DB code: D00428

RLCP classification 1.13.30000.10 : Hydrolysis
CATH domain 2.40.10.10 : Thrombin, subunit H Catalytic domain
2.40.10.10 : Thrombin, subunit H Catalytic domain
E.C. 3.4.21.39
CSA
M-CSA
MACiE

CATH domain Related DB codes (homologues)
2.40.10.10 : Thrombin, subunit H M00139 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

Uniprot Enzyme Name
UniprotKB Protein name Synonyms RefSeq MEROPS Pfam
P23946 Chymase
EC 3.4.21.39
Alpha-chymase
Mast cell protease I
NP_001827.1 (Protein)
NM_001836.3 (DNA/RNA sequence)
S01.140 (Serine)
PF00089 (Trypsin)
[Graphical View]

KEGG enzyme name
chymase
mast cell protease I
skeletal muscle protease
skin chymotryptic proteinase
mast cell serine proteinase, chymase
skeletal muscle (SK) protease

UniprotKB: Accession Number Entry name Activity Subunit Subcellular location Cofactor
P23946 CMA1_HUMAN Preferential cleavage: Phe-|-Xaa > Tyr-|-Xaa > Trp-|-Xaa > Leu-|-Xaa. Secreted. Cytoplasmic granule. Note=Mast cell granules.

KEGG Pathways
Map code Pathways E.C.

Compound table
Substrates Products Intermediates
KEGG-id C00012 C00001 C00012 C00098 I00087 I00085 I00086
E.C.
Compound Peptide H2O Peptide Oligopeptide Peptidyl-tetrahedral intermediate Acyl-enzyme Tetrahedral intermediate
Type peptide/protein H2O peptide/protein amine group,carboxyl group,peptide/protein
ChEBI 15377
 15377
PubChem 22247451
 962
 22247451
 962
1kltA01 Unbound Unbound Unbound Unbound Unbound Transition-state-analogue:PMS
1pjpA01 Unbound Unbound Unbound Unbound Unbound Transition-state-analogue:ALA-ALA-PRO-PHM (chain I)
1nn6A01 Unbound Unbound Unbound Unbound Unbound Unbound
1kltA02 Unbound Unbound Unbound Unbound Unbound Unbound
1pjpA02 Unbound Unbound Unbound Unbound Unbound Unbound
1nn6A02 Unbound Unbound Unbound Unbound Unbound Unbound

Reference for Active-site residues
resource references E.C.
Swiss-prot;P23946

Active-site residues
PDB Catalytic residues Cofactor-binding residues Modified residues Main-chain involved in catalysis Comment
1kltA01 SER 195 GLY 193;SER 195 mutant C22S
1pjpA01 SER 195 GLY 193;SER 195
1nn6A01 SER 197 GLY 195;SER 197
1kltA02 HIS 57;ASP 102
1pjpA02 HIS 57;ASP 102
1nn6A02 HIS 60;ASP 104

References for Catalytic Mechanism
References Sections No. of steps in catalysis
[7]
p.14320-14321

References
[1]
Resource
Comments
Medline ID
PubMed ID 3893537
Journal Biochemistry
Year 1985
Volume 24
Pages 1831-41
Authors Harper JW, Hemmi K, Powers JC
Title Reaction of serine proteases with substituted isocoumarins: discovery of 3,4-dichloroisocoumarin, a new general mechanism based serine protease inhibitor.
Related PDB
Related UniProtKB
[2]
Resource
Comments
Medline ID
PubMed ID 3910097
Journal Biochemistry
Year 1985
Volume 24
Pages 7200-13
Authors Harper JW, Powers JC
Title Reaction of serine proteases with substituted 3-alkoxy-4-chloroisocoumarins and 3-alkoxy-7-amino-4-chloroisocoumarins: new reactive mechanism-based inhibitors.
Related PDB
Related UniProtKB
[3]
Resource
Comments
Medline ID
PubMed ID 1334431
Journal Biochemistry
Year 1992
Volume 31
Pages 12785-91
Authors Sreenivasan U, Axelsen PH
Title Buried water in homologous serine proteases.
Related PDB
Related UniProtKB
[4]
Resource
Comments
Medline ID
PubMed ID 7682557
Journal J Biol Chem
Year 1993
Volume 268
Pages 9023-34
Authors Sali A, Matsumoto R, McNeil HP, Karplus M, Stevens RL
Title Three-dimensional models of four mouse mast cell chymases. Identification of proteoglycan binding regions and protease-specific antigenic epitopes.
Related PDB
Related UniProtKB
[5]
Resource
Comments
Medline ID
PubMed ID 8226889
Journal J Biol Chem
Year 1993
Volume 268
Pages 23626-33
Authors Schechter NM, Jordan LM, James AM, Cooperman BS, Wang ZM, Rubin H
Title Reaction of human chymase with reactive site variants of alpha 1-antichymotrypsin. Modulation of inhibitor versus substrate properties.
Related PDB
Related UniProtKB
[6]
Resource
Comments
Medline ID
PubMed ID 8962677
Journal Biol Chem Hoppe Seyler
Year 1995
Volume 376
Pages 681-4
Authors Wang ZM, Rubin H, Schechter NM
Title Production of active recombinant human chymase from a construct containing the enterokinase cleavage site of trypsinogen in place of the native propeptide sequence.
Related PDB
Related UniProtKB
[7]
Resource
Comments X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS).
Medline ID 98062898
PubMed ID 9400368
Journal Biochemistry
Year 1997
Volume 36
Pages 14318-24
Authors McGrath ME, Mirzadegan T, Schmidt BF
Title Crystal structure of phenylmethanesulfonyl fluoride-treated human chymase at 1.9 A.
Related PDB 1klt
Related UniProtKB P23946
[8]
Resource
Comments
Medline ID
PubMed ID 9006943
Journal J Biol Chem
Year 1997
Volume 272
Pages 2963-8
Authors Sanker S, Chandrasekharan UM, Wilk D, Glynias MJ, Karnik SS, Husain A
Title Distinct multisite synergistic interactions determine substrate specificities of human chymase and rat chymase-1 for angiotensin II formation and degradation.
Related PDB
Related UniProtKB
[9]
Resource
Comments
Medline ID
PubMed ID 9305913
Journal J Biol Chem
Year 1997
Volume 272
Pages 24499-507
Authors Schechter NM, Plotnick M, Selwood T, Walter M, Rubin H
Title Diverse effects of pH on the inhibition of human chymase by serpins.
Related PDB
Related UniProtKB
[10]
Resource
Comments
Medline ID
PubMed ID 9216834
Journal J Med Chem
Year 1997
Volume 40
Pages 2156-63
Authors Niwata 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
Title Substituted 3-(phenylsulfonyl)-1-phenylimidazolidine-2,4-dione derivatives as novel nonpeptide inhibitors of human heart chymase.
Related PDB
Related UniProtKB
[11]
Resource
Comments
Medline ID
PubMed ID 10508424
Journal Biochemistry
Year 1999
Volume 38
Pages 12187-95
Authors Pejler G, Sadler JE
Title Mechanism by which heparin proteoglycan modulates mast cell chymase activity.
Related PDB
Related UniProtKB
[12]
Resource
Comments X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS).
Medline ID 99134396
PubMed ID 9931257
Journal J Mol Biol
Year 1999
Volume 286
Pages 163-73
Authors Pereira PJ, Wang ZM, Rubin H, Huber R, Bode W, Schechter NM, Strobl S
Title The 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 PDB 1pjp
Related UniProtKB P23946
[13]
Resource
Comments
Medline ID
PubMed ID 11209755
Journal Biol Chem
Year 2000
Volume 381
Pages 1203-14
Authors Estebanez-Perpina E, Fuentes-Prior P, Belorgey D, Braun M, Kiefersauer R, Maskos K, Huber R, Rubin H, Bode W
Title Crystal structure of the caspase activator human granzyme B, a proteinase highly specific for an Asp-P1 residue.
Related PDB
Related UniProtKB
[14]
Resource
Comments
Medline ID
PubMed ID 10698435
Journal Bioorg Med Chem Lett
Year 2000
Volume 10
Pages 199-201
Authors Hayashi Y, Iijima K, Katada J, Kiso Y
Title Structure-activity relationship studies of chloromethyl ketone derivatives for selective human chymase inhibitors.
Related PDB
Related UniProtKB
[15]
Resource
Comments
Medline ID
PubMed ID 11350059
Journal Biochem Biophys Res Commun
Year 2001
Volume 283
Pages 831-6
Authors Sakaguchi M, Yamamoto D, Takai S, Jin D, Taniguchi M, Baba K, Miyazaki M
Title Inhibitory mechanism of daphnodorins for human chymase.
Related PDB
Related UniProtKB
[16]
Resource
Comments
Medline ID
PubMed ID 11747453
Journal Biochemistry
Year 2001
Volume 40
Pages 15762-70
Authors Cooley J, Takayama TK, Shapiro SD, Schechter NM, Remold-O'Donnell E
Title The serpin MNEI inhibits elastase-like and chymotrypsin-like serine proteases through efficient reactions at two active sites.
Related PDB
Related UniProtKB
[17]
Resource
Comments
Medline ID
PubMed ID 12007614
Journal Biochim Biophys Acta
Year 2002
Volume 1596
Pages 346-56
Authors Muilenburg DJ, Raymond WW, Wolters PJ, Caughey GH
Title Lys40 but not Arg143 influences selectivity of angiotensin conversion by human alpha-chymase.
Related PDB
Related UniProtKB
[18]
Resource
Comments
Medline ID
PubMed ID 12614156
Journal Biochemistry
Year 2003
Volume 42
Pages 2616-24
Authors Reiling KK, Krucinski J, Miercke LJ, Raymond WW, Caughey GH, Stroud RM
Title Structure of human pro-chymase: a model for the activating transition of granule-associated proteases.
Related PDB
Related UniProtKB
[19]
Resource
Comments
Medline ID
PubMed ID 12815038
Journal J Biol Chem
Year 2003
Volume 278
Pages 34517-24
Authors Raymond WW, Ruggles SW, Craik CS, Caughey GH
Title Albumin is a substrate of human chymase. Prediction by combinatorial peptide screening and development of a selective inhibitor based on the albumin cleavage site.
Related PDB
Related UniProtKB

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).

Created Updated
2004-10-25 2011-02-18