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  • Title: Mapping proton wires in proteins: carbonic anhydrase and GFP chromophore biosynthesis.
    Author: Shinobu A, Agmon N.
    Journal: J Phys Chem A; 2009 Jul 02; 113(26):7253-66. PubMed ID: 19388648.
    Abstract:
    We have developed an algorithm for mapping proton wires in proteins and applied it to the X-ray structures of human carbonic anhydrase II (CA-II), the green fluorescent protein (GFP), and some of their mutants. For both proteins, we find more extensive proton wires than typically reported. In CA-II the active site wire exits to the protein surface, and leads to Glu69 and Asp72, located on an electronegative patch on the rim of the active site cavity. One possible interpretation of this observation is that positively charged, protonated buffer molecules dock in that area, from which a proton is delivered to the active site when the enzyme works in the dehydration direction. In GFP we find a new internal proton wire, in addition to the previously reported wire involved in excited state proton transfer. The new wire is located on the other face of the chromophore, and we conjecture that it plays a role in chromophore biosynthesis that occurs following protein folding. In the last step of this process, transient carbanion formation was suggested to occur on the bridge carbon [Pouwels et al. Biochemistry 2008, 47, 10111]. Residues on the new wire (Thr62, His181, Arg96) may participate in proton abstraction from this bridge carbon atom. A possible mechanism involves a rotation of the Thr62 side chain and completion of a short wire by which the proton is transported to His181, while the negative charge is transferred to the imidazolone carbonyl, producing a homoenolate intermediate that is stabilized by Arg96. Finally, comparison of the proton wires in the two proteins reveals common motifs, such as short internalized Ser/Thr-Glu hydrogen-bonded pairs for ultrafast proton abstraction, and threonine side chain rotation functioning as a proton wire switch.
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