DB code: D00423

RLCP classification 1.13.200.966 : Hydrolysis
CATH domain 2.40.70.10 : Cathepsin D, subunit A; domain 1 Catalytic domain
2.40.70.10 : Cathepsin D, subunit A; domain 1 Catalytic domain
E.C. 3.4.23.4
CSA 1cms
M-CSA 1cms
MACiE

CATH domain Related DB codes (homologues)
2.40.70.10 : Cathepsin D, subunit A; domain 1 D00471 D00436 D00438 D00439 D00440 D00441 D00442 D00443 D00437 D00444 D00445 D00484 M00206 M00166 D00231 D00529

Uniprot Enzyme Name
UniprotKB Protein name Synonyms RefSeq MEROPS Pfam
P00794 Chymosin
EC 3.4.23.4
Preprorennin
NP_851337.1 (Protein)
NM_180994.2 (DNA/RNA sequence)
A01.006 (Aspartic)
PF07966 (A1_Propeptide)
PF00026 (Asp)
[Graphical View]

KEGG enzyme name
chymosin
rennin (but this should be avoided since it leads to confusion withrenin)

UniprotKB: Accession Number Entry name Activity Subunit Subcellular location Cofactor
P00794 CHYM_BOVIN Broad specificity similar to that of pepsin A. Clots milk by cleavage of a single 105-Ser-Phe-|-Met-Ala-108 bond in kappa-chain of casein. Monomer.

KEGG Pathways
Map code Pathways E.C.

Compound table
Substrates Products Intermediates
KEGG-id C00017 C00012 C01483 C00001 C00017 C00012 I00136
E.C.
Compound Protein Peptide Casein K H2O Protein Peptide Amino-diol-tetrahedral intermediate
Type peptide/protein peptide/protein peptide/protein H2O peptide/protein peptide/protein
ChEBI 74101
15377
PubChem 439506
22247451
962
1cmsA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound
1cziE01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Transition-state-analogue:PRO-PHI-SMC-NOR
3cmsA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound
4cmsA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound
1cmsA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound
1cziE02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound
3cmsA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound
4cmsA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound

Reference for Active-site residues
resource references E.C.
Swiss-prot;P00794

Active-site residues
PDB Catalytic residues Cofactor-binding residues Modified residues Main-chain involved in catalysis Comment
1cmsA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASP 34
1cziE01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASP 32
3cmsA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASP 32
4cmsA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASP 32
1cmsA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASP 216
1cziE02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASP 215
3cmsA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASP 215
4cmsA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASP 215

References for Catalytic Mechanism
References Sections No. of steps in catalysis
[9]
p.1304-1305

References
[1]
Resource
Comments ACTIVE SITE PEPTIDES OF CHYMOSIN B.
Medline ID 75060332
PubMed ID 4612029
Journal J Biochem (Tokyo)
Year 1974
Volume 76
Pages 467-74
Authors Chang WJ, Takahashi K
Title The structure and function of acid proteases. III. Isolation and characterization of the active-site peptides from bovine rennin.
Related PDB
Related UniProtKB P00794
[2]
Resource
Comments
Medline ID
PubMed ID 2501781
Journal Protein Eng
Year 1989
Volume 2
Pages 563-9
Authors Suzuki J, Sasaki K, Sasao Y, Hamu A, Kawasaki H, Nishiyama M, Horinouchi S, Beppu T
Title Alteration of catalytic properties of chymosin by site-directed mutagenesis.
Related PDB
Related UniProtKB
[3]
Resource
Comments X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF MUTANT.
Medline ID 91104895
PubMed ID 2271625
Journal Biochemistry
Year 1990
Volume 29
Pages 9863-71
Authors Strop P, Sedlacek J, Stys J, Kaderabkova Z, Blaha I, Pavlickova L, Pohl J, Fabry M, Kostka V, Newman M, et al
Title Engineering enzyme subsite specificity: preparation, kinetic characterization, and X-ray analysis at 2.0-A resolution of Val111Phe site-mutated calf chymosin.
Related PDB 3cms
Related UniProtKB P00794
[4]
Resource
Comments
Medline ID
PubMed ID 2217134
Journal Protein Eng
Year 1990
Volume 3
Pages 605-9
Authors Mantafounis D, Pitts J
Title Protein engineering of chymosin; modification of the optimum pH of enzyme catalysis.
Related PDB
Related UniProtKB
[5]
Resource
Comments X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS).
Medline ID 91017501
PubMed ID 2217166
Journal Proteins
Year 1990
Volume 8
Pages 82-101
Authors Gilliland GL, Winborne EL, Nachman J, Wlodawer A
Title The three-dimensional structure of recombinant bovine chymosin at 2.3 A resolution.
Related PDB 1cms
Related UniProtKB P00794
[6]
Resource
Comments
Medline ID
PubMed ID 1812745
Journal Adv Exp Med Biol
Year 1991
Volume 306
Pages 47-61
Authors Cooper JB, Newman MP
Title X-ray structural studies of mammalian aspartic proteinases.
Related PDB
Related UniProtKB
[7]
Resource
Comments
Medline ID
PubMed ID 1812710
Journal Adv Exp Med Biol
Year 1991
Volume 306
Pages 23-37
Authors Gilliland GL, Oliva MT, Dill J
Title Functional implications of the three-dimensional structure of bovine chymosin.
Related PDB
Related UniProtKB
[8]
Resource
Comments
Medline ID
PubMed ID 1820027
Journal Biomed Biochim Acta
Year 1991
Volume 50
Pages S102-5
Authors Abdel Malak CA, Lavrenova GI
Title Chymosin-catalyzed peptide synthesis.
Related PDB
Related UniProtKB
[9]
Resource
Comments X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS).
Medline ID 92046065
PubMed ID 1942052
Journal J Mol Biol
Year 1991
Volume 221
Pages 1295-309
Authors Newman M, Safro M, Frazao C, Khan G, Zdanov A, Tickle IJ, Blundell TL, Andreeva N
Title X-ray analyses of aspartic proteinases. IV. Structure and refinement at 2.2 A resolution of bovine chymosin.
Related PDB 4cms
Related UniProtKB P00794
[10]
Resource
Comments
Medline ID
PubMed ID 1575726
Journal Biochem Biophys Res Commun
Year 1992
Volume 184
Pages 1074-81
Authors Andreeva N, Dill J, Gilliland GL
Title Can enzymes adopt a self-inhibited form? Results of x-ray crystallographic studies of chymosin.
Related PDB
Related UniProtKB
[11]
Resource
Comments MUTAGENESIS OF CYS-308 AND CYS-341.
Medline ID 92412108
PubMed ID 1530626
Journal Biochem Biophys Res Commun
Year 1992
Volume 187
Pages 692-6
Authors Huang K, Zhang Z, Liu N, Zhang Y, Zhang G, Yang K
Title Functional implication of disulfide bond, Cys250 -Cys283, in bovine chymosin.
Related PDB
Related UniProtKB P00794
[12]
Resource
Comments
Medline ID
PubMed ID 1603805
Journal Proteins
Year 1992
Volume 12
Pages 158-70
Authors Sali A, Veerapandian B, Cooper JB, Moss DS, Hofmann T, Blundell TL
Title Domain flexibility in aspartic proteinases.
Related PDB
Related UniProtKB
[13]
Resource
Comments
Medline ID
PubMed ID 8540386
Journal Adv Exp Med Biol
Year 1995
Volume 362
Pages 95-9
Authors Dhanaraj RR, Pitts JE, Nugent P, Orprayoon P, Cooper JB, Blundell TL, Uusitalo J, Penttila M
Title Protein engineering of surface loops: preliminary X-ray analysis of the CHY155-165RHI mutant.
Related PDB
Related UniProtKB
[14]
Resource
Comments
Medline ID
PubMed ID 7593830
Journal J Dairy Res
Year 1995
Volume 62
Pages 451-67
Authors Plowman JE, Creamer LK
Title Restrained molecular dynamics study of the interaction between bovine kappa-casein peptide 98-111 and bovine chymosin and porcine pepsin.
Related PDB
Related UniProtKB
[15]
Resource
Comments
Medline ID
PubMed ID 8566230
Journal FEBS Lett
Year 1996
Volume 379
Pages 60-2
Authors Gustchina E, Rumsh L, Ginodman L, Majer P, Andreeva N
Title Post X-ray crystallographic studies of chymosin: the existence of two structural forms and the regulation of activity by the interaction with the histidine-proline cluster of kappa-casein.
Related PDB
Related UniProtKB
[16]
Resource
Comments
Medline ID
PubMed ID 8931128
Journal Protein Eng
Year 1996
Volume 9
Pages 885-93
Authors Nugent PG, Albert A, Orprayoon P, Wilsher J, Pitts JE, Blundell TL, Dhanaraj V
Title Protein engineering loops in aspartic proteinases: site-directed mutagenesis, biochemical characterization and X-ray analysis of chymosin with a replaced loop from rhizopuspepsin.
Related PDB
Related UniProtKB
[17]
Resource
Comments
Medline ID
PubMed ID 9434118
Journal Biochim Biophys Acta
Year 1997
Volume 1343
Pages 278-86
Authors Zhang Y, Li H, Wu H, Don Y, Liu N, Yang K
Title Functional implications of disulfide bond, Cys45-Cys50, in recombinant prochymosin.
Related PDB
Related UniProtKB
[18]
Resource
Comments
Medline ID
PubMed ID 9464563
Journal Protein Eng
Year 1997
Volume 10
Pages 991-7
Authors Williams MG, Wilsher J, Nugent P, Mills A, Dhanaraj V, Fabry M, Sedlacek J, Uusitalo JM, Penttila ME, Pitts JE, Blundell TL
Title Mutagenesis, biochemical characterization and X-ray structural analysis of point mutants of bovine chymosin.
Related PDB
Related UniProtKB
[19]
Resource
Comments
Medline ID
PubMed ID 9561215
Journal Adv Exp Med Biol
Year 1998
Volume 436
Pages 169-77
Authors Albert A, Blundell TL, Dhanaraj V, Donate LE, Groves M, Guruprasad K, Nugent PG, Orprayoon P, Pitts JE, Rufino S, Srinivasan N, Williams M, Wilsher J
Title Protein engineering aspartic proteinases. Site-directed mutagenesis, biochemical characterisation, and X-ray analysis of chymosins with substituted single amino acid substitutions and loop replacements.
Related PDB
Related UniProtKB
[20]
Resource
Comments
Medline ID
PubMed ID 9561216
Journal Adv Exp Med Biol
Year 1998
Volume 436
Pages 179-84
Authors Gustchina EA, Majer P, Rumsh LD, Ginodman LM, Andreeva NS
Title Post X-ray crystallographic studies of chymosin specificity. The role of histidine-proline cluster of kappa-casein in catalytic reactions.
Related PDB
Related UniProtKB
[21]
Resource
Comments
Medline ID
PubMed ID 9794784
Journal Biochem J
Year 1998
Volume 335
Pages 481-90
Authors Richter C, Tanaka T, Yada RY
Title Mechanism of activation of the gastric aspartic proteinases: pepsinogen, progastricsin and prochymosin.
Related PDB
Related UniProtKB
[22]
Resource
Comments X-ray crystallography
Medline ID
PubMed ID 9862200
Journal Protein Eng
Year 1998
Volume 11
Pages 833-40
Authors Groves MR, Dhanaraj V, Badasso M, Nugent P, Pitts JE, Hoover DJ, Blundell TL
Title 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.
Related PDB 1czi
Related UniProtKB
[23]
Resource
Comments
Medline ID
PubMed ID 11015192
Journal Biochemistry
Year 2000
Volume 39
Pages 12140-8
Authors Chen H, Zhang G, Zhang Y, Dong Y, Yang K
Title Functional implications of disulfide bond, Cys206-Cys210, in recombinant prochymosin (chymosin).
Related PDB
Related UniProtKB
[24]
Resource
Comments
Medline ID
PubMed ID 11298755
Journal Eur J Biochem
Year 2001
Volume 268
Pages 2362-8
Authors Francky A, Francky BM, Strukelj B, Gruden K, Ritonja A, Krizaj I, Kregar I, Pain RH, Pungercar J
Title A basic residue at position 36p of the propeptide is not essential for the correct folding and subsequent autocatalytic activation of prochymosin.
Related PDB
Related UniProtKB
[25]
Resource
Comments
Medline ID
PubMed ID 15568804
Journal Biochemistry
Year 2004
Volume 43
Pages 15122-30
Authors Kageyama T
Title Role of S'1 loop residues in the substrate specificities of pepsin A and chymosin.
Related PDB
Related UniProtKB

Comments
This enzyme belongs to the peptidase family-A1.
This enzyme has got a catalytic dyad, composed of two aspartic acid residues, which are conserved among other aspartate proteases such as pepsin (D00436 in EzCatDB). Thus, its catalytic mechanism must be similar to those.

Created Updated
2003-07-17 2012-06-27