Chymosin

Not to be confused with renin, an enzyme found in the appendix.
Chymosin
Crystal structure of bovine chymosin complex with the inhibitor CP-113972.[1]
Identifiers
EC number 3.4.23.4
CAS number 9001-98-3
Databases
IntEnz IntEnz view
BRENDA BRENDA entry
ExPASy NiceZyme view
KEGG KEGG entry
MetaCyc metabolic pathway
PRIAM profile
PDB structures RCSB PDB PDBe PDBsum
Gene Ontology AmiGO / EGO

Chymosin or rennin is an enzyme found in rennet. It is produced by cows in the lining of the abomasum (the fourth and final, chamber of the stomach). Chymosin is produced by gastric chief cells in infants to curdle the milk they ingest, allowing a longer residence in the bowels and better absorption. Bovine chymosin is now produced recombinantly in E. coli, Aspergillus niger var awamori, and K. lactis as alternative resource. The gene is found in humans (on chromosome 1), but it is not expressed.

Contents

Enzymatic reaction

Chymosin causes cleavage of a specific linkage — the peptide bond between 105 and 106, phenylalanine and methionine, in K-Casein, the native substrate of this enzyme.[2] Proceeding the uneven cleavage of kappa-casein, the opposite charges on the substrate can interact with the enzyme; histidines on the kappa-casein are attracted to glutamates and aspartate on chymosin.[2] When chymosin is not binding substrate, a beta-hairpin, sometimes referred to as "the flap," can hydrogen bond with the active site, therefore covering it and not allowing further binding of substrate.[1] If this reaction applies to milk, the specific linkage between the hydrophobic (para-casein) and hydrophilic (acidic glycopeptide) group of casein inside milk would be broken, since they are joined by phenylalanine and methionine. The hydrophobic group would unite and would form a 3D network to trap the aqueous phase of the milk. The resultant product is calcium phosphocaseinate. Due to this reaction, rennin is used to bring about the extensive precipitation and curd formation in cheese making.

Examples

Listed below are the cow Cym gene and corresponding human pseudogene:

Chymosin [Precursor] (B.taurus or C.dromedarius)
X-ray analysis of calf chymosin [3]
Identifiers
Symbol Cym
Alt. symbols CPC
Entrez 529879
PDB 4CMS
RefSeq NP_851337.1
UniProt Q9GK11
Other data
chymosin pseudogene (H.sapiens)
Identifiers
Symbol CYMP
Entrez 643160
HUGO 2588
OMIM 118943
RefSeq NR_003599
Other data
Locus Chr. 1 p13.3

References

  1. ^ a b PDB 1CZI; Groves MR, Dhanaraj V, Badasso M, Nugent P, Pitts JE, Hoover DJ, Blundell TL (October 1998). "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. 11 (10): 833–40. PMID 9862200. 
  2. ^ a b Gilliland GL, Oliva MT, Dill J (1991). "Functional implications of the three-dimensional structure of bovine chymosin". Adv. Exp. Med. Biol. 306: 23–37. PMID 1812710. 
  3. ^ PDB 4CMS; Newman M, Safro M, Frazao C, et al. (October 1991). "X-ray analyses of aspartic proteinases. IV. Structure and refinement at 2.2 A resolution of bovine chymosin". J. Mol. Biol. 221 (4): 1295–309. doi:10.1016/0022-2836(91)90934-X. PMID 1942052. 

Further reading

External links