In a recent paper published in the Proceedings of the National Academy of Sciences, USA (PNAS), Institute scientists Prof. Ada Zamir and Dr. Lakshmanane Premkumar of the Institute's Biological Chemistry Department and Prof. Joel Sussman and Dr. Harry Greenblatt of the Structural Biology Department revealed the structural basis of a remarkably salt-tolerant Dunaliella enzyme, a carbonic anhydrase, which may hold the key. Comparisons with known carbon anhydrases from animal sources showed that the Dunaliella enzyme shares a basic plan with its distant relatives, but with a few obvious differences. The most striking of these is in the electrical charges on the proteins' surfaces: Charges on the salt-tolerant enzyme are uniformly negative (though not as intensely negative as those in halophilic proteins), while the surfaces of carbonic anhydrases that don't tolerate salt sport a negative/positive/ neutral mix. This and other unique structural features may enable the algal carbonic anhydrase to be active in the presence of salt, though not dependent on it. In a surprise twist, the researchers discovered that one other known carbonic anhydrase - found in mouse kidney - sported a similar, salt-tolerant construction. Pondering why a structure conferring salt tolerance should evolve once in a Dead Sea organism and once in a mouse has led the researchers to some new insights into kidney physiology. The researchers hope that the knowledge gleaned from their study of a tiny alga might provide the basis for designing new drugs that could target enzymes based on their salt tolerance.
Prof. Joel Sussman's research is funded by the Helen and Milton A. Kimmelman Center for Biomolecular Structure and Assembly; the Joseph and Ceil Mazer Center for Structural Biology; the Charles A. Dana Foundation; the Divadol Foundation; the Jean and Jula Goldwurm Memorial Foundation; the late Sally Schnitzer, New York, NY; the Kalman and Ida Wolens Foundation; and the Wolfson Family Charitable Trust. Prof. Joel Sussman is the incumbent of the Morton and Gladys Pickman Chair in Structural Biology.