On the effect of mutations in bovine or camel chymosin on the thermodynamics of binding κ-caseins
Ansari, Samiul M. and Sørensen, Jesper and Schiøtt, Birgit and Palmer, David S. (2017) On the effect of mutations in bovine or camel chymosin on the thermodynamics of binding κ-caseins. Proteins: Structure, Function, and Bioinformatics. pp. 1-36. ISSN 0887-3585 (https://doi.org/10.1002/prot.25410)
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Abstract
Bovine and camel chymosins are aspartic proteases that are used in dairy food manufacturing. Both enzymes catalyse proteolysis of a milk protein, κ-casein, which helps to initiate milk coagulation. Surprisingly, camel chymosin shows a 70 % higher clotting activity than bovine chymosin for bovine milk, while exhibiting only 20 % of the unspecific proteolytic activity. By contrast, bovine chymosin is a poor coagulant for camel milk. Although both enzymes are marketed commercially, the disparity in their catalytic activity is not yet well understood at a molecular level, due in part to a lack of atomistic resolution data about the chymosin - κ-casein complexes. Here, we report computational alanine scanning calculations of all four chymosin - κ-casein complexes, allowing us to elucidate the influence that individual residues have on binding thermodynamics. Of the 12 sequence di erences in the binding sites of bovine and camel chymosin, eight are shown to be particularly important for understanding di erences in the binding thermodynamics (Asp112Glu, Lys221Val, Gln242Arg, Gln278Lys. Glu290Asp, His292Asn, Gln294Glu, and Lys295Leu. Residue in bovine chymosin written first). The relative binding free energies of single-point mutants of chymosin are calculated using the molecular mechanics three dimensional reference interaction site model (MM-3DRISM). Visualisation of the solvent density functions calculated by 3DRISM reveals the di erence in solvation of the binding sites of chymosin mutants.
ORCID iDs
Ansari, Samiul M. ORCID: https://orcid.org/0000-0003-1066-1112, Sørensen, Jesper, Schiøtt, Birgit and Palmer, David S. ORCID: https://orcid.org/0000-0003-4356-9144;-
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Item type: Article ID code: 62184 Dates: DateEvent30 October 2017Published30 October 2017Published Online27 October 2017AcceptedNotes: This is the peer reviewed version of the following article: Ansari, SM, Sørensen, J, Schiøtt, B & Palmer, DS 2017, 'On the effect of mutations in bovine or camel chymosin on the thermodynamics of binding κ-caseins' Proteins: Structure, Function, and Bioinformatics, pp. 1-36., which has been published in final form at https://doi.org/10.1002/prot.25410. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving. Subjects: Medicine Department: Faculty of Science > Pure and Applied Chemistry Depositing user: Pure Administrator Date deposited: 31 Oct 2017 01:18 Last modified: 03 Oct 2024 00:27 Related URLs: URI: https://strathprints.strath.ac.uk/id/eprint/62184