molecules are strongly H-bonded, the activation energy for proton transfer is the lowest, without involving formation of an isolated hydronium ion, H 3 O + .[1] On the other hand, H 3 O + was proposed to be present in H, K-ATPase [2] or at the end of the proton transfer pathway in bacteriorhodopsin [3] (but see also Ref.[4] ). In contrast, "isolated H 3 O + ", which exists in the absence of other water molecules,was not identified in protein crystal structures until neutron diffraction analysis of metal-removed d-xylose isomerase (XI) [6] and the more recent neutron diffraction analysis of phycocyanobilin-ferredoxin oxidoreductase (PcyA) [7] were reported. It has been proposed that in the PcyAneutron structure,H 3 O + donates H-bonds to Nd of His74, Ne of His88, and the backbone carbonyl Oo fL eu243 (Figure 1a). [7] TheH -bond network of the H 3 O + -binding moiety is also proposed to be involved in the proton transfer pathway,w hich would be necessary for the endovinyl reduction of biliverdin IXa.[8] In the XI neutron structure,H 3 O + was proposed to donate Hbonds to Glu181, Glu217, and Asp245, which was originally the metal-binding moiety of the enzyme [6] (Figure 1b) )i sÀ1.7, which is significantly lower than that for Asp (4.0), Glu (4.4), Nd of His (6.6), and Ne of His (7.0) in water.Thep K a of H-bond donor and acceptor moieties in Hbonds can be analyzed from the potential energy profiles of the H-bonds (Supporting Information, Figure S1). [9] In Hbonds,aproton is more likely to populate the moiety with the higher pK a value between the two moieties (Supporting Information, Figure S2).[9c] Thee nergy difference between the H-bond donor and acceptor moieties corresponds to the pK a difference (Supporting Information, Figure S3). This feature also holds true for H-bonds in protein environments, [9b,c,10] which are typically analyzed at the density functional theory (DFT) level. Calculations performed at the DFT level are likely to stray away from correct

Water Bridges Conduct Sequential Proton Transfer in Photosynthetic Oxygen Evolution

“…In bacteriorhodopsin, the positions of bound water molecules are dynamic and similar frequencies are observed in mutants . Interestingly, neutron diffraction has also provided evidence for isolated hydronium ions in proteins, stabilized by interactions with carbonyl groups and imidazole side chains . In PSII, W n + is observed in the S 2 -minus-S 1 spectrum and on the time scale of the S 2 transition.…”

Protein Motifs for Proton Transfers That Build the Transmembrane Proton Gradient

“…Rather it is associated with a water (hydronium, H 3 O + ) or two water molecules as a Zundel cation (H 5 O 2 + ) or as a larger, Eigen complex (H 9 O 4 + ) (Agmon, 1995;Wraight, 2006;Farahvash and Stuchebrukhov, 2018). In proteins, the proton can also be bound to redox cofactors, to acidic or basic residues or trapped as a stabilized hydronium (Xu and Voth, 2006;Freier et al, 2011;Ikeda et al, 2017).…”