Member # 1
posted 18. July 2005 15:59
PNAS Early Edition, May 13
Three-dimensional structure of a halotolerant algal carbonic anhydrase predicts halotolerance of a mammalian homolog
Lakshmanane Premkumar, Harry M. Greenblatt, Umesh K. Bageshwar, Tatyana Savchenko, Irena Gokhman, Joel L. Sussman, and Ada Zamir
Protein molecular adaptation to drastically shifting salinities was studied in dCA II, an alpha-type carbonic anhydrases except for two extended alphahelices and an added Na-binding loop. Its unusual electrostatic properties include a uniformly negative surface electrostatic potential of lower magnitude than that observed in the highly acidic halophilic proteins and an exceptionally low positive potential at a site adjoining the catalytic Zn2+ compared with mesophilic homologs. The halotolerant dCA II also differs from typical halophilic proteins in retaining conformational stability and solubility in low to high salt concentrations. The crucial role of electrostatic features in dCA II halotolerance is strongly supported by the ability to predict the unanticipated halotolerance of the murine CA XIV isozyme, which was confirmed biochemically. A proposal for the functional significance of the halotolerance of CA XIV in the kidney is presented.