Bovine chymosin: a computational study of recognition and binding of bovine kappa-casein

D. S. Palmer, A. U. Christensen, J. Sørensen, L. Celik, K. B. Qvist, B. Schiøtt

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

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.
LanguageUndefined/Unknown
Pages2563-2573
Number of pages11
JournalBiochemistry
Volume49
Issue number11
DOIs
Publication statusPublished - 1 Mar 2010

Keywords

  • bovine chymosin
  • bovine kappa-casein
  • biochemistry

Cite this

Palmer, D. S., Christensen, A. U., Sørensen, J., Celik, L., Qvist, K. B., & Schiøtt, B. (2010). Bovine chymosin: a computational study of recognition and binding of bovine kappa-casein. Biochemistry, 49(11), 2563-2573. https://doi.org/10.1021/bi902193u
Palmer, D. S. ; Christensen, A. U. ; Sørensen, J. ; Celik, L. ; Qvist, K. B. ; Schiøtt, B. / Bovine chymosin: a computational study of recognition and binding of bovine kappa-casein. In: Biochemistry. 2010 ; Vol. 49, No. 11. pp. 2563-2573.
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abstract = "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.",
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Palmer, DS, Christensen, AU, Sørensen, J, Celik, L, Qvist, KB & Schiøtt, B 2010, 'Bovine chymosin: a computational study of recognition and binding of bovine kappa-casein' Biochemistry, vol. 49, no. 11, pp. 2563-2573. https://doi.org/10.1021/bi902193u

Bovine chymosin: a computational study of recognition and binding of bovine kappa-casein. / Palmer, D. S.; Christensen, A. U.; Sørensen, J.; Celik, L.; Qvist, K. B.; Schiøtt, B.

In: Biochemistry, Vol. 49, No. 11, 01.03.2010, p. 2563-2573.

Research output: Contribution to journalArticle

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T1 - Bovine chymosin: a computational study of recognition and binding of bovine kappa-casein

AU - Palmer, D. S.

AU - Christensen, A. U.

AU - Sørensen, J.

AU - Celik, L.

AU - Qvist, K. B.

AU - Schiøtt, B.

PY - 2010/3/1

Y1 - 2010/3/1

N2 - 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.

AB - 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.

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Palmer DS, Christensen AU, Sørensen J, Celik L, Qvist KB, Schiøtt B. Bovine chymosin: a computational study of recognition and binding of bovine kappa-casein. Biochemistry. 2010 Mar 1;49(11):2563-2573. https://doi.org/10.1021/bi902193u