Homology modeling, molecular dynamics simulations, and analysis of CYP119, a P450 enzyme from extreme acidothermophilic archaeon Sulfolobus solfataricus.

The recent characterization of a thermophilic and barophilic CYP119 from Sulfolobus solfataricus offers a new opportunity to identify the origin of its stability by comparing it with mesophilic P450s with known structures. Since the three-dimensional structure of CYP119 is not yet available, homology modeling techniques were used to build model structures for this enzyme. The overall quality and stability of the models were assessed using three protein analysis programs and by monitoring structural stability during 1 ns of molecular dynamics simulations at 300 and 390 K. The results show the CYP119 models to be of good quality. Possible origins of the thermo- and barostability of CYP119 were then investigated by examining the amino acid compositions and the three-dimensional structure of CYP119 compared with the five mesophilic templates. Three possible factors were identified that could contribute to the enhanced stability of CYP119. The first was the higher relative population of salt bridges and the pr...