title: Electrostatic coupling between retinal isomerization and the ionization state of Glu-204: a general mechanism for proton release in bacteriorhodopsin.
abstract: The pKa values of ionizable groups that lie between the active site region of bacteriorhodopsin (bR) and the extracellular surface of the protein are reported. Glu-204 is found to have an elevated pKa in the resting state of bR, suggesting that it corresponds to the proton-releasing group in bR. Its elevated pKa is predicted to be due in part to strong repulsive interactions with Glu-9. Following trans-cis isomerization of the retinal chromophore and the transfer of a proton to Asp-85, polar groups on the protein are able to interact more strongly with the ionized state of Glu-204, leading to a substantial reduction of its pKa. This suggests a general mechanism for proton release in which isomerization and subsequent charge separation initially produce a new electrostatic balance in the active site of bR. Here it is proposed that those events in turn drives a conformational change in the protein in which the ionized state of Glu-204 can be stabilized through interactions with groups that were previously inaccessible. Whether these groups should be identified with polar moieties in the protein, bound waters, or Arg-82 is an important mechanistic question whose elucidation will require further study.
authors.affiliation: Department of Biochemistry and Molecular Biophysics, Columbia University, New York, New York 10032, USA.
authors.forename: R V
authors.initials: RV
authors.lastname: Sampogna
authors.forename: B
authors.initials: B
authors.lastname: Honig
mesh_terms: D001436:Bacteriorhodopsins / Q000737:chemistry*; D001665:Binding Sites; D055592:Biophysical Phenomena; D001703:Biophysics; D018698:Glutamic Acid / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D007477:Ions; D007536:Isomerism; D008958:Models, Molecular; D015394:Molecular Structure; D011487:Protein Conformation; D011522:Protons; D012172:Retinaldehyde / Q000737:chemistry; D055672:Static Electricity
chemical_list: D007477:Ions; D011522:Protons; D018698:Glutamic Acid; D001436:Bacteriorhodopsins; D012172:Retinaldehyde