DB code: S00407

RLCP classification 1.13.11110.262 : Hydrolysis
CATH domain 3.40.630.10 : Aminopeptidase Catalytic domain
E.C. 3.4.17.18
CSA
M-CSA
MACiE

CATH domain Related DB codes (homologues)
3.40.630.10 : Aminopeptidase D00512 S00406 D00192 D00193 D00467

Uniprot Enzyme Name
UniprotKB Protein name Synonyms MEROPS Pfam
P29068 Carboxypeptidase T
EC 3.4.17.18
M14.007 (Metallo)
PF00246 (Peptidase_M14)
[Graphical View]

KEGG enzyme name
carboxypeptidase T
CPT

UniprotKB: Accession Number Entry name Activity Subunit Subcellular location Cofactor
P29068 CBPT_THEVU Releases a C-terminal residue, which may be hydrophobic or positively charged. Monomer. Binds 1 zinc ion per subunit.

KEGG Pathways
Map code Pathways E.C.

Compound table
Cofactors Substrates Products Intermediates
KEGG-id C00038 C00017 C00012 C00001 C00017 C00012 C00045
E.C.
Compound Zinc Protein Peptide H2O Protein Peptide Amino acid
Type heavy metal peptide/protein peptide/protein H2O peptide/protein peptide/protein amino acids
ChEBI 29105
 29105
 		15377
 15377
PubChem 32051
 32051
 		22247451
 962
 22247451
 962
1obrA Bound:_ZN Unbound Unbound Bound:HOH_9 Unbound Unbound Unbound

Reference for Active-site residues
resource references E.C.
Swiss-prot;P29068 & literature [1],[2]

Active-site residues
PDB Catalytic residues Cofactor-binding residues Modified residues Main-chain involved in catalysis Comment
1obrA ARG 129;GLU 277 HIS 69;GLU 72;HIS 204(Zinc binding) THR 205

References for Catalytic Mechanism
References Sections No. of steps in catalysis
[1]
p.284-286

References
[1]
Resource
Comments X-ray crystallography (2.35 Angstroms)
Medline ID 92394121
PubMed ID 1521526
Journal Eur J Biochem
Year 1992
Volume 208
Pages 281-8
Authors Teplyakov A, Polyakov K, Obmolova G, Strokopytov B, Kuranova I, Osterman A, Grishin N, Smulevitch S, Zagnitko O, Galperina O, et al
Title Crystal structure of carboxypeptidase T from Thermoactinomyces vulgaris.
Related PDB 1obr
Related UniProtKB P29068
[2]
Resource
Comments
Medline ID
PubMed ID 1449602
Journal J Protein Chem
Year 1992
Volume 11
Pages 561-70
Authors Osterman AL, Grishin NV, Smulevitch SV, Matz MV, Zagnitko OP, Revina LP, Stepanov VM
Title Primary structure of carboxypeptidase T: delineation of functionally relevant features in Zn-carboxypeptidase family.
Related PDB
Related UniProtKB

Comments
This enzyme belongs to the peptidase family-M14.
This enzyme binds four calcium ions which seem to play an important role in the thermostability of the enzyme, according to the Swiss-prot data (P29068).
Moreover, this enzyme is homologous to carboxypeptidase A (E.C. 3.4.17.1; D00467 in EzCatDB), carboxypeptidase A2 (E.C. 3.4.17.15; D00193) and carboxypeptidase B (E.C. 3.4.17.2; D00512) with conserved catalytic residues. Thus, they might have the same catalytic mechanism.
According to the literature [1], the zinc-bound water molecule could be considered as a possible nucleophile, whilst Arg129 is believed to polarize the carbonyl of the scissile bond of the substrate as the stabilizer of the 'oxyanion hole'.
The paper [2] also characterized the catalytic residues as follows:
(1) Glu277 (of 1obr) promotes nucleophilic attack of H2O molecule on substrate carbonyl and subsequent proton transfer in general base mechanism.
(2) His69, Glu72 and His204 (of 1obr) are ligated to the zinc ion that is presumed to take part in H2O polarization and the stabilization of the tetrahedral intermediate.
(3) Arg129 (1obr) plays an essential role in stabilizing the tetrahedral intermediate.

Created Updated
2002-09-27 2009-02-26