EzCatDB: D00423

DB codeD00423
RLCP classification1.13.200.966
CATH domainDomain 12.40.70.10Catalytic domain
Domain 22.40.70.10Catalytic domain
E.C.3.4.23.4
CSA1cms

CATH domainRelated DB codes (homologues)
2.40.70.10D00471,D00436,D00438,D00439,D00440,D00441,D00442,D00443,D00437,D00444,D00445,D00484,M00206,M00166,D00231,D00529

Enzyme Name
Swiss-protKEGG

P00794
Protein nameChymosinchymosin
rennin (but this should be avoided since it leads to confusion withrenin)
SynonymsEC 3.4.23.4
Preprorennin


Swiss-prot:Accession NumberP00794
Entry nameCHYM_BOVIN
ActivityBroad 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.
SubunitMonomer.
Subcellular location
Cofactor


SubstratesProductsintermediates
KEGG-idC00017C00012C01483C00001C00017C00012I00136
CompoundProteinPeptideCasein KH2OProteinPeptideAmino-diol-tetrahedral intermediate
Typepeptide/proteinpeptide/proteinpeptide/proteinH2Opeptide/proteinpeptide/protein
1cmsA01UnboundUnboundUnbound
UnboundUnboundUnbound
1cziE01UnboundUnboundUnbound
UnboundUnboundTransition-state-analogue:PRO-PHI-SMC-NOR
3cmsA01UnboundUnboundUnbound
UnboundUnboundUnbound
4cmsA01UnboundUnboundUnbound
UnboundUnboundUnbound
1cmsA02UnboundUnboundUnbound
UnboundUnboundUnbound
1cziE02UnboundUnboundUnbound
UnboundUnboundUnbound
3cmsA02UnboundUnboundUnbound
UnboundUnboundUnbound
4cmsA02UnboundUnboundUnbound
UnboundUnboundUnbound

Active-site residues
resource
Swiss-prot;P00794
pdbCatalytic residues
1cmsA01ASP 34
1cziE01ASP 32
3cmsA01ASP 32
4cmsA01ASP 32
1cmsA02ASP 216
1cziE02ASP 215
3cmsA02ASP 215
4cmsA02ASP 215

References for Catalytic Mechanism
ReferencesSectionsNo. of steps in catalysis
[9]p.1304-1305

references
[1]
CommentsACTIVE SITE PEPTIDES OF CHYMOSIN B.
Medline ID75060332
PubMed ID4612029
JournalJ Biochem (Tokyo)
Year1974
Volume76
Pages467-74
AuthorsChang WJ, Takahashi K
TitleThe structure and function of acid proteases. III. Isolation and characterization of the active-site peptides from bovine rennin.
Related Swiss-protP00794
[2]
PubMed ID2501781
JournalProtein Eng
Year1989
Volume2
Pages563-9
AuthorsSuzuki J, Sasaki K, Sasao Y, Hamu A, Kawasaki H, Nishiyama M, Horinouchi S, Beppu T
TitleAlteration of catalytic properties of chymosin by site-directed mutagenesis.
[3]
CommentsX-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF MUTANT.
Medline ID91104895
PubMed ID2271625
JournalBiochemistry
Year1990
Volume29
Pages9863-71
AuthorsStrop P, Sedlacek J, Stys J, Kaderabkova Z, Blaha I, Pavlickova L, Pohl J, Fabry M, Kostka V, Newman M, et al
TitleEngineering enzyme subsite specificity: preparation, kinetic characterization, and X-ray analysis at 2.0-A resolution of Val111Phe site-mutated calf chymosin.
Related PDB3cms
Related Swiss-protP00794
[4]
PubMed ID2217134
JournalProtein Eng
Year1990
Volume3
Pages605-9
AuthorsMantafounis D, Pitts J
TitleProtein engineering of chymosin; modification of the optimum pH of enzyme catalysis.
[5]
CommentsX-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS).
Medline ID91017501
PubMed ID2217166
JournalProteins
Year1990
Volume8
Pages82-101
AuthorsGilliland GL, Winborne EL, Nachman J, Wlodawer A
TitleThe three-dimensional structure of recombinant bovine chymosin at 2.3 A resolution.
Related PDB1cms
Related Swiss-protP00794
[6]
PubMed ID1812745
JournalAdv Exp Med Biol
Year1991
Volume306
Pages47-61
AuthorsCooper JB, Newman MP
TitleX-ray structural studies of mammalian aspartic proteinases.
[7]
PubMed ID1812710
JournalAdv Exp Med Biol
Year1991
Volume306
Pages23-37
AuthorsGilliland GL, Oliva MT, Dill J
TitleFunctional implications of the three-dimensional structure of bovine chymosin.
[8]
PubMed ID1820027
JournalBiomed Biochim Acta
Year1991
Volume50
PagesS102-5
AuthorsAbdel Malak CA, Lavrenova GI
TitleChymosin-catalyzed peptide synthesis.
[9]
CommentsX-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS).
Medline ID92046065
PubMed ID1942052
JournalJ Mol Biol
Year1991
Volume221
Pages1295-309
AuthorsNewman M, Safro M, Frazao C, Khan G, Zdanov A, Tickle IJ, Blundell TL, Andreeva N
TitleX-ray analyses of aspartic proteinases. IV. Structure and refinement at 2.2 A resolution of bovine chymosin.
Related PDB4cms
Related Swiss-protP00794
[10]
PubMed ID1575726
JournalBiochem Biophys Res Commun
Year1992
Volume184
Pages1074-81
AuthorsAndreeva N, Dill J, Gilliland GL
TitleCan enzymes adopt a self-inhibited form? Results of x-ray crystallographic studies of chymosin.
[11]
CommentsMUTAGENESIS OF CYS-308 AND CYS-341.
Medline ID92412108
PubMed ID1530626
JournalBiochem Biophys Res Commun
Year1992
Volume187
Pages692-6
AuthorsHuang K, Zhang Z, Liu N, Zhang Y, Zhang G, Yang K
TitleFunctional implication of disulfide bond, Cys250 -Cys283, in bovine chymosin.
Related Swiss-protP00794
[12]
PubMed ID1603805
JournalProteins
Year1992
Volume12
Pages158-70
AuthorsSali A, Veerapandian B, Cooper JB, Moss DS, Hofmann T, Blundell TL
TitleDomain flexibility in aspartic proteinases.
[13]
PubMed ID8540386
JournalAdv Exp Med Biol
Year1995
Volume362
Pages95-9
AuthorsDhanaraj RR, Pitts JE, Nugent P, Orprayoon P, Cooper JB, Blundell TL, Uusitalo J, Penttila M
TitleProtein engineering of surface loops: preliminary X-ray analysis of the CHY155-165RHI mutant.
[14]
PubMed ID7593830
JournalJ Dairy Res
Year1995
Volume62
Pages451-67
AuthorsPlowman JE, Creamer LK
TitleRestrained molecular dynamics study of the interaction between bovine kappa-casein peptide 98-111 and bovine chymosin and porcine pepsin.
[15]
PubMed ID8566230
JournalFEBS Lett
Year1996
Volume379
Pages60-2
AuthorsGustchina E, Rumsh L, Ginodman L, Majer P, Andreeva N
TitlePost 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.
[16]
PubMed ID8931128
JournalProtein Eng
Year1996
Volume9
Pages885-93
AuthorsNugent PG, Albert A, Orprayoon P, Wilsher J, Pitts JE, Blundell TL, Dhanaraj V
TitleProtein engineering loops in aspartic proteinases: site-directed mutagenesis, biochemical characterization and X-ray analysis of chymosin with a replaced loop from rhizopuspepsin.
[17]
PubMed ID9434118
JournalBiochim Biophys Acta
Year1997
Volume1343
Pages278-86
AuthorsZhang Y, Li H, Wu H, Don Y, Liu N, Yang K
TitleFunctional implications of disulfide bond, Cys45-Cys50, in recombinant prochymosin.
[18]
PubMed ID9464563
JournalProtein Eng
Year1997
Volume10
Pages991-7
AuthorsWilliams MG, Wilsher J, Nugent P, Mills A, Dhanaraj V, Fabry M, Sedlacek J, Uusitalo JM, Penttila ME, Pitts JE, Blundell TL
TitleMutagenesis, biochemical characterization and X-ray structural analysis of point mutants of bovine chymosin.
[19]
PubMed ID9561215
JournalAdv Exp Med Biol
Year1998
Volume436
Pages169-77
AuthorsAlbert 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
TitleProtein engineering aspartic proteinases. Site-directed mutagenesis, biochemical characterisation, and X-ray analysis of chymosins with substituted single amino acid substitutions and loop replacements.
[20]
PubMed ID9561216
JournalAdv Exp Med Biol
Year1998
Volume436
Pages179-84
AuthorsGustchina EA, Majer P, Rumsh LD, Ginodman LM, Andreeva NS
TitlePost X-ray crystallographic studies of chymosin specificity. The role of histidine-proline cluster of kappa-casein in catalytic reactions.
[21]
PubMed ID9794784
JournalBiochem J
Year1998
Volume335
Pages481-90
AuthorsRichter C, Tanaka T, Yada RY
TitleMechanism of activation of the gastric aspartic proteinases: pepsinogen, progastricsin and prochymosin.
[22]
CommentsX-ray crystallography
PubMed ID9862200
JournalProtein Eng
Year1998
Volume11
Pages833-40
AuthorsGroves MR, Dhanaraj V, Badasso M, Nugent P, Pitts JE, Hoover DJ, Blundell TL
TitleA 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 PDB1czi
[23]
PubMed ID11015192
JournalBiochemistry
Year2000
Volume39
Pages12140-8
AuthorsChen H, Zhang G, Zhang Y, Dong Y, Yang K
TitleFunctional implications of disulfide bond, Cys206-Cys210, in recombinant prochymosin (chymosin).
[24]
PubMed ID11298755
JournalEur J Biochem
Year2001
Volume268
Pages2362-8
AuthorsFrancky A, Francky BM, Strukelj B, Gruden K, Ritonja A, Krizaj I, Kregar I, Pain RH, Pungercar J
TitleA basic residue at position 36p of the propeptide is not essential for the correct folding and subsequent autocatalytic activation of prochymosin.
[25]
PubMed ID15568804
JournalBiochemistry
Year2004
Volume43
Pages15122-30
AuthorsKageyama T
TitleRole of S'1 loop residues in the substrate specificities of pepsin A and chymosin.

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.

createdupdated
2003-07-172012-06-27


Copyright: Nozomi Nagano, JST & CBRC-AIST
Funded by PRESTO/Japan Science and Technology Corporation (JST) (December 2001 - November 2004)
Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2005 - March 2006)
Funded by Grant-in-Aid for Scientific Research (B)/Japan Society for the Promotion of Science (JSPS) (April 2005 - March 2008)
Funded by BIRD/Japan Science and Technology Corporation (JST) (September 2005 - September 2010)
Funded by BIRD/Japan Science and Technology Corporation (JST) (October 2007 - September 2010)
Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2011 - March 2012)

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