Palmer, D. S. and Christensen, A. U. and Sørensen, J. and Celik, L. and Qvist, K. B. and Schiøtt, B. (2010) Bovine chymosin: a computational study of recognition and binding of bovine kappa-casein. Biochemistry, 49 (11). pp. 2563-2573.Full text not available in this repository. (Request a copy from the Strathclyde author)
Bovine chymosin is an aspartic protease that selectively cleaves the milk protein kappa-casein. The enzyme is widely used to promote milk clotting in cheese manufacturing. We have developed models of residues 97-112 of bovine kappa-casein complexed with bovine chymosin, using ligand docking, conformational search algorithms, and molecular dynamics simulations. In agreement with limited experimental evidence, the model suggests that the substrate binds in an extended conformation with charged residues on either side of the scissile bond playing an important role in stabilizing the binding pose. Lys111 and Lys112 are observed to bind to the N-terminal domain of chymosin displacing a conserved water molecule. A cluster of histidine and proline residues (His98-Pro99-His100-Pro101-His102) in kappa-casein binds to the C-terminal domain of the protein, where a neighboring conserved arginine residue (Arg97) is found to be important for stabilizing the binding pose. The catalytic site (including the catalytic water molecule) is stable in the starting conformation of the previously proposed general acid/base catalytic mechanism for 18 ns of molecular dynamics simulations.
|Keywords:||bovine chymosin, bovine kappa-casein , biochemistry, Physics, Biochemistry|
|Subjects:||Science > Physics|
|Department:||Faculty of Science > Physics|
|Depositing user:||Pure Administrator|
|Date Deposited:||16 Apr 2012 11:05|
|Last modified:||05 May 2016 00:22|