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Catalytic Site Atlas

CSA LITERATURE entry for 1cms

E.C. namechymosin
SpeciesBos taurus (Bovine)
E.C. Number (IntEnz)
CSA Homologues of 1cmsThere are 301 Homologs
CSA Entries With UniProtID P00794
CSA Entries With EC Number
PDBe Entry 1cms
PDBSum Entry 1cms
MACiE Entry 1cms

Literature Report

IntroductionBovine chymosin is a aspartic protease which has historically been use in cheese manufacturing as a milk clotting initiator. The active bovine enzyme is formed by proteolytic cleavage of a 42 residue N terminal pro-peptide from the zymogen in the acidic environment of the bovine stomach.
MechansimGenerally, a mechanism of hydrolysis involving two Asp residues, with nucleophilic attack on the peptide carbonyl backbone via a catalytic water molecule has been accepted. However, two detailed descriptions of this mechanism exist.
Crystallographic data and neutron diffraction studies suggest that the scissile bond carbonyl is protonated by Asp 34 and concurrently attacked by the hydrolytic water molecule which is activated by the deprotonated Asp216. Kinetic data and computer models implicate a mechanism which involves the formation of low energy hydrogen bonds between Asp34 and Asp216 with the rearrangement of protons throughout a ten membered cyclic intermediate.

Catalytic Sites for 1cms

Literature References

Palmer DS
Bovine chymosin: a computational study of recognition and binding of bovine kappa-casein.
Biochemistry 2010 49 2563-2573
PubMed: 20155951
Gilliland GL
The three-dimensional structure of recombinant bovine chymosin at 2.3 A resolution.
Proteins 1990 8 82-101
PubMed: 2217166
Groves MR
A 2.3 A resolution structure of chymosin complexed with a reduced bond inhibitor shows that the active site beta-hairpin flap is rearranged when compared with the native crystal structure.
Protein Eng 1998 11 833-840
PubMed: 9862200
Andreeva NS
Analysis of crystal structures of aspartic proteinases: on the role of amino acid residues adjacent to the catalytic site of pepsin-like enzymes.
Protein Sci 2001 10 2439-2450
PubMed: 11714911