S00374
type: Enzyme
rlcp: p10
cath: Rossmann fold
ec: https://purl.uniprot.org/enzyme/3.4.16.6
csa: 1bcr
macie: M0005
uniprot: P08819
kegg enzyme: carboxypeptidase D
kegg enzyme: cereal serine carboxypeptidase II
kegg enzyme: Saccharomyces cerevisiae KEX1 gene product
kegg enzyme: carboxypeptidase Kex1
kegg enzyme: gene KEX1 serine carboxypeptidase
kegg enzyme: KEX1 carboxypeptidase
kegg enzyme: KEX1 proteinase
kegg enzyme: KEX1DELTAp
kegg enzyme: CPDW-II
kegg enzyme: serine carboxypeptidase
kegg enzyme: Phaseolus proteinase
kegg substrate: Peptide
kegg substrate: H2O
kegg product: Peptide
kegg product: L-Arginine
kegg product: L-Lysine
kegg intermediate: Peptidyl-tetrahedral intermediate
kegg intermediate: Acyl-enzyme
kegg intermediate: Tetrahedral intermediate
pdb: 1bcrA
pdb: 1bcsA
pdb: 1whsA
pdb: 1whtA
pdb: 3sc2A
pdb: 1bcrB
pdb: 1bcsB
pdb: 1whsB
pdb: 1whtB
pdb: 3sc2B
pdb bound state: Unbound
  compound: Peptide
  pdb: 1bcrA
pdb bound state: Unbound
  compound: Peptide
  pdb: 1bcsA
pdb bound state: Unbound
  compound: Peptide
  pdb: 1whsA
pdb bound state: Unbound
  compound: Peptide
  pdb: 1whtA
pdb bound state: Unbound
  compound: Peptide
  pdb: 3sc2A
pdb bound state: Unbound
  compound: Peptide
  pdb: 1bcrB
pdb bound state: Unbound
  compound: Peptide
  pdb: 1bcsB
pdb bound state: Unbound
  compound: Peptide
  pdb: 1whsB
pdb bound state: Unbound
  compound: Peptide
  pdb: 1whtB
pdb bound state: Unbound
  compound: Peptide
  pdb: 3sc2B
pdb bound state: Unbound
  compound: Peptide
  pdb: 1bcrA
pdb bound state: Unbound
  compound: Peptide
  pdb: 1bcsA
pdb bound state: Unbound
  compound: Peptide
  pdb: 1whsA
pdb bound state: Unbound
  compound: Peptide
  pdb: 1whtA
pdb bound state: Unbound
  compound: Peptide
  pdb: 3sc2A
pdb bound state: Unbound
  compound: Peptide
  pdb: 1bcrB
pdb bound state: Unbound
  compound: Peptide
  pdb: 1bcsB
pdb bound state: Unbound
  compound: Peptide
  pdb: 1whsB
pdb bound state: Unbound
  compound: Peptide
  pdb: 1whtB
pdb bound state: Unbound
  compound: Peptide
  pdb: 3sc2B
pdb bound state: Unbound
  compound: L-Arginine
  pdb: 1whsA
pdb bound state: Unbound
  compound: L-Arginine
  pdb: 1whtA
pdb bound state: Unbound
  compound: L-Arginine
  pdb: 3sc2A
pdb bound state: Unbound
  compound: L-Arginine
  pdb: 1bcrB
pdb bound state: Unbound
  compound: L-Arginine
  pdb: 1bcsB
pdb bound state: Unbound
  compound: L-Arginine
  pdb: 1whsB
pdb bound state: Unbound
  compound: L-Arginine
  pdb: 1whtB
pdb bound state: Unbound
  compound: L-Arginine
  pdb: 3sc2B
pdb bound state: Unbound
  compound: L-Lysine
  pdb: 1bcrA
pdb bound state: Unbound
  compound: L-Lysine
  pdb: 1bcsA
pdb bound state: Unbound
  compound: L-Lysine
  pdb: 1whsA
pdb bound state: Unbound
  compound: L-Lysine
  pdb: 1whtA
pdb bound state: Unbound
  compound: L-Lysine
  pdb: 3sc2A
pdb bound state: Unbound
  compound: L-Lysine
  pdb: 1bcrB
pdb bound state: Unbound
  compound: L-Lysine
  pdb: 1bcsB
pdb bound state: Unbound
  compound: L-Lysine
  pdb: 1whsB
pdb bound state: Unbound
  compound: L-Lysine
  pdb: 1whtB
pdb bound state: Unbound
  compound: L-Lysine
  pdb: 3sc2B
pdb bound state: Unbound
  compound: Peptidyl-tetrahedral intermediate
  pdb: 1bcrA
references: Structure of wheat serine carboxypeptidase II at 3.5-A resolution. A new class of serine proteinase.
references: Refined atomic model of wheat serine carboxypeptidase II at 2.2-A resolution.
references: Structure of the complex of L-benzylsuccinate with wheat serine carboxypeptidase II at 2.0-A resolution.
references: Peptide aldehyde complexes with wheat serine carboxypeptidase II: implications for the catalytic mechanism and substrate specificity.
comment: This enzyme belongs to the peptidase family-S10. According to the literature [2], [3] & [4], this enzyme has got a catalytic triad, Ser146/His397/Asp338, and an oxyainon hole, made of the backbone amides of Tyr147 and Gly53. Thus, this enzyme also performs two-step reaction, acylation and deacylation, like other serine hydrolases. Ser146 acts as a nucleophile to attack on the carbonyl carbon atom to form an acyl-enzyme intermediate in the acylation process. Meanwhile, an Asp-His pair acts to deprotonate the hydroxyl of the catalytic serine to make it nucleophilic. In this pair of residues, a strong electrostatic interaction between the sidechains stabilizes the imidazolium cation developed during the catalysis, according to the paper [2]. Although the catalytic mechanism of this enzyme is very similar to those of other serine hydrolases, it has several distinct features (see [3] & [4]). Firstly, according to the paper [3], a C-terminal carboxylate of the substrate might atc as a proton sink for the catalytic His397. Here, in an acid-base preequilibrium, transfer of a proton from the protonated histidine to the substrate carboxylate neutralizes both the residue itself and the substrate, and then the conventional mechanism of serine hydrolases can proceed [3]. For this preequilibrium, the interaction of Glu145 with the substrate carboxylate might play an important role in the transition state [3]. Secondly, the stereochemistry of an enzymatic reaction seems to be opposite to that of other serine hydrolases, such as proteinase A (see [4]). This dissimilarity can distinguish these enzymes which have such a catalytic triad, Ser/His/Asp, in terms of evolution [4].

Rossmann fold
type: Cath
references: http://www.cathdb.info/version/latest/superfamily/3.40.50.1820
catalytic domain: index.html

Peptide
type: KeggSubstrate
references: KEGG:C00012
compound type: peptide/protein
type: KeggProduct

H2O
type: KeggSubstrate
references: KEGG:C00001
compound type: H2O
references: CHEBI:15377
references: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi

L-Arginine
type: KeggProduct
references: KEGG:C00062
compound type: amino acids
compound type: amine group
compound type: imine group
compound type: lipid
references: CHEBI:16467
references: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi

L-Lysine
type: KeggProduct
references: KEGG:C00047
compound type: amino acids
compound type: amine group
compound type: lipid
references: CHEBI:18019
references: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi

Peptidyl-tetrahedral intermediate
type: KeggIntermediate
references: KEGG:I00087

Acyl-enzyme
type: KeggIntermediate
references: KEGG:I00085

Tetrahedral intermediate
type: KeggIntermediate
references: KEGG:I00086

1bcrA
type: Pdb
references: 1bcr
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:1bcr
catalytic residue: SER 146
main chain in catalysis: GLY 53;TYR 147

1bcsA
type: Pdb
references: 1bcs
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:1bcs
catalytic residue: SER 146
main chain in catalysis: GLY 53;TYR 147

1whsA
type: Pdb
references: 1whs
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:1whs
catalytic residue: SER 146
main chain in catalysis: GLY 53;TYR 147

1whtA
type: Pdb
references: 1wht
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:1wht
catalytic residue: SER 146
main chain in catalysis: GLY 53;TYR 147

3sc2A
type: Pdb
references: 3sc2
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:3sc2
catalytic residue: SER 146
main chain in catalysis: GLY 53;TYR 147

1bcrB
type: Pdb
references: 1bcr
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:1bcr
catalytic residue: ASP 338;HIS 397

1bcsB
type: Pdb
references: 1bcs
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:1bcs
catalytic residue: ASP 338;HIS 397

1whsB
type: Pdb
references: 1whs
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:1whs
catalytic residue: ASP 338;HIS 397

1whtB
type: Pdb
references: 1wht
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:1wht
catalytic residue: ASP 338;HIS 397

3sc2B
type: Pdb
references: 3sc2
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:3sc2
catalytic residue: ASP 338;HIS 397

Structure of wheat serine carboxypeptidase II at 3.5-A resolution. A new class of serine proteinase.
type: BibliographicResource
comment: X-ray crystallography (3.5 Angstroms)
medline id: 90216664
references: http://www.ncbi.nlm.nih.gov/pubmed/2324088
journal: J Biol Chem
volume: 265
pages: 6528-31
published year: 1990
authors:
  item: Liao DI
  item: Remington SJ
references: P08819

Refined atomic model of wheat serine carboxypeptidase II at 2.2-A resolution.
type: BibliographicResource
comment: X-ray crystallography (2.2 Angstroms)
references: http://www.ncbi.nlm.nih.gov/pubmed/1390755
journal: Biochemistry
volume: 31
pages: 9796-812
published year: 1992
authors:
  item: Liao DI
  item: Breddam K
  item: Sweet RM
  item: Bullock T
  item: Remington SJ
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl

Structure of the complex of L-benzylsuccinate with wheat serine carboxypeptidase II at 2.0-A resolution.
type: BibliographicResource
comment: X-ray crystallography (2.0 Angstroms)
references: http://www.ncbi.nlm.nih.gov/pubmed/7727364
journal: Biochemistry
volume: 33
pages: 11127-34
published year: 1994
authors:
  item: Bullock TL
  item: Branchaud B
  item: Remington SJ
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl

Peptide aldehyde complexes with wheat serine carboxypeptidase II: implications for the catalytic mechanism and substrate specificity.
type: BibliographicResource
comment: X-ray crystallography (2.1/2.5 Angstroms)
references: http://www.ncbi.nlm.nih.gov/pubmed/8636973
journal: J Mol Biol
volume: 255
pages: 714-25
published year: 1996
authors:
  item: Bullock TL
  item: Breddam K
  item: Remington SJ
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl

IntermediateAnalogue
compound: Tetrahedral intermediate
pdb: 1bcrA
ligand het code: AIP

IntermediateAnalogue
compound: Tetrahedral intermediate
pdb: 1bcsA
ligand het code: CST

TransitionStateAnalogue
compound: Tetrahedral intermediate
pdb: 1whtA
ligand het code: BZS

ReferenceForCatalyticMechanism
reference index: 2
reference section: p.9801-9802

ReferenceForCatalyticMechanism
reference index: 3
reference section: p.11132-11134, Scheme 1

ReferenceForCatalyticMechanism
reference index: 4
reference section: p.719-720, p.722-723