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Enzyme Nomenclature
Information on EC 3.4.17.1 - carboxypeptidase A
for references in articles please use BRENDA:EC3.4.17.1
Word Map on EC 3.4.17.1
- 3.4.17.1
-
cyclopiazonic
- cyclophosphamide
-
cerebellopontine
- artery
- nerve
-
cyproterone
-
n6-cyclopentyladenosine
-
cryoprotective
-
contract
-
sarcoplasmic
-
cryopreservation
-
hearing
-
postoperative
-
facial
-
auditory
-
chemokines
-
cranial
-
aversion
-
ca2+-atpase
- dpcpx
- schwannomas
-
vestibular
- meningioma
-
acoustic
-
cardiopulmonary
- caffeine
- thapsigargin
-
ryanodine
-
ca2+-free
-
antiandrogens
-
rantes
- nifedipine
-
fossa
-
resuscitation
- aspergillosis
- tryptase
-
store-operated
- neuralgia
- chymase
-
craniotomy
- sercas
- lipoma
-
mip-1beta
-
mip-1alpha
- tinnitus
- 2-chloroadenosine
- hirsutism
-
hemifacial
- vertigo
- synthesis
- pharmacology
- food industry
- drug development
- analysis
-
out-of-hospital
- medicine
- biotechnology
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The enzyme appears in viruses and cellular organisms
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EC NUMBER 
COMMENTARY 
3.4.17.1
-
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RECOMMENDED NAME
GeneOntology No.
carboxypeptidase A
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REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
release of a C-terminal amino acid, but little or no action with -Asp, -Glu, -Arg, -Lys or -Pro
release of a C-terminal amino acid, but little or no action with -Asp, -Glu, -Arg, -Lys or -Pro
correlations between mechanism, kinetics, and structure, intermediates and rate-determining steps; mechanism
-
release of a C-terminal amino acid, but little or no action with -Asp, -Glu, -Arg, -Lys or -Pro
rapid release: Tyr, Phe, Trp, Leu, Ile, Thr, Gln, His, Ala, Val, homoserine, slow release: Asn, Ser, Lys, MetSO2, very slow release: Gly, Asp, Glu, CySO3H, S-carboxymethylcysteine, not released: Pro, Hyp, Arg
-
release of a C-terminal amino acid, but little or no action with -Asp, -Glu, -Arg, -Lys or -Pro
mechanism; promoted water pathway, mechanistic model
-
release of a C-terminal amino acid, but little or no action with -Asp, -Glu, -Arg, -Lys or -Pro
mechanism
-
release of a C-terminal amino acid, but little or no action with -Asp, -Glu, -Arg, -Lys or -Pro
mechanism; relationships between structure and mechanism, different catalytic sites for esters and peptides, role of mechanic strain discussed
-
release of a C-terminal amino acid, but little or no action with -Asp, -Glu, -Arg, -Lys or -Pro
mechanism; relationships between structure and mechanism, zinc environment and substrate complexes
-
release of a C-terminal amino acid, but little or no action with -Asp, -Glu, -Arg, -Lys or -Pro
cryospectrokinetic characterization of intermediates, time-course of reaction; mechanism
-
release of a C-terminal amino acid, but little or no action with -Asp, -Glu, -Arg, -Lys or -Pro
mechanism; pK values of active site residues, analysis of kinetics and mechanism under alkaline conditions
-
release of a C-terminal amino acid, but little or no action with -Asp, -Glu, -Arg, -Lys or -Pro
evidence for acyl-enzyme intermediates; mechanism
-
release of a C-terminal amino acid, but little or no action with -Asp, -Glu, -Arg, -Lys or -Pro
evidence of general base pathway; mechanism
-
release of a C-terminal amino acid, but little or no action with -Asp, -Glu, -Arg, -Lys or -Pro
conceptual model of relationship between activity, mechanism and conformational mobility; mechanism
-
release of a C-terminal amino acid, but little or no action with -Asp, -Glu, -Arg, -Lys or -Pro
molecular dynamics characterization of active cavity
-
release of a C-terminal amino acid, but little or no action with -Asp, -Glu, -Arg, -Lys or -Pro
mechanism; mechanisms elucidated from complex with inactivator 2-benzyl-3-iodo-propanoic acid
-
release of a C-terminal amino acid, but little or no action with -Asp, -Glu, -Arg, -Lys or -Pro
relationships between enzyme structure and catalytic properties, catalytic groups, intermediates, and conformational changes during catalysis conform to 'induced fit hypothesis'
-
-
-
release of a C-terminal amino acid, but little or no action with -Asp, -Glu, -Arg, -Lys or -Pro
residues Glu270 and Arg127 are important for activity, the catalytic triad consists of Ile275, Tyr248, and Ala250, residues at positions 202, 254, and 268 are important for substrate specificity
release of a C-terminal amino acid, but little or no action with -Asp, -Glu, -Arg, -Lys or -Pro
catalytic mechanism involving the Zn2+ ion and residue Glu270 with ester or protein substrates, the tetrahydrate transition state is stabilized by Arg127, overview
-
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
hydrolysis
hydrolysis of peptide bond
hydrolysis of peptide bond
-
hydrolysis of peptide bond
-
hydrolysis of peptide bond
-
-
hydrolysis of peptide bond
-
-
exopeptidase, cleaves from C-terminus
-
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CAS REGISTRY NUMBER
COMMENTARY
11075-17-5
-
9031-98-5
-
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ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
-
36319, 36320, 36322, 36327, 36328, 36331, 36339, 36340, 36341, 36342, 36343, 36344, 36345, 36346, 36347, 36348, 36349, 36350, 36352, 36353, 36354, 36355, 36356, 36357, 36358, 36359, 36361, 36362, 36363, 36364, 36365, 649223, 649937, 649996, 650016, 650523, 650531, 650532, 650534, 650547, 650549, 650550, 651059, 652743, 652994, 667614, 668127, 668360, 669867, 669909, 683066, 683187, 683198, 683367, 683428, 683487, 683577, 683592, 683762, 684046, 699085, 704198
-
-
also two allotypic forms known; overview, forms alpha, beta, gamma, and delta may result from slightly different activation conditions
-
-
heterogeneity: 5 molecular species that differ in amino acid composition and heat stability, but not in catalytic properties
-
-
overview, forms alpha, beta, gamma, and delta may result from slightly different activation conditions
-
-
-
36320, 36321, 36329, 650534, 667298, 668995, 670465, 670684, 671003, 678979, 683036, 683370, 683382, 683818, 684017, 686638, 687160, 689901, 703161, 704153, 704669, 705857, 706657, 706874
-
-
carboxypeptidase A 2, evolutionary relationships between rat carboxypeptidases
-
-
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GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
physiological function
physiological function
-
molting fluid carboxypeptidase A is involved in degradation of the proteins from the old cuticle and recycling of the amino acids, the enzyme plays important role in hydrolyzing the vitellogenic proteins which are the source of nutrition for maintaining embryonic development
physiological function
-
CPA participates in the apolysis of the integument during larval molting and metamorphosis
physiological function
-
CPA4 functions in neuropeptide processing and regulation in the extracellular environment
physiological function
-
MC-CPA plays a role in regulating innate immunity responses, including the degradation of harmful substances such as the vasoconstrictive factor endothelin 1 and snake venomtoxins
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SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
3-(2-furyl)acryloyl-L-Phe-L-Ala + H2O
3-(2-furyl)acryloyl-L-Phe + L-Ala
-
-
-
-
?
3-(2-furyl)acryloyl-L-Phe-L-Ile + H2O
3-(2-furyl)acryloyl-L-Phe + L-Ile
-
-
-
-
?
3-(2-furyl)acryloyl-L-Phe-L-Leu + H2O
3-(2-furyl)acryloyl-L-Phe + L-Leu
-
-
-
-
?
3-(2-furyl)acryloyl-L-Phe-L-Met + H2O
3-(2-furyl)acryloyl-L-Phe + L-Met
-
-
-
-
?
3-(2-furyl)acryloyl-L-Phe-L-Phe + H2O
3-(2-furyl)acryloyl-L-Phe + L-Phe
-
-
-
-
?
3-(2-furyl)acryloyl-L-Phe-L-Trp + H2O
3-(2-furyl)acryloyl-L-Phe + L-Trp
-
-
-
-
?
3-(2-furyl)acryloyl-L-Phe-L-Val + H2O
3-(2-furyl)acryloyl-L-Phe + L-Val
-
-
-
-
?
4-chlorocinnamoyl-L-beta-phenyllactate + H2O
4-chlorocinnamic acid + L-beta-phenyllactate
-
-
-
-
?
5-dimethyl-aminonaphthalene-1-sulfonyl-Ala-Ala-L-beta-phenyllactate + H2O
5-dimethyl-aminonaphthalene-1-sulfonyl-Ala-Ala + L-beta-phenyllactate
-
-
-
ir
5-dimethyl-aminonaphthalene-1-sulfonyl-Ala-Ala-Phe + H2O
5-dimethyl-aminonaphthalene-1-sulfonyl-Ala-Ala + L-Phe
-
-
-
ir
benzoyl-Gly-Gly-L-alpha-hydroxy-beta-phenyllactate + H2O
benzoyl-Gly-Gly-L-alpha-hydroxy-beta-phenyllactate + ?
-
-
-
ir
carbobenzyloxy-Gly-hippuryl-L-Phe + H2O
carbobenzyloxy-Gly-hippuric acid + L-Phe
-
-
-
ir
carboxypeptidase A5 C-terminus + H2O
?
-
requires an overnight incubation for a partial digestion by CPA4
-
-
?
glycyl-L-serylglycyl-L-seryl-N-(2,3-diazabicyclo[2.2.2]oct-2-en-1-ylmethyl)-L-asparaginylglycyl-L-seryl-L-tryptophan + H2O
glycyl-L-serylglycyl-L-seryl-N-(2,3-diazabicyclo[2.2.2]oct-2-en-1-ylmethyl)-L-asparaginylglycyl-L-serine + L-tryptophan
-
2,3-diazabicyclo[2.2.2]oct-2-ene-labeled asparagine as a fluorescent amino acid
-
-
?
hippuryl-DL-beta-phenyllactic acid + H2O
hippuric acid + 3-phenyllactic acid
-
-
-
ir
hippuryl-DL-phenylacetic acid + H2O
hippuric acid + DL-phenyllactic acid
-
-
-
ir
hippuryl-DL-phenylalanine + H2O
hippuric acid + DL-phenylalanine
-
-
-
-
?
hippuryl-DL-phenyllactic acid + H2O
hippuric acid + DL-phenyllactic acid
-
-
-
-
?
hippuryl-L-Phe + H2O
hippuric acid + L-phenylalanine
-
the hydrolysis of the hippuryl-L-Phe molecule by carboxypeptidase A is investigated using both density functional theory and a hybrid quantum mechanical/molecular mechanical approach. The enzymatic reaction is found to proceed via a promoted water pathway with Glu270 serving as the general base and general acid. Free-energy calculations indicate that the first nucleophilic addition step is rate-limiting, with a barrier of 17.9 kcal/mol. Besides activating the zinc-bound water nucleophile, the zinc cofactor also serves as an electrophilic catalyst that stabilizes the substrate carbonyl oxygen during the formation of the tetrahedral intermediate. In the Michaelis complex, Arg127, rather than Zn(II), is responsible for the polarization of the substrate carbonyl and it also serves as the oxyanion hole
-
-
?
L-beta-phenyllactate-alpha-((2-naphthoyl)amino)-cinnamoyl ester + H2O
L-beta-phenyllactate + alpha-((2-naphthoyl)amino) cinnamate
-
-
-
ir
L-beta-phenyllactate-alpha-(acetylamino)-cinnamoyl ester + H2O
L-beta-phenyllactate + alpha-(acetylamino)cinnamate
-
-
-
ir
L-beta-phenyllactate-alpha-(benzoylylamino)-cinnamoyl ester + H2O
L-beta-phenyllactate + alpha-(benzoylamino)-cinnamate
-
-
-
ir
Met-enkephalin + H2O
?
-
requires an overnight incubation for a partial digestion by CPA4
-
-
?
methotrexate-alpha-(1-naphthyl)alanine + H2O
methotrexate + (1-naphthyl)alanine
-
low activity
-
-
?
methotrexate-alpha-phenylalanine + H2O
methotrexate + phenylalanine
-
high activity
-
-
?
N-(2,3-diazabicyclo[2.2.2]oct-2-en-1-ylmethyl)-L-asparaginylglycyl-L-tryptophan + H2O
N-(2,3-diazabicyclo[2.2.2]oct-2-en-1-ylmethyl)-L-asparaginylglycine + L-tryptophan
-
2,3-diazabicyclo[2.2.2]oct-2-ene-labeled asparagine as a fluorescent amino acid
-
-
?
N-(2,3-diazabicyclo[2.2.2]oct-2-en-1-ylmethyl)-L-asparaginylglycylglycyl-L-tryptophan + H2O
N-(2,3-diazabicyclo[2.2.2]oct-2-en-1-ylmethyl)-L-asparaginylglycylglycine + L-tryptophan
-
2,3-diazabicyclo[2.2.2]oct-2-ene-labeled asparagine as a fluorescent amino acid
-
-
?
N-(3-[2-furyl]acryloyl)-L-Phe-L-Phe + H2O
N-(3-[2-furyl]acryloyl)-L-Phe + L-Phe
-
-
-
-
?
N-(3-[2-furyl]acryloyl)-Phe-Phe + H2O
?
substrate of carboxypeptidase activity assay
-
-
?
N-(3-[2-furyl]acryloyl)-Phe-Phe + H2O
N-(3-[2-furyl]acryloyl)-Phe + Phe
-
-
-
-
?
N-(4-methoxyphenylazoformyl)-Phe-OH + H2O
?
-
substrate for inhibition assay
-
-
?
N-(trans-3-indoleacryloyl)-L-Phe + H2O
trans-3-indoleacrylate + L-Phe
-
-
-
ir
N-acetyl-Gly-L-phenyllactic acid + H2O
N-acetyl-Gly + L-phenyllactic acid
-
-
-
ir
N-carbobenzoxy-Gly-Gly-L-Leu + H2O
N-carbobenzoxy-Gly-Gly + L-Leu
-
-
-
ir
N-carbobenzoxy-Gly-Gly-L-Phe + H2O
N-carbobenzoxy-Gly-Gly + L-Phe
-
-
-
ir
N-[3-(2-furyl)acryloyl]-Phe-Phe + H2O
N-[3-(2-furyl)acryloyl]-Phe + Phe
-
-
-
?
N-[3-(2-furyl)]acryloyl-L-Phe-L-Phe + H2O
N-[3-(2-furyl)]acryloyl-L-Phe + L-Phe
-
-
-
?
N2acetyl-N-(2,3-diazabicyclo[2.2.2]oct-2-en-1-ylmethyl)-L-asparaginyl-L-tryptophan + H2O
N2-acetyl-N-(2,3-diazabicyclo[2.2.2]oct-2-en-1-ylmethyl)-L-asparagine + L-tryptophan
-
2,3-diazabicyclo[2.2.2]oct-2-ene-labeled asparagine as a fluorescent amino acid
-
-
?
O-(trans-4-chlorocinnamoyl)-L-beta-phenyllactate + H2O
trans-4-chlorocinnamic acid + L-phenyllactic acid
-
-
-
-
?
O-(trans-4-chlorocinnamoyl)-L-phenyllactic acid + H2O
trans-4-chlorocinnamic acid + L-phenyllactic acid
-
-
-
-
?
peptidyl-L-amino acid + H2O
?
-
rapid release: Tyr, Phe, Trp, Leu, Ile, Thr, Gln, His, Ala, Val, homoserine, slow release: Asn, Ser, Lys, MetSO2, very slow release: Gly, Asp, Glu, CysSO3, S-carboxymethylcysteine, not released: Pro, hydroxyproline, Arg, enzyme generally releases C-terminal amino acids, with the exception of C-terminal arginine, lysine and proline
-
-
-
Phe-Asn-Arg-Pro-Val + H2O
?
used as substrate in the activity assay
-
-
?
Phe-Asn-Arg-Pro-Val-Asp + H2O
?
used as substrate in the activity assay
-
-
?
Phe-Asn-Arg-Pro-Val-Val + H2O
?
used as substrate in the activity assay
-
-
?
voltage-dependent anion channel protein 1 C-terminus + H2O
?
-
weak substrate
-
-
?
Angiotensin I + H2O
?
-
partial cleavage of about 50% of angiotensin is found after 30 min of incubation with CPA4
-
-
?
angiotensin I + H2O
angiotensin II + His-Leu
-
shown in an ex vivo system of peritoneal exudates cells
-
-
?
angiotensin I + H2O
angiotensin II + His-Leu
-
shown in an ex vivo system of peritoneal exudates cells
-
-
?
angiotensin I + H2O
angiotensin II + His-Leu
-
shown in an ex vivo system of peritoneal exudates cells
-
-
?
hippuryl-DL-phenyllactate + H2O
hippuric acid + DL-phenyllactate
Cephalopina titillator
-
-
-
-
?
hippuryl-DL-phenyllactate + H2O
hippuric acid + DL-phenyllactate
-
-
-
ir
hippuryl-DL-phenyllactate + H2O
hippuric acid + DL-phenyllactate
-
-
-
ir
hippuryl-DL-phenyllactate + H2O
hippuric acid + DL-phenyllactate
-
-
-
ir
hippuryl-L-phenylalanine + H2O
hippuric acid + L-phenylalanine
-
assay substrate
-
-
?
hippuryl-L-phenylalanine + H2O
hippuric acid + L-phenylalanine
-
-
-
-
?
methotrexate-phenylalanine + H2O
methotrexate + phenylalanine
-
prodrug activation in SW122 cells
-
-
?
ochratoxin A + H2O
ochratoxin alpha + L-beta-phenylalanine
-
-
-
-
?
additional information
?
-
-
human haemoglobin, removal of specific C-terminal residues
-
-
-
additional information
?
-
-
chicken gizzard tropomyosin, effects on interaction between tropomyosin and actomyosin ATPase
-
-
-
additional information
?
-
-
CPA catalyzes the elimination of the C-terminal amino acid via hydrolysis, with a preference toward residues with hydrophobic side chains
-
-
-
additional information
?
-
the enzyme is a secretory granule metalloexopeptidase, MC-CPA is unique among carboxypeptidases inthaving a CPA-like substrate-binding pocket and enzymatic activity despite overall protein and gene structures more similar to CPB
-
-
-
additional information
?
-
-
CPVL colocalizes with both macrophage-inhibitory protein-1alpha and tumour necrosis factor-alpha
-
-
-
additional information
?
-
-
CPA4 is able to cleave hydrophobic C-terminal residues with a preference for Phe, Leu, Ile, Met, Tyr, and Val. Aliphatic, aromatic, and basic residues in the P1 position have a positive influence on the cleavage specificity. In contrast, acidic residues, Pro, and Gly have a negative influence in the P1 position
-
-
-
additional information
?
-
-
neither bradykinin nor des-Arg9-bradykinin or 3-(2-furyl)acryloyl-L-Phe-L-His are substrates for CPA4
-
-
-
additional information
?
-
-
the enzyme cleaves C-terminal hydrophobic aliphatic and aromatic residues from other peptides and proteins, not of food in contrast to pancreatic CPA1 and CPA2, for destruction, presumably following the action of chymase
-
-
-
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NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
methotrexate-phenylalanine + H2O
methotrexate + phenylalanine
-
prodrug activation in SW122 cells
-
-
?
peptidyl-L-amino acid + H2O
?
-
rapid release: Tyr, Phe, Trp, Leu, Ile, Thr, Gln, His, Ala, Val, homoserine, slow release: Asn, Ser, Lys, MetSO2, very slow release: Gly, Asp, Glu, CysSO3, S-carboxymethylcysteine, not released: Pro, hydroxyproline, Arg, enzyme generally releases C-terminal amino acids, with the exception of C-terminal arginine, lysine and proline
-
-
-
additional information
?
-
-
CPA catalyzes the elimination of the C-terminal amino acid via hydrolysis, with a preference toward residues with hydrophobic side chains
-
-
-
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METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Cd2+
Co2+
Mn2+
Ni2+
Zn2+
additional information
Cd2+
-
efficiency of metals in decreasing order: Zn, Co, Ni, Mn, Cd; substitution for native Zn, activates apoenzyme
Co2+
-
X-ray absorption fine study of Co environment in active site, comparison to Zn metalloenzyme
Co2+
-
efficiency of metals in decreasing order: Zn, Co, Ni, Mn, Cd; substitution for native Zn
Mn2+
-
efficiency of metals in decreasing order: Zn, Co, Ni, Mn, Cd; substitution for native Zn
Ni2+
-
efficiency of metals in decreasing order: Zn, Co, Ni, Mn, Cd; substitution for native Zn
Zn2+
-
1 mol Zn per mol of enzyme; His-69, Glu-72 and His-196 bind Zn to carboxypeptidase; metalloenzyme; required; Zn ligand is His, Zn involved in both binding and catalysis
Zn2+
-
1 mol Zn bound to a single polypeptide, acts as electrophilic catalyst; metalloenzyme
Zn2+
-
Zn enhances kinetic inhibition by imidazole 560fold due to formation of ternary complexes with enzyme
Zn2+
-
X-ray absorption fine study of Zn environment in active site, comparison to Co metalloenzyme
Zn2+
-
metalloenzyme, the amount of zinc excreted by the pancreas is related to enzyme output, quantitative determination, overview
Zn2+
zinc-metallopeptidase, binding residues are H69, E72, and H196
Zn2+
a zinc binding site is indentified by sequence analysis of cDNA clones; a zinc binding site is indentified by sequence analysis of cDNA clones; a zinc binding site is indentified by sequence analysis of cDNA clones; a zinc binding site is indentified by sequence analysis of cDNA clones; a zinc binding site is indentified by sequence analysis of cDNA clones; a zinc binding site is indentified by sequence analysis of cDNA clones; a zinc binding site is indentified by sequence analysis of cDNA clones
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INHIBITORS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
(2S)-2-([hydroxy[(1R)-1-[[1-(1,4,7,10-tetraazacyclododecan-1-ylacetyl)-L-prolyl]amino]ethyl]phosphoryl]oxy)-3-phenylpropanoic acid
-
i.e. IPro2
(2S)-2-([hydroxy[(1R)-1-[[N-(1,4,7,10-tetraazacyclododecan-1-ylacetyl)-b-alanyl]amino]ethyl]phosphoryl]oxy)-3-phenylpropanoic acid
-
i.e. I-beta-Ala2
(2S)-2-([hydroxy[(1R)-1-[[N-(1,4,7,10-tetraazacyclododecan-1-ylacetyl)-L-alanyl]amino]ethyl]phosphoryl]oxy)-3-phenylpropanoic acid
-
i.e. IAla2
(2S)-2-([hydroxy[(1R)-1-[[N-(1,4,7,10-tetraazacyclododecan-1-ylacetyl)-L-phenylalanyl]amino]ethyl]phosphoryl]oxy)-3-phenylpropanoic acid
-
i.e. IPhe2
(2S)-2-([hydroxy[(1R)-1-[[N-(1,4,7,10-tetraazacyclododecan-1-ylacetyl)glycyl]amino]ethyl]phosphoryl]oxy)-3-phenylpropanoic acid
-
i.e. IGly2
(2S)-2-([hydroxy[(1S)-1-[[1-(1,4,7,10-tetraazacyclododecan-1-ylacetyl)-L-prolyl]amino]ethyl]phosphoryl]oxy)-3-phenylpropanoic acid
-
i.e. IPro1
(2S)-2-([hydroxy[(1S)-1-[[N-(1,4,7,10-tetraazacyclododecan-1-ylacetyl)-b-alanyl]amino]ethyl]phosphoryl]oxy)-3-phenylpropanoic acid
-
i.e. I-beta-Ala1
(2S)-2-([hydroxy[(1S)-1-[[N-(1,4,7,10-tetraazacyclododecan-1-ylacetyl)-L-alanyl]amino]ethyl]phosphoryl]oxy)-3-phenylpropanoic acid
-
i.e. IAla1
(2S)-2-([hydroxy[(1S)-1-[[N-(1,4,7,10-tetraazacyclododecan-1-ylacetyl)-L-phenylalanyl]amino]ethyl]phosphoryl]oxy)-3-phenylpropanoic acid
-
i.e. IPhe1
(2S)-2-([hydroxy[(1S)-1-[[N-(1,4,7,10-tetraazacyclododecan-1-ylacetyl)glycyl]amino]ethyl]phosphoryl]oxy)-3-phenylpropanoic acid
-
i.e. IGly1
(2S)-2-[(hydroxy[(1R)-1-[(1,4,7,10-tetraazacyclododecan-1-ylacetyl)amino]ethyl]phosphoryl)oxy]-3-phenylpropanoic acid
-
i.e. I2
(R)-2-benzyl-3-nitropropanoic acid
-
; X-ray crystallography discloses that the nitro group well mimics the transition state occurred in the hydrolysis catalyzed by CPA, that is, an O,O'-bidentate coordination to the zinc ion and the two respective hydrogen bonds with Glu-270 and Arg-127. Because the nitro group is a planar species, (R)-2-benzyl-3-nitropropanoic acid is as a pseudo-transition-state analog inhibitor against CPA
(S)-2-(Hydroxy-[(S)-1-[(S)-3-methyl-2-(2-1,4,7,10tetraaza-cyclododec-1-yl-acetylamino)-pentanoylamino]-ethyl]-phosphinoyloxy)-3-phenyl-propionic acid
-
i.e. IIle1; i.e. IIle2
2-benzyl-3-iodo-propanoic acid
-
mechanisms elucidated from complex with inactivator
alpha-benzyl-2-oxo-1,3-oxazolidine-4-acetic acid
-
all four stereoisomers inhibit in a time dependent manner, inhibited enzyme does not regain its enzymatic activity upon dialysis, inactivation is prevented by 2-benzylsuccinic acid
-
imidazole
-
Zn2+ enhances kinetic inhibition by imidazole 560fold due to formation of ternary complexes with enzyme
N-(1,4,7,10-tetraazacyclododecan-1-ylacetyl)glycyl-N-[(1R)-1-[[(1S)-1-carboxy-2-phenylethoxy](hydroxy)phosphoryl]ethyl]glycinamide
-
i.e. IGlyGly2
N-(1,4,7,10-tetraazacyclododecan-1-ylacetyl)glycyl-N-[(1S)-1-[[(1S)-1-carboxy-2-phenylethoxy](hydroxy)phosphoryl]ethyl]glycinamide
-
i.e. IGlyGly1
N-(2-chloroethyl)-N-methylphenylalanine
-
both enantiomers, computational analysis of the mechanism for reactive inhibition, quantum mechanical and molecular mechanical methods, the inhibitor enantiomers both bind at the active site and perform nucleophilic deactivation involving cofactor Zn2+, overview
O-(hydroxyacetyl)-beta-phenyllactate
-
irreversible inactivation, Kinact/Ki: 57 M-1s-1
O-[[(1R)-(N-phenylmethoxycarbonyl)-L-alanyl]aminoethyl]hydroxyphosphinyl-L-3-phenyllactate
-
-
Proteins from Ascaris lumbricoides
-
molecular weight 7600, Ki in nM range, extensive structural analysis of inhibitors
-
Carbobenzoxyglycine
-
activator of dipeptide hydrolysis, inhibitor of tripeptide hydrolysis, Ki: 27 mM
Cd2+
-
decreases carboxypeptidase A activity probably due to the direct inhibition by the metal
D-Cys
-
binds tightly to the active site zinc. D-Cys binds the active site zinc with a sulfur ligand and forms additional interactions with surrounding side chains of the enzyme. D-Cys binding induces a concerted motion of the side chains around the sinc ion
D-penicillamine
-
catalyzes Zn2+ transfer from carboxypeptidase A to chelators, catalytic chelation
EDTA
-
complete inhibition of CPA4 activity s only achieved using a 100 mM concentration of EDTA in an overnight incubation, whereas the same inhibitor concentration causes only 60% inhibition after 5 h of treatment
latexin
-
from mouse recombinantly expressed as His-tagged enzyme in Escherichia coli and purified, overview, analysis of complex formation with CPAI, overview
-
latexin
-
cloned from human brain and expressed in Escherichia coli, CPA4-latexin complex structure determination and analysis
-
latexin
-
a carboxypeptidase A inhibitor protein, inhibits mast-cell CPA, CPA1, and CPA2, is associated with granular structures distinct from secretory granules and lysosomes in peritoneal mast cells, purification from and expression analysis in peritoneal mast cell granules, overview; a carboxypeptidase A inhibitor protein, inhibits mast-cell CPA, CPA1, and CPA2, is associated with intracellular granular structures distinct from MCCPA- and histamine-containing secretory granules and lysosomes in peritoneal mast cells, purification from and expression analysis in peritoneal mast cell granules, overview
-
leech carboxypeptidase inhibitor
-
LCI, tight-binding, competitive inhibition, the inhibitor contains four disulfide bonds, biding structure with CPA, oxidative folding pathway and intermediate of wild-type and mutant C19A/C43A mutant, determination of thermodynamics and conformational stability of wild-type and mutant enzymes at pH 8.4/high concentration of DTT, overview
-
potato carboxypeptidase inhibitor
-
molecular weight 38000, detailed study of inhibitor effects, stability, physical properties, purification protocol
-
potato carboxypeptidase inhibitor
-
i.e. PCI, wild-type and several mutants, oxidative folding, hydrogen exchange, and conformational stability, overview, secondary contact binding site structure and mechanism dependent, recombinant expression of the inhibitor protein in Escherichia coli, overview, steady-state binding kinetics
-
tick carboxypeptidase inhibitor
-
i.e. TCI, a 75 amino acid, two-domain protein from the blood-sucking tick Rhipcephalus bursa, recombinantly expressed in Escherichia coli and purified, three-dimensional structure of the enzyme-inhibitor protein complex, inhibitor binding and inhibition mechanism, overview
-
additional information
-
substrate inhibition by: carbobenzoxy-Glyl-L-Phe, benzoyl-Gly-Phe
-
additional information
-
study about coordination of low molecular weight inhibitors to metal ion
-
additional information
-
analysis of interactions between enzyme and multiple inhibitors using combination plots
-
additional information
-
molecular dynamics characterization of inhibitor adducts and structural variations induced by inhibitors
-
additional information
-
no inhibition by erythro-2-benzyl-2-methyl-3,4-epoxybutanoic acid
-
additional information
-
no inhibition by (2R,4R)-2-benzyl-3-methanesulfinylpropanoic acid
-
additional information
-
no inhibition by N-(aminocarbonyl)phenylalanine up to 3.6 mM
-
additional information
-
synthesis of cyclen-containing inhibitors specific for CPA
-
additional information
-
rational design of mechanism-based irreversible enzyme inhibitors, inhibition mechanism, overview
-
additional information
-
no or poor inhibition by soybean Kunitz trypsin inhibitor, E64, leupeptin, chymostatin, pepstatin A, N-tosyl-L-lysine chloromethyl ketone, N-tosyl-L-phenylalanine chloromethyl ketone, iodoacetic acid
-
additional information
-
no inhibition by pyrantel tartrate, 12.5% in the anthelmintic drug Banminth
-
additional information
-
sulfamide derivatives as transition state analogue inhibitors for carboxypeptidase A, synthesis, overview
-
additional information
-
O-glycosidase has no effect in monocyte-derived macrophages. CPVL in THP-1 and Jurkat cell lines are insensitive to treatment with a cocktail of O-glycosidase, N-glycosidase and endoglycosidase H
-
additional information
-
feeding of the laravae on broccoli foliage reduces the enzyme activity in the midgut
-
additional information
PMSF at 2 mM, E-64 at 0.001 mM and Mn2+, Ni2+, Ca2+ and Mg2+ at 1 mM have no effect on activity
-
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
Soybean trypsin inhibitor
-
leads to increased carboxypeptidase activity in larval midgut
-
proteoglycan
-
there is evidence indicating that the processing of pro-MC-CPA into active protease is dependent on proteoglycan
-
proteoglycan
-
there is evidence indicating that the processing of pro-MC-CPA into active protease is dependent on proteoglycan
-
proteoglycan
-
there is evidence indicating that the processing of pro-MC-CPA into active protease is dependent on proteoglycan
-
Trypsin
-
procarboxypeptidase A, pro CPA, is converted into the active form of CPA by trypsin
-
Trypsin
-
tryptic activation at a 1:10 (w/w) ratio for 60 min at room temperature
-
additional information
-
the capacity of poloxamer 188 to suppress aggregation of denaturated carboxypeptidase A is compared to that of polyethylenglycol
-
additional information
-
lipopolysaccharide has no effect on expression in monocyte-derived dendritic cells
-
additional information
-
infection with Ptf1a-expressing adenovirus vector induces the expression of the gene for carboxypeptidase in Pdx-1-positive pancreatic duct-derived (PPPD) cells
-
additional information
the triad for binding of the activation peptide consists of Asp, Phe, and Trp residues
-
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.372
3-(2-furyl)acryloyl-L-Phe-L-Ala
-
in 50 mM Tris-HCl, 100 mM NaCl, pH 7.5, at 37°C
0.0233
3-(2-furyl)acryloyl-L-Phe-L-Ile
-
in 50 mM Tris-HCl, 100 mM NaCl, pH 7.5, at 37°C
0.0194
3-(2-furyl)acryloyl-L-Phe-L-Leu
-
in 50 mM Tris-HCl, 100 mM NaCl, pH 7.5, at 37°C
0.04
3-(2-furyl)acryloyl-L-Phe-L-Met
-
in 50 mM Tris-HCl, 100 mM NaCl, pH 7.5, at 37°C
0.0556
3-(2-furyl)acryloyl-L-Phe-L-Phe
-
in 50 mM Tris-HCl, 100 mM NaCl, pH 7.5, at 37°C
0.0615
3-(2-furyl)acryloyl-L-Phe-L-Trp
-
in 50 mM Tris-HCl, 100 mM NaCl, pH 7.5, at 37°C
0.0573
3-(2-furyl)acryloyl-L-Phe-L-Val
-
in 50 mM Tris-HCl, 100 mM NaCl, pH 7.5, at 37°C
0.00923
Met-enkephalin-L-Arg-L-Phe
-
in 50 mM Tris-HCl, 100 mM NaCl, pH 7.5, at 37°C
0.49
O-(trans-p-chlorocinnamoyl)-L-beta-phenyllactate
-
pH 7.5, 25°C, mutant enzyme Y248A
5.8
O-(trans-p-chlorocinnamoyl)-L-beta-phenyllactate
-
pH 7.5, 25°C, mutant enzyme Y248F
120
O-(trans-p-chlorocinnamoyl)-L-beta-phenyllactate
-
pH 7.5, 25°C, wild-type enzyme
additional information
additional information
-
dissociation constant of enzyme GlyTyr complex: 0.001, no Michaelis-Menten kinetics with some substrates, larger substrates tend to have smaller Km-values than smaller substrates
-
additional information
additional information
-
derivation from classical Michalis-Menten kinetics with some substrates
-
additional information
additional information
-
approximations for several substrates: 0.01 mM
-
additional information
additional information
-
comparison of Km-values in crystals and in solution; comparison of Km-values of enzyme crystals and solution
-
additional information
additional information
-
comparison of affinities of various substituted metalloenzymes
-
additional information
additional information
-
Km values of immobilized enzyme generally higher than those in solution
-
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
24.3
3-(2-furyl)acryloyl-L-Phe-L-Ala
-
in 50 mM Tris-HCl, 100 mM NaCl, pH 7.5, at 37°C
12.4
3-(2-furyl)acryloyl-L-Phe-L-Ile
-
in 50 mM Tris-HCl, 100 mM NaCl, pH 7.5, at 37°C
13.4
3-(2-furyl)acryloyl-L-Phe-L-Leu
-
in 50 mM Tris-HCl, 100 mM NaCl, pH 7.5, at 37°C
23.9
3-(2-furyl)acryloyl-L-Phe-L-Met
-
in 50 mM Tris-HCl, 100 mM NaCl, pH 7.5, at 37°C
44.3
3-(2-furyl)acryloyl-L-Phe-L-Phe
-
in 50 mM Tris-HCl, 100 mM NaCl, pH 7.5, at 37°C
57.3
3-(2-furyl)acryloyl-L-Phe-L-Trp
-
in 50 mM Tris-HCl, 100 mM NaCl, pH 7.5, at 37°C
19.4
3-(2-furyl)acryloyl-L-Phe-L-Val
-
in 50 mM Tris-HCl, 100 mM NaCl, pH 7.5, at 37°C
1.45
Met-enkephalin-L-Arg-L-Phe
-
in 50 mM Tris-HCl, 100 mM NaCl, pH 7.5, at 37°C
0.11
O-(trans-p-chlorocinnamoyl)-L-beta-phenyllactate
-
pH 7.5, 25°C, wild-type enzyme
0.27
O-(trans-p-chlorocinnamoyl)-L-beta-phenyllactate
-
pH 7.5, 25°C, mutant enzyme Y248F
0.56
O-(trans-p-chlorocinnamoyl)-L-beta-phenyllactate
-
pH 7.5, 25°C, mutant enzyme Y248A
6.08
O-(trans-p-chlorocinnamoyl)-L-beta-phenyllactate
-
pH 7.5, 25°C, mutant enzyme Y248A
additional information
additional information
-
comparison of turnover numbers of enzyme crystals and solution
-
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
65
3-(2-furyl)acryloyl-L-Phe-L-Ala
-
in 50 mM Tris-HCl, 100 mM NaCl, pH 7.5, at 37°C
532
3-(2-furyl)acryloyl-L-Phe-L-Ile
-
in 50 mM Tris-HCl, 100 mM NaCl, pH 7.5, at 37°C
693
3-(2-furyl)acryloyl-L-Phe-L-Leu
-
in 50 mM Tris-HCl, 100 mM NaCl, pH 7.5, at 37°C
581
3-(2-furyl)acryloyl-L-Phe-L-Met
-
in 50 mM Tris-HCl, 100 mM NaCl, pH 7.5, at 37°C
797
3-(2-furyl)acryloyl-L-Phe-L-Phe
-
in 50 mM Tris-HCl, 100 mM NaCl, pH 7.5, at 37°C
93
3-(2-furyl)acryloyl-L-Phe-L-Trp
-
in 50 mM Tris-HCl, 100 mM NaCl, pH 7.5, at 37°C
338
3-(2-furyl)acryloyl-L-Phe-L-Val
-
in 50 mM Tris-HCl, 100 mM NaCl, pH 7.5, at 37°C
157
Met-enkephalin-L-Arg-L-Phe
-
in 50 mM Tris-HCl, 100 mM NaCl, pH 7.5, at 37°C
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.0000000048
(2S)-2-([hydroxy[(1R)-1-[[1-(1,4,7,10-tetraazacyclododecan-1-ylacetyl)-L-prolyl]amino]ethyl]phosphoryl]oxy)-3-phenylpropanoic acid
-
pH 7.5, 25°C
0.00000018
(2S)-2-([hydroxy[(1R)-1-[[N-(1,4,7,10-tetraazacyclododecan-1-ylacetyl)-b-alanyl]amino]ethyl]phosphoryl]oxy)-3-phenylpropanoic acid
-
pH 7.5, 25°C
0.0000000084
(2S)-2-([hydroxy[(1R)-1-[[N-(1,4,7,10-tetraazacyclododecan-1-ylacetyl)-L-alanyl]amino]ethyl]phosphoryl]oxy)-3-phenylpropanoic acid
-
pH 7.5, 25°C
0.000000059
(2S)-2-([hydroxy[(1R)-1-[[N-(1,4,7,10-tetraazacyclododecan-1-ylacetyl)-L-phenylalanyl]amino]ethyl]phosphoryl]oxy)-3-phenylpropanoic acid
-
pH 7.5, 25°C
0.000000082
(2S)-2-([hydroxy[(1R)-1-[[N-(1,4,7,10-tetraazacyclododecan-1-ylacetyl)glycyl]amino]ethyl]phosphoryl]oxy)-3-phenylpropanoic acid
-
pH 7.5, 25°C
0.000000077
(2S)-2-([hydroxy[(1S)-1-[[1-(1,4,7,10-tetraazacyclododecan-1-ylacetyl)-L-prolyl]amino]ethyl]phosphoryl]oxy)-3-phenylpropanoic acid
-
pH 7.5, 25°C
0.0000009
(2S)-2-([hydroxy[(1S)-1-[[N-(1,4,7,10-tetraazacyclododecan-1-ylacetyl)-b-alanyl]amino]ethyl]phosphoryl]oxy)-3-phenylpropanoic acid
-
pH 7.5, 25°C
0.00000009
(2S)-2-([hydroxy[(1S)-1-[[N-(1,4,7,10-tetraazacyclododecan-1-ylacetyl)-L-alanyl]amino]ethyl]phosphoryl]oxy)-3-phenylpropanoic acid
-
pH 7.5, 25°C
0.0000021
(2S)-2-([hydroxy[(1S)-1-[[N-(1,4,7,10-tetraazacyclododecan-1-ylacetyl)-L-phenylalanyl]amino]ethyl]phosphoryl]oxy)-3-phenylpropanoic acid
-
pH 7.5, 25°C
0.0000042
(2S)-2-([hydroxy[(1S)-1-[[N-(1,4,7,10-tetraazacyclododecan-1-ylacetyl)glycyl]amino]ethyl]phosphoryl]oxy)-3-phenylpropanoic acid
-
pH 7.5, 25°C
0.0000009
(2S)-2-[(hydroxy[(1R)-1-[(1,4,7,10-tetraazacyclododecan-1-ylacetyl)amino]ethyl]phosphoryl)oxy]-3-phenylpropanoic acid
-
pH 7.5, 25°C
0.19
(2S,3R)-2-benzyl-3,4-epoxybutanoic acid
-
pH 7.5, 25°C, substrate: hippuryl-L-Phe
0.00043
(R)-2-benzyl-5-nitro-4-oxopentanoic acid
-
in 0.05 M Tris/0.5 M NaCl buffer, pH 7.5
0.000000015 - 0.00000026
(S)-2-(Hydroxy-[(S)-1-[(S)-3-methyl-2-(2-1,4,7,10tetraaza-cyclododec-1-yl-acetylamino)-pentanoylamino]-ethyl]-phosphinoyloxy)-3-phenyl-propionic acid
0.00016
(S)-2-benzyl-5-nitro-4-oxopentanoic acid
-
in 0.05 M Tris/0.5 M NaCl buffer, pH 7.5
0.00529
2-(1-hydroxy-5-oxopyrrolidin-2-yl)-3-phenylpropanoic acid
-
25°C, limiting value for Ki-value at intermediate pH
0.00259
2-benzyl-3-[(difluoroacetyl)(hydroxy)amino]propanoic acid
-
25°C, limiting value for Ki-value at intermediate pH
0.012
2-benzyl-3-[(fluoroacetyl)(hydroxy)amino]propanoic acid
-
25°C, limiting value for Ki-value at intermediate pH
0.00139
2-benzyl-3-[formyl(hydroxy)amino]propanoic acid
-
25°C, limiting value for Ki-value at intermediate pH
0.009
2-benzyl-3-[hydroxy(methoxyacetyl)amino]propanoic acid
-
25°C, limiting value for Ki-value at intermediate pH
0.0994
2-benzyl-3-[hydroxy(methoxycarbonyl)amino]propanoic acid
-
25°C, limiting value for Ki-value at intermediate pH
0.00942
2-benzyl-3-[hydroxy(trifluoroacetyl)amino]propanoic acid
-
25°C, limiting value for Ki-value at intermediate pH
0.0002
2-benzyl-5,5,5-trifluoro-4-oxopentanoic acid
-
in 0.05 M Tris/0.5 M NaCl buffer, pH 7.5
0.015
2-benzyl-5-bromo-4-oxopentanoic acid
-
in 0.05 M Tris/0.5 M NaCl buffer, pH 7.5
0.0242