Chymosin

Not to be confused with renin, an enzyme found in the kidney.

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
Search PMC articles PubMed articles

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.

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.^{[citation needed]} 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

• Foltmann B (1966). "A review on prorennin and rennin". C R Trav Lab Carlsberg 35 (8): 143–231. PMID 5330666. 
•  Harris TJ, Lowe PA, Lyons A, Thomas PG, Eaton MA, Millican TA, Patel TP, Bose CC, Carey NH, Doel MT (April 1982). "Molecular cloning and nucleotide sequence of cDNA coding for calf preprochymosin". Nucleic Acids Res. 10 (7): 2177–87. doi:10.1093/nar/10.7.2177. PMC 320601. PMID 6283469. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=320601. 
• Visser S, Slangen CJ, van Rooijen PJ (June 1987). "Peptide substrates for chymosin (rennin). Interaction sites in kappa-casein-related sequences located outside the (103-108)-hexapeptide region that fits into the enzyme's active-site cleft". Biochem. J. 244 (3): 553–8. PMC 1148031. PMID 3128264. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1148031. 

External links

• The MEROPS online database for peptidases and their inhibitors: A01.006