Halophilic adaptation: Novel solvent protein interactions observed in the 2.9 and 2.6 a resolution structures of the wild type and a mutant of malatedehydrogenase from Haloarcula marismortui

Previous biophysical studies of tetrameric malate dehydrogenase from the ha lophilic archaeon Haloarcula marismortui (Hm MalDH) have revealed the impor tance of protein-solvent interactions for its adaptation to molar salt cond itions that strongly affect protein solubility, stability, and activity, in general. The structures of the E267R stability mutant of apo (-NADH) Hm Ma lDH determined to 2.6 Angstrom resolution and of apo (-NADH) wild type Hot MalDH determined to 2.9 Angstrom resolution, presented here, highlight a va riety of novel protein-solvent features involved in halophilic adaptation. The tetramer appears to be stabilized by ordered water molecule networks an d intersubunit complex salt bridges "locked" in by bound solvent chloride a nd sodium ions. The E267R mutation points into a central ordered water cavi ty, disrupting protein-solvent interactions. The analysis of the crystal st ructures showed that halophilic adaptation is not aimed uniquely at "protec ting" the enzyme from the extreme salt conditions, as may have been expecte d, but, on the contrary, consists of mechanisms that harness the high ionic concentration in the environment.