EzCatDB: D00428
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DB codeD00428
RLCP classification1.13.30000.10 : Hydrolysis
CATH domainDomain 12.40.10.10 : Thrombin, subunit HCatalytic domain
Domain 22.40.10.10 : Thrombin, subunit HCatalytic domain
E.C.3.4.21.39

CATH domainRelated DB codes (homologues)
2.40.10.10 : Thrombin, subunit HM00139,D00214,M00167,D00426,M00133,D00429,D00430,D00431,D00432,D00433,D00434,D00435,M00227,M00209,D00194,D00197,D00211,D00212,D00216,M00212,D00224,D00497,M00217,M00216,D00528,D00848,D00850,D00851,D00852,D00855,M00152,M00155,M00157,M00181,M00315,M00316,M00317,M00348,M00349,T00074,T00410,T00411

Enzyme Name
UniProtKBKEGG

P23946
Protein nameChymasechymase
mast cell protease I
skeletal muscle protease
skin chymotryptic proteinase
mast cell serine proteinase, chymase
skeletal muscle (SK) protease
SynonymsEC 3.4.21.39
Alpha-chymase
Mast cell protease I
RefSeqNP_001827.1 (Protein)
NM_001836.3 (DNA/RNA sequence)
MEROPSS01.140 (Serine)
PfamPF00089 (Trypsin)
[Graphical view]


UniProtKB:Accession NumberP23946
Entry nameCMA1_HUMAN
ActivityPreferential cleavage: Phe-|-Xaa > Tyr-|-Xaa > Trp-|-Xaa > Leu-|-Xaa.
Subunit
Subcellular locationSecreted. Cytoplasmic granule. Note=Mast cell granules.
Cofactor

Compound table: links to PDB-related databases & PoSSuM

SubstratesProductsintermediates
KEGG-idC00012C00001C00012C00098I00087I00085I00086
CompoundPeptideH2OPeptideOligopeptidePeptidyl-tetrahedral intermediateAcyl-enzymeTetrahedral intermediate
Typepeptide/proteinH2Opeptide/proteinamine group,carboxyl group,peptide/protein


ChEBI
15377





PubChem
962
22247451





               
1kltA01Unbound UnboundUnboundUnboundUnboundTransition-state-analogue:PMS
1pjpA01Unbound UnboundUnboundUnboundUnboundTransition-state-analogue:ALA-ALA-PRO-PHM(chain I)
1nn6A01Unbound UnboundUnboundUnboundUnboundUnbound
1kltA02Unbound UnboundUnboundUnboundUnboundUnbound
1pjpA02Unbound UnboundUnboundUnboundUnboundUnbound
1nn6A02Unbound UnboundUnboundUnboundUnboundUnbound

Active-site residues
resource
Swiss-prot;P23946
pdbCatalytic residuesMain-chain involved in catalysiscomment
           
1kltA01SER 195
GLY 193;SER 195
mutant C22S
1pjpA01SER 195
GLY 193;SER 195
 
1nn6A01SER 197
GLY 195;SER 197
 
1kltA02HIS 57;ASP 102
 
 
1pjpA02HIS 57;ASP 102
 
 
1nn6A02HIS 60;ASP 104
 
 

References for Catalytic Mechanism
ReferencesSectionsNo. of steps in catalysis
[7]p.14320-14321

references
[1]
PubMed ID3893537
JournalBiochemistry
Year1985
Volume24
Pages1831-41
AuthorsHarper JW, Hemmi K, Powers JC
TitleReaction of serine proteases with substituted isocoumarins: discovery of 3,4-dichloroisocoumarin, a new general mechanism based serine protease inhibitor.
[2]
PubMed ID3910097
JournalBiochemistry
Year1985
Volume24
Pages7200-13
AuthorsHarper JW, Powers JC
TitleReaction of serine proteases with substituted 3-alkoxy-4-chloroisocoumarins and 3-alkoxy-7-amino-4-chloroisocoumarins: new reactive mechanism-based inhibitors.
[3]
PubMed ID1334431
JournalBiochemistry
Year1992
Volume31
Pages12785-91
AuthorsSreenivasan U, Axelsen PH
TitleBuried water in homologous serine proteases.
[4]
PubMed ID7682557
JournalJ Biol Chem
Year1993
Volume268
Pages9023-34
AuthorsSali A, Matsumoto R, McNeil HP, Karplus M, Stevens RL
TitleThree-dimensional models of four mouse mast cell chymases. Identification of proteoglycan binding regions and protease-specific antigenic epitopes.
[5]
PubMed ID8226889
JournalJ Biol Chem
Year1993
Volume268
Pages23626-33
AuthorsSchechter NM, Jordan LM, James AM, Cooperman BS, Wang ZM, Rubin H
TitleReaction of human chymase with reactive site variants of alpha 1-antichymotrypsin. Modulation of inhibitor versus substrate properties.
[6]
PubMed ID8962677
JournalBiol Chem Hoppe Seyler
Year1995
Volume376
Pages681-4
AuthorsWang ZM, Rubin H, Schechter NM
TitleProduction of active recombinant human chymase from a construct containing the enterokinase cleavage site of trypsinogen in place of the native propeptide sequence.
[7]
CommentsX-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS).
Medline ID98062898
PubMed ID9400368
JournalBiochemistry
Year1997
Volume36
Pages14318-24
AuthorsMcGrath ME, Mirzadegan T, Schmidt BF
TitleCrystal structure of phenylmethanesulfonyl fluoride-treated human chymase at 1.9 A.
Related PDB1klt
Related UniProtKBP23946
[8]
PubMed ID9006943
JournalJ Biol Chem
Year1997
Volume272
Pages2963-8
AuthorsSanker S, Chandrasekharan UM, Wilk D, Glynias MJ, Karnik SS, Husain A
TitleDistinct multisite synergistic interactions determine substrate specificities of human chymase and rat chymase-1 for angiotensin II formation and degradation.
[9]
PubMed ID9305913
JournalJ Biol Chem
Year1997
Volume272
Pages24499-507
AuthorsSchechter NM, Plotnick M, Selwood T, Walter M, Rubin H
TitleDiverse effects of pH on the inhibition of human chymase by serpins.
[10]
PubMed ID9216834
JournalJ Med Chem
Year1997
Volume40
Pages2156-63
AuthorsNiwata S, Fukami H, Sumida M, Ito A, Kakutani S, Saitoh M, Suzuki K, Imoto M, Shibata H, Imajo S, Kiso Y, Tanaka T, Nakazato H, Ishihara T, Takai S, Yamamoto D, Shiota N, Miyazaki M, Okunishi H, Kinoshita A, Urata H, Arakawa K
TitleSubstituted 3-(phenylsulfonyl)-1-phenylimidazolidine-2,4-dione derivatives as novel nonpeptide inhibitors of human heart chymase.
[11]
PubMed ID10508424
JournalBiochemistry
Year1999
Volume38
Pages12187-95
AuthorsPejler G, Sadler JE
TitleMechanism by which heparin proteoglycan modulates mast cell chymase activity.
[12]
CommentsX-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS).
Medline ID99134396
PubMed ID9931257
JournalJ Mol Biol
Year1999
Volume286
Pages163-73
AuthorsPereira PJ, Wang ZM, Rubin H, Huber R, Bode W, Schechter NM, Strobl S
TitleThe 2.2 A crystal structure of human chymase in complex with succinyl-Ala-Ala-Pro-Phe-chloromethylketone: structural explanation for its dipeptidyl carboxypeptidase specificity.
Related PDB1pjp
Related UniProtKBP23946
[13]
PubMed ID11209755
JournalBiol Chem
Year2000
Volume381
Pages1203-14
AuthorsEstebanez-Perpina E, Fuentes-Prior P, Belorgey D, Braun M, Kiefersauer R, Maskos K, Huber R, Rubin H, Bode W
TitleCrystal structure of the caspase activator human granzyme B, a proteinase highly specific for an Asp-P1 residue.
[14]
PubMed ID10698435
JournalBioorg Med Chem Lett
Year2000
Volume10
Pages199-201
AuthorsHayashi Y, Iijima K, Katada J, Kiso Y
TitleStructure-activity relationship studies of chloromethyl ketone derivatives for selective human chymase inhibitors.
[15]
PubMed ID11350059
JournalBiochem Biophys Res Commun
Year2001
Volume283
Pages831-6
AuthorsSakaguchi M, Yamamoto D, Takai S, Jin D, Taniguchi M, Baba K, Miyazaki M
TitleInhibitory mechanism of daphnodorins for human chymase.
[16]
PubMed ID11747453
JournalBiochemistry
Year2001
Volume40
Pages15762-70
AuthorsCooley J, Takayama TK, Shapiro SD, Schechter NM, Remold-O'Donnell E
TitleThe serpin MNEI inhibits elastase-like and chymotrypsin-like serine proteases through efficient reactions at two active sites.
[17]
PubMed ID12007614
JournalBiochim Biophys Acta
Year2002
Volume1596
Pages346-56
AuthorsMuilenburg DJ, Raymond WW, Wolters PJ, Caughey GH
TitleLys40 but not Arg143 influences selectivity of angiotensin conversion by human alpha-chymase.
[18]
PubMed ID12614156
JournalBiochemistry
Year2003
Volume42
Pages2616-24
AuthorsReiling KK, Krucinski J, Miercke LJ, Raymond WW, Caughey GH, Stroud RM
TitleStructure of human pro-chymase: a model for the activating transition of granule-associated proteases.
[19]
PubMed ID12815038
JournalJ Biol Chem
Year2003
Volume278
Pages34517-24
AuthorsRaymond WW, Ruggles SW, Craik CS, Caughey GH
TitleAlbumin is a substrate of human chymase. Prediction by combinatorial peptide screening and development of a selective inhibitor based on the albumin cleavage site.

comments
This enzyme belongs to the peptidase family-S1.
According to the literature [7], this enzyme has got a classical catalytic triad, composed of Ser/His/Asp, suggesting that it must have a similar catalytic mechanism to that of trypsin (D00197 in EzCatDB).

createdupdated
2004-10-252011-02-18


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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 2008)
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)
Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2012 - March 2013)
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