DB code: S00374

RLCP classification 1.13.30000.10 : Hydrolysis
CATH domain 3.40.50.1820 : Rossmann fold Catalytic domain
E.C. 3.4.16.6
CSA 1bcr
M-CSA 1bcr
MACiE M0005

CATH domain Related DB codes (homologues)
3.40.50.1820 : Rossmann fold S00544 S00344 S00517 S00525 S00526 S00720 S00723 S00724 S00725 S00919 S00057 S00345 S00347 S00348 S00346 S00350 S00352 S00353 S00355 S00356 S00358 D00189 D00210 D00539 T00253

Uniprot Enzyme Name
UniprotKB Protein name Synonyms Contains MEROPS Pfam
P08819 Serine carboxypeptidase 2
EC 3.4.16.6
Serine carboxypeptidase II
Carboxypeptidase D
CPDW-II
CP-WII
Serine carboxypeptidase 2 chain A Serine carboxypeptidase II chain A
Serine carboxypeptidase 2 chain B Serine carboxypeptidase II chain B
S10.005 (Serine)
PF00450 (Peptidase_S10)
[Graphical View]

KEGG enzyme name
carboxypeptidase D
cereal serine carboxypeptidase II
Saccharomyces cerevisiae KEX1 gene product
carboxypeptidase Kex1
gene KEX1 serine carboxypeptidase
KEX1 carboxypeptidase
KEX1 proteinase
KEX1DELTAp
CPDW-II
serine carboxypeptidase
Phaseolus proteinase

UniprotKB: Accession Number Entry name Activity Subunit Subcellular location Cofactor
P08819 CBP2_WHEAT Preferential release of a C-terminal arginine or lysine residue. Carboxypeptidase II is a dimer, where each monomer is composed of two chains linked by a disulfide bond.

KEGG Pathways
Map code Pathways E.C.

Compound table
Substrates Products Intermediates
KEGG-id C00012 C00001 C00012 C00062 C00047 I00087 I00085 I00086
E.C.
Compound Peptide H2O Peptide L-Arginine L-Lysine Peptidyl-tetrahedral intermediate Acyl-enzyme Tetrahedral intermediate
Type peptide/protein H2O peptide/protein amino acids,amine group,imine group,lipid amino acids,amine group,lipid
ChEBI 15377
16467
18019
PubChem 22247451
962
28782
6322
5962
71774817
1bcrA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Bound:ARG_426 (chain D) Unbound Unbound Unbound Intermediate-analogue:AIP
1bcsA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Bound:ARG_426 (chain D) Unbound Unbound Unbound Intermediate-analogue:CST
1whsA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1whtA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Transition-state-analogue:BZS
3sc2A Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1bcrB Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1bcsB Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1whsB Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1whtB Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound
3sc2B Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound

Reference for Active-site residues
resource references E.C.

Active-site residues
PDB Catalytic residues Cofactor-binding residues Modified residues Main-chain involved in catalysis Comment
1bcrA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain SER 146 GLY 53;TYR 147
1bcsA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain SER 146 GLY 53;TYR 147
1whsA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain SER 146 GLY 53;TYR 147
1whtA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain SER 146 GLY 53;TYR 147
3sc2A Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain SER 146 GLY 53;TYR 147
1bcrB Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASP 338;HIS 397
1bcsB Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASP 338;HIS 397
1whsB Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASP 338;HIS 397
1whtB Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASP 338;HIS 397
3sc2B Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASP 338;HIS 397

References for Catalytic Mechanism
References Sections No. of steps in catalysis
[2]
p.9801-9802
[3]
p.11132-11134, Scheme 1
[4]
p.719-720, p.722-723

References
[1]
Resource
Comments X-ray crystallography (3.5 Angstroms)
Medline ID 90216664
PubMed ID 2324088
Journal J Biol Chem
Year 1990
Volume 265
Pages 6528-31
Authors Liao DI, Remington SJ
Title Structure of wheat serine carboxypeptidase II at 3.5-A resolution. A new class of serine proteinase.
Related PDB
Related UniProtKB P08819
[2]
Resource
Comments X-ray crystallography (2.2 Angstroms)
Medline ID
PubMed ID 1390755
Journal Biochemistry
Year 1992
Volume 31
Pages 9796-812
Authors Liao DI, Breddam K, Sweet RM, Bullock T, Remington SJ
Title Refined atomic model of wheat serine carboxypeptidase II at 2.2-A resolution.
Related PDB 3sc2
Related UniProtKB
[3]
Resource
Comments X-ray crystallography (2.0 Angstroms)
Medline ID
PubMed ID 7727364
Journal Biochemistry
Year 1994
Volume 33
Pages 11127-34
Authors Bullock TL, Branchaud B, Remington SJ
Title Structure of the complex of L-benzylsuccinate with wheat serine carboxypeptidase II at 2.0-A resolution.
Related PDB 1whs 1wht
Related UniProtKB
[4]
Resource
Comments X-ray crystallography (2.1/2.5 Angstroms)
Medline ID
PubMed ID 8636973
Journal J Mol Biol
Year 1996
Volume 255
Pages 714-25
Authors Bullock TL, Breddam K, Remington SJ
Title Peptide aldehyde complexes with wheat serine carboxypeptidase II: implications for the catalytic mechanism and substrate specificity.
Related PDB 1bcr 1bcs
Related UniProtKB

Comments
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].

Created Updated
2002-07-04 2011-02-16