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 15377		16467 16467	18019 18019
PubChem		22247451 962 22247451 962		28782 6322 28782 6322	5962 71774817 5962 71774817

1bcrA	Unbound		Unbound	Bound:ARG_426 (chain D)	Unbound	Unbound	Unbound	Intermediate-analogue:AIP
1bcsA	Unbound		Unbound	Bound:ARG_426 (chain D)	Unbound	Unbound	Unbound	Intermediate-analogue:CST
1whsA	Unbound		Unbound	Unbound	Unbound	Unbound	Unbound	Unbound
1whtA	Unbound		Unbound	Unbound	Unbound	Unbound	Unbound	Transition-state-analogue:BZS
3sc2A	Unbound		Unbound	Unbound	Unbound	Unbound	Unbound	Unbound
1bcrB	Unbound		Unbound	Unbound	Unbound	Unbound	Unbound	Unbound
1bcsB	Unbound		Unbound	Unbound	Unbound	Unbound	Unbound	Unbound
1whsB	Unbound		Unbound	Unbound	Unbound	Unbound	Unbound	Unbound
1whtB	Unbound		Unbound	Unbound	Unbound	Unbound	Unbound	Unbound
3sc2B	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	SER 146			GLY 53;TYR 147
1bcsA	SER 146			GLY 53;TYR 147
1whsA	SER 146			GLY 53;TYR 147
1whtA	SER 146			GLY 53;TYR 147
3sc2A	SER 146			GLY 53;TYR 147
1bcrB	ASP 338;HIS 397
1bcsB	ASP 338;HIS 397
1whsB	ASP 338;HIS 397
1whtB	ASP 338;HIS 397
3sc2B	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].

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