A structure-based model for the halophilic adaptation of dihydrofolate reductase from Halobacterium volcanii.
'Halophilic adaptation' of proteins, i.e. the requirement for high concentrations of monovalent ions for thermodynamic stability of proteins from halophilic organisms, is not fully understood. In this work, an explanation for the halophilic behavior of dihydrofolate reductase (h-DHFR) from Halobacterium volcanii is attempted, based on a model structure derived from comparative modeling to dihydrofolate reductase from Escherichia coli. The model structure of h-DHFR shows an unique asymmetrical charge distribution over the protein surface, with positively charged amino acids centered around the active site and negative charges on the opposite side of the enzyme. This particular charge distribution and the correlated molecular dipole are functionally relevant. The negative charges on the surface form clusters which are shielded at high salt concentrations; at low salt, they repulse each other, thus destabilizing the protein. Results are in accordance with denaturation data and, thus, provide an explanation for the exceptional stability properties of h-DHFR.
Böhm
G
G
Institut für Biophysik und Physikalische Biochemie, Universität Regensburg, Germany.
Jaenicke
R
R
D000595:Amino Acid Sequence; D001419:Bacteria / Q000201:enzymology; D001426:Bacterial Proteins / Q000737:chemistry*; D002414:Cations, Monovalent / Q000737:chemistry*; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D003198:Computer Simulation; D004926:Escherichia coli / Q000201:enzymology; D006217:Halobacterium / Q000201:enzymology*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010802:Phylogeny; D011489:Protein Denaturation; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D013045:Species Specificity; D013762:Tetrahydrofolate Dehydrogenase / Q000737:chemistry*
D001426:Bacterial Proteins; D002414:Cations, Monovalent; D013762:Tetrahydrofolate Dehydrogenase