Insights from the salt bridge analysis of malate dehydrogenase from H. salinarum and E.coli.

Halophilic proteins have greater abundance of acidic over basic residues in sequence. In structure, the surface is decorated by negative charges, with lower content of Lysine. Using sequence BLOCKs and 3D model of malate dehydrogenase from halophilic archaea (Halobacterium salinarum; hsMDH) and X-ray structure from mesophilic bacteria (E. coli; ecMDH), we show that not only acidic and basic residues have higher mean relative abundance (MRA) and thus, impart higher polarity to the sequences, but also show their presence in the surface of the structure of hsMDH relative to its mesophilic counterpart. These observations may indicate that both the acidic and the basic residues have a concerted role in the stability of hsMDH. Analysis on salt bridges from hsMDH and ecMDH show that in the former, salt bridges are highly intricate, newly engineered and global in nature. Although, these salt bridges are abundant in hsMDH, in the active site the design remains unperturbed. In high salt where hydrophobic force is weak, these salt bridges seem to play a major role in the haloadaptation of the tertiary structure of hsMDH. This is the first report of such an observation.