Information on EC 3.4.17.22 - metallocarboxypeptidase D

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The enzyme appears in viruses and cellular organisms

EC NUMBER
COMMENTARY hide
3.4.17.22
-
RECOMMENDED NAME
GeneOntology No.
metallocarboxypeptidase D
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
releases C-terminal Arg and Lys from polypeptides
show the reaction diagram
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
hydrolysis of peptide bond
CAS REGISTRY NUMBER
COMMENTARY hide
153967-26-1
not distinguished from EC 3.4.16.6 in Chemical Abstracts
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
-
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
malfunction
physiological function
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
Dansyl-Ala-Arg + H2O
Dansyl-Ala + Arg
show the reaction diagram
Dansyl-Leu-Ala-Arg + H2O
Dansyl-Leu-Ala + Arg
show the reaction diagram
-
-
-
-
-
Dansyl-Leu-Arg + H2O
Dansyl-Leu + Arg
show the reaction diagram
-
-
-
-
-
Dansyl-Phe-Ala-Arg + H2O
Dansyl-Phe-Ala + Arg
show the reaction diagram
Dansyl-Phe-Gly-Arg + H2O
Dansyl-Phe-Gly + Arg
show the reaction diagram
Dansyl-Phe-Ile-Arg + H2O
Dansyl-Phe-Ile + Arg
show the reaction diagram
-
-
-
-
-
Dansyl-Phe-Leu-Arg + H2O
Dansyl-Phe-Leu + Arg
show the reaction diagram
-
-
-
-
-
Dansyl-Phe-Phe-Arg + H2O
Dansyl-Phe-Phe + Arg
show the reaction diagram
Dansyl-Phe-Pro-Arg + H2O
Dansyl-Phe-Pro + Arg
show the reaction diagram
-
-
-
-
-
Dansyl-Pro-Ala-Arg + H2O
Dansyl-Pro-Ala + Arg
show the reaction diagram
pGlu-Leu-Thr-Phe-Ser-Pro-Asp-Trp-Gly-Lys + H2O
pGlu-Leu-Thr-Phe-Ser-Pro-Asp-Trp-Gly + Lys
show the reaction diagram
-
adipokinetic hormone intermediates containing C-terminal basic residues is processed by CPD
-
-
?
pGlu-Leu-Thr-Phe-Ser-Pro-Asp-Trp-Gly-Lys-Arg + H2O
pGlu-Leu-Thr-Phe-Ser-Pro-Asp-Trp-Gly-Lys + Arg
show the reaction diagram
-
adipokinetic hormone intermediates containing C-terminal basic residues is processed by CPD
-
-
?
Tyr-Gly-Gly-Phe-Leu-Arg + H2O
Tyr-Gly-Gly-Phe-Leu + Arg
show the reaction diagram
-
-
-
-
?
Tyr-Gly-Gly-Phe-Leu-Lys + H2O
Tyr-Gly-Gly-Phe-Leu + Lys
show the reaction diagram
-
-
-
-
?
additional information
?
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
additional information
?
-
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Cd Cl2
-
activation of enzyme form gp170, inhibition of gp180
Co2+
-
activates
CoCl2
-
1 mM, activation
Zn2+
-
; two of the three luminal/extracellular domains bind Zn2+-ions
ZnCl2
-
1 mM, activation
additional information
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
1,10-phenanthroline
2-mercaptomethyl-3-guanidinoethylthiopropanoic acid
4-[[(3,4-dinitrophenyl)carbonyl]amino]-2-(6-hydroxy-3-oxo-3H-xanthen-9-yl)benzoic acid
-
-
Aprotinin
-
-
CdCl2
-
-
CuSO4
-
-
DL-2-mercaptomethyl-3-guanidinoethylthiopropanoic acid
;
dynorphin A
-
-
Guanidinoethylmercaptosuccinic acid
HgCl2
-
-
leupeptin
Met-enkephalin-KK
-
-
p-Chloromercuriphenylsulfonate
-
-
PCMB
-
-
siRNA
-
small interfering CPD RNA
-
siCPD RNA
-
Zn2+
-
ZnCl2
additional information
-
not inhibitory: iodoacetate, phenylmethylsulfonylfluoride, benzamidine, N-tosyl-L-Phe chloromethyl ketone, N- tosyl-L-Lys chloromethyl ketone
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
beta-estradiol
-
up-regulates CPD mRNA and protein expression
prolactin
-
up-regulates CPD mRNA and protein expression
-
transforming growth factor-beta
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.063 - 0.132
Dansyl-Ala-Arg
0.056 - 0.065
Dansyl-Leu-Ala-Arg
0.25
Dansyl-Leu-Arg
-
-
0.012 - 0.087
dansyl-Phe-Ala-Arg
0.047 - 0.15
dansyl-Phe-Gly-Arg
0.085
dansyl-Phe-Ile-Arg
-
-
0.042 - 0.048
dansyl-Phe-Leu-Arg
0.016 - 0.1
dansyl-Phe-Phe-Arg
0.11
dansyl-Phe-Pro-Arg
-
-
0.0092 - 0.054
Dansyl-Pro-Ala-Arg
0.115
Tyr-Gly-Gly-Phe-Leu-Arg
-
wild-type enzyme, pH 6.4, 37C
0.0305
Tyr-Gly-Gly-Phe-Leu-Lys
-
wild-type enzyme, pH 6.4, 37C
additional information
additional information
-
Km-values of domain 1 and 2
-
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
25
Dansyl-Leu-Ala-Arg
Bos taurus
-
-
0.0417
Dansyl-Leu-Arg
Bos taurus
-
-
19 - 57
dansyl-Phe-Ala-Arg
2.6 - 4.4
dansyl-Phe-Gly-Arg
0.07
dansyl-Phe-Ile-Arg
Bos taurus
-
-
4.5
dansyl-Phe-Leu-Arg
Bos taurus
-
-
3.7 - 17
dansyl-Phe-Phe-Arg
0.002
dansyl-Phe-Pro-Arg
Bos taurus
-
-
6.7 - 22
Dansyl-Pro-Ala-Arg
3.07
Tyr-Gly-Gly-Phe-Leu-Arg
Anas sp.
-
wild-type enzyme, pH 6.4, 37C
3.97
Tyr-Gly-Gly-Phe-Leu-Lys
Anas sp.
-
wild-type enzyme, pH 6.4, 37C
additional information
additional information
Anas sp.
-
turnover numbers of domain 1 and 2
-
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.0116 - 0.0451
1,10-phenanthroline
0.0093 - 0.0476
DL-2-mercaptomethyl-3-guanidinoethylthiopropanoic acid
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
5.5 - 6.5
-
-
5.5 - 6
-
-
5.5 - 6.5
-
soluble enzyme
6.4
-
placenta
7
domain I is most active at pH 7 whereas domain II is most active at pH 5.6
pH RANGE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
5.3 - 7.5
-
pH 5.3: about 45% of maximal activity, pH 7.5: about 35% of maximal activity
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
-
; ACTH-immunreactive cells outside clustered small cell island (CSCI) show a strong carboxypeptidase D immunoreactivity, whereas ACTH-immunreactive cells in clustered small cell island show uniformly weak reactivity
Manually annotated by BRENDA team
-
baseline expression
Manually annotated by BRENDA team
baseline expression
Manually annotated by BRENDA team
-
overexpressed in hepatocellular carcinoma
Manually annotated by BRENDA team
-
it is demonstrated that CpD is up-regulated by TGF-beta in murine macrophage cell lines ANA-1 and RAW 264.7 but HepG2 cells - cells not primarily associated with innate immune responses- show only minimal regulation of CpD by TGF-beta
Manually annotated by BRENDA team
; it is demonstrated that CpD is up-regulated by TGF-beta in CD14 + human blood monocytes
Manually annotated by BRENDA team
additional information
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
-
DCPD, glycine decarboxylase and duck Hepatitis B virus large enveloppe protein are colocalized in the endosomal fraction of duck hepatocytes
Manually annotated by BRENDA team
-
trans-Golgi network
Manually annotated by BRENDA team
also detectable in the cytosol after 24 h treatment with interleukin-2
Manually annotated by BRENDA team
additional information
-
CPD contains three luminal/extracellular carboxypeptidase E like domains of about 50 kDa each
-
Manually annotated by BRENDA team
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
135000
-
deglycosaylated enzyme
150000
-
antisera raised against the N-terminal region of the 1A form and the C-terminal region of the tail-2 form of CPD
153500
-
calculation from sequence of cDNA
160000
SDS-PAGE
170000
175000
-
x * 175000, SDS-PAGE
180000
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
proteolytic modification
-
enzyme is cleaved by furin. Proteins sequence reveals a consensus sequence for furin cleavage (RXXR) at positions 166 to 169. Cleavage at this site removes the N-terminal 169 residues to generate a truncated protein of approximately 151 kDa. Substitution of the two arginines with alanine completely abolishes cleavage of DCPD
Crystallization/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
crystal structure of carboxypeptidase D domain II, sitting drop vapour diffusion method
-
crystal structure of duck carboxypeptidase D domain II in a complex with the peptidomimetic inhibitor guanidinoethylmercaptosuccinic acid, occupying the specificity pocket; three-dimensional-structure of carboxypeptidase D domain II in a complex with the peptidomimetic inhibitor, guanidinoethylmercaptosuccinic acid,occupying the specificity pocket
-
Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
enzyme expressed in a Pichia pastoris system
-
enzyme form gp170, lacking the C-terminal transmembrane domain
-
large scale
-
on affinity resin
-
wild-type enzyme and various point mutants expressed in a baculovirus expression system
-
Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
baculovirus expression of constructs containing either the 1A or the 1B form and one of three different sequences of domain 2 of CPD (wild type, mutants svr1, or svrpoi) in Sf9 cells
-
expressed by transient expression in a human kidney cell line and primary duck hepatocytes
-
expression in Sf9 cells, using a baculovirus expression system
-
wild-type enzyme and point mutants are expressed at high levels in Sf9 cells using the baculovirus expression system
-
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
overexpressed in hepatocellular carcinoma
-
ENGINEERING
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
R166A/R169A
-
enzyme is cleaved by furin. Proteins sequence reveals a consensus sequence for furin cleavage (RXXR) at positions 166 to 169. Cleavage at this site removes the N-terminal 169 residues to generate a truncated protein of approximately 151 kDa. Substitution of the two arginines with alanine completely abolishes cleavage of DCPD
additional information
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
medicine
additional information
-
Drosophila CPD is encoded by the silver gene svr, which is differentially spliced to produce long transmembrane protein forms with three metallocarboxypeptidase-like domains and short soluble forms with a single metallocarboxypeptidase domain. Flies that retain the short form are viable, whereas flies that are missing all forms of CPD do not survive past the early larval stages