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Mapping Proton Wires in Proteins: Carbonic Anhydrase and GFP Chromophore Biosynthesis
 

Summary: Mapping Proton Wires in Proteins: Carbonic Anhydrase and GFP Chromophore
Biosynthesis
Ai Shinobu and Noam Agmon*
Fritz Haber Research Center, Institute of Chemistry, The Hebrew UniVersity of Jerusalem,
Jerusalem 91904, Israel
ReceiVed: NoVember 20, 2008; ReVised Manuscript ReceiVed: March 3, 2009
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.

  

Source: Agmon, Noam - Institute of Chemistry, Hebrew University of Jerusalem

 

Collections: Chemistry