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Restrained molecular dynamics study of the interaction between bovine κ-casein peptide 98–111 and bovine chymosin and porcine pepsin

Published online by Cambridge University Press:  01 June 2009

Jeffrey E. Plowman  and
Lawrence K. Creamer
Jeffrey E. Plowman
Affiliation:
New Zealand Dairy Research Institute, Palmerston North, New Zealand
Lawrence K. Creamer
Affiliation:
New Zealand Dairy Research Institute, Palmerston North, New Zealand
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Summary

The cleavage of bovine κ-casein at the Phe105–Met106* bond by chymosin or pepsin is the first stage in casein micelle coagulation and casein digestion. The nature of the interaction of the peptide His98–Pro–His–Pro–His–Leu–Ser–Phe105–Met–Ala–Ile–Pro-Pro-Lys111 with chymosin and porcine pepsin was investigated using molecular modelling and energy minimization techniques. This study verified and extended a proposed model that electrostatic binding (involving His98, His100, His102 and Lys111 or Lys112) at either end of the active site cleft of chymosin is important for the positioning of residues 103–108 in the cleft. The peptide conformation remained unchanged in going from solution to binding into the active site cleft, with the exception that optimum binding of substrate to chymosin required the isomerization of the His98–Pro99 peptide bond from the trans to the cis conformation. The study also identified an acidic region in porcine pepsin that is in a position to form strong electrostatic interactions with the histidines at the N-terminus of the peptide.

Type
Original Articles
Information
Journal of Dairy Research , Volume 62 , Issue 3 , August 1995 , pp. 451 - 467
Copyright
Copyright © Proprietors of Journal of Dairy Research 1995

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