Information on EC 3.4.23.20 - Penicillopepsin

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The expected taxonomic range for this enzyme is: Penicillium

EC NUMBER
COMMENTARY hide
3.4.23.20
-
RECOMMENDED NAME
GeneOntology No.
Penicillopepsin
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
Hydrolysis of proteins with broad specificity similar to that of pepsin A, preferring hydrophobic residues at P1 and P1', but also cleaving Gly20-/-Glu in the B chain of insulin. Clots milk, and activates trypsinogen
show the reaction diagram
-
-
-
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
hydrolysis of peptide bond
-
-
aspartic endopeptidase
-
CAS REGISTRY NUMBER
COMMENTARY hide
9074-08-2
-
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
Penicillium duponti
Penicillium duponti K 1014
K 1014
-
-
Manually annotated by BRENDA team
Penicillium duponti K1014
strain K1014, thermophilic fungus
-
-
Manually annotated by BRENDA team
strain NRRL 905
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
(4-Nitro)Phe-Nle-Ala-Leu methyl ester + H2O
Nle-Ala-Leu methyl ester + (4-nitro)Phe
show the reaction diagram
-
-
-
-
Ac-(Ala)m-Lys-(NO2)Phe-(Ala)n amide + H2O
?
show the reaction diagram
-
-
-
-
-
Ac-(Ala)n-Lys-Nph-(Ala)m-amide + H2O
Ac-(Ala)n-Lys + Nph-(Ala)m-amide
show the reaction diagram
-
-
-
?
Ac-Ala-Ala-Ala-Lys-(NO2)Phe-Ala-Ala-amide + H2O
?
show the reaction diagram
Ac-Ala-Ala-Lys-(4-nitro)Phe-Ala-Ala amide + H2O
?
show the reaction diagram
-
-
-
-
-
Ac-Ala-Ala-Lys-(NO2)Phe-Ala-Ala-amide + H2O
?
show the reaction diagram
-
-
-
?
Ac-Ala-Ala-Lys-(NO2)Phe-Ala-amide + H2O
?
show the reaction diagram
-
-
-
?
Ac-Ala-Ala-Lys-(NO2)Phe-amide + H2O
?
show the reaction diagram
Ac-Ala-Ala-Lys-(p-NO2)Phe-Ala-Ala-NH2 + H2O
?
show the reaction diagram
-
-
-
?
Ac-Ala-Lys-(NO2)Phe-Ala-Ala-amide + H2O
?
show the reaction diagram
-
-
-
?
Ac-Ala-Lys-(NO2)Phe-Ala-amide + H2O
?
show the reaction diagram
Ac-Ala-Lys-(NO2)Phe-amide + H2O
?
show the reaction diagram
Ac-Lys 4-nitrophenyl amide + H2O
?
show the reaction diagram
-
-
-
-
-
Ac-Lys-(NO2)Phe- Ala-amide + H2O
?
show the reaction diagram
Ac-Lys-(NO2)Phe-Ala-Ala-amide + H2O
?
show the reaction diagram
-
-
-
?
Ac-Lys-(NO2)Phe-amide + H2O
?
show the reaction diagram
Ac-Xaa-Lys-(NO2)Phe-Ala-Ala amide + H2O
?
show the reaction diagram
-
-
-
-
-
B-chain of S-sulfo-insulin + H2O
?
show the reaction diagram
-
-
-
-
-
Bovine serum albumin + H2O
?
show the reaction diagram
-
cleaves 15% of the peptide bonds
-
-
-
Egg albumin + H2O
?
show the reaction diagram
FVNQHLCGSHLVEALYLVCGERGFFYTPKA + H2O
FVNQHLCGSHLVEALYLVCG + ERGFFYTPKA
show the reaction diagram
i.e. insulin B chain, cleavage site specificity
-
-
?
H-Leu-Ser-(4-nitro)Phe-Nle-Ala-Leu methyl ester + H2O
Nle-Ala-Leu methyl ester + Leu-Ser-(4-nitro)Phe
show the reaction diagram
-
-
-
-
Hemoglobin + H2O
?
show the reaction diagram
Leu-Ser-(4-nitro)Phe-Nle-Ala-Leu methyl ester + H2O
?
show the reaction diagram
-
-
-
-
-
Milk casein + H2O
?
show the reaction diagram
Pro-Thr-Glu-Phe-(4-nitro)Phe-Arg-Leu + H2O
Pro-Thr-Glu-Phe + (4-nitro)Phe-Arg-Leu
show the reaction diagram
-
-
-
-
trypsin inhibitor + H2O
trypsin inhibitor fragments
show the reaction diagram
-
substrate from Cucurbita maxima, specific cleavage of Leu7-Met8 bond at pH 3.3
-
-
?
Trypsinogen + H2O
?
show the reaction diagram
trypsinogen + H2O
trypsin + propeptide Val(Asn)4-Lys-OH
show the reaction diagram
substrate from Bos taurus, rapid activation
-
-
?
trypsinogen + H2O
trypsin + Val(Asn)4-Lys
show the reaction diagram
additional information
?
-
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
BaCl2
-
enhances milk clotting activity
CaCl2
-
enhances milk clotting activity
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
1,2-epoxy-3-(4-nitrophenoxy)propane
alpha-Diazo-p-bromoacetophenone
Penicillium duponti
-
in presence of Cu2+
Benzyloxycarbonyl-Gln-Tyr
-
-
Benzyloxycarbonyl-Glu
-
-
Benzyloxycarbonyl-Val-Tyr
-
-
Diazoacetyl DL-norleucine methyl ester
Diazoacetyl-DL-norleucine methyl ester
Diazoacetylglycine ethyl ester
Penicillium duponti
-
in presence of Cu2+
Difluorostatine- and difluorostatone-containing peptides
-
-
-
iodoacetic acid
-
-
isovaleryl-Val-statine-ethoxy
pepstatin analogue
isovaleryl-Val-Val-L-leucine phosphinic acid-L-3-phenyllactic acid methyl ester 1-L
-
-
-
isovaleryl-Val-Val-L-leucine phosphinic acid-L-3-phenyllactic acid methyl ester 2-L
-
-
-
isovaleryl-Val-Val-L-leucine phosphinic acid-L-3-phenyllactic acid methyl ester 3
-
-
-
Isovaleryl-Val-Val-statyl ethyl ester
-
-
Isovaleryl-Val-Val-statyl-Ala ethyl ester
-
-
K2PtCl6
-
partial
K3Fe(CN)6
-
-
KMnO4
Penicillium duponti
-
-
Leu-Gly-Leu
-
inhibits trypsinogen activation, activates cleavage of Leu-Tyr amide
methyl 10-hydroxy-6-[[N-(3-methylbutanoyl)valyl]amino]-9-(2-methylpropyl)-4,7-dioxo-11-oxa-3,8-diaza-10-phosphabicyclo[12.3.1]octadeca-1(18),14,16-triene-12-carboxylate 10-oxide
-
-
methyl cyclo[(2S)-2-[[(1R)-1-(N-(l-N-(3-methylbutanoyl)valyl-L-aspartyl)amino)-3-methylbutyl]hydroxyphosphinyloxy]-3-(3-aminomethyl)] phenylpropanoate
phosphonate-based macrocycle PPi4, macrocyclic pentapeptide inhibitor
-
methyl cyclo[(2S)-2-[[(1R)-1-(N-(l-N-(3-methylbutanoyl)valyl-L-aspartyl)amino)-3-methylbutyl]ydroxyphosphinyloxy]-3-(3-aminomethyl)] phenylpropanoate
-
N-bromosuccinimide
Penicillium duponti
-
-
Phosphorus-based peptide analogues
-
-
-
sodium lauryl sulfate
Penicillium duponti
-
-
Specific pepsin inhibitor produced by Streptomyces naniwaensis
Penicillium duponti
-
-
-
Streptomycin inhibitor
-
weak
-
additional information
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
Leu-Gly-Leu
-
inhibits trypsinogen activation, activates cleavage of Leu-Tyr amide
Reagents converting sulfhydryl groups to mercaptides
Penicillium duponti
-
activate
reduced glutathione
-
enhances milk clotting activity
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.075
Ac-Ala-Ala-Ala-Lys-(4-nitro)-Phe-Ala-Ala amide
-
pH 5.5 (pH-optimum for kcat)
0.39 - 0.68
Ac-Ala-Ala-Ala-Lys-(NO2)Phe-Ala-Ala-amide
0.25
Ac-Ala-Ala-Lys-(4-nitro)Phe amide
-
pH 4.5 (pH optimum for kcat)
0.078 - 0.44
Ac-Ala-Ala-Lys-(4-nitro)Phe-Ala-Ala amide
0.32 - 0.59
Ac-Ala-Ala-Lys-(NO2)Phe-Ala-Ala-amide
0.35 - 0.71
Ac-Ala-Ala-Lys-(NO2)Phe-Ala-amide
0.37 - 0.8
Ac-Ala-Ala-Lys-(NO2)Phe-amide
0.41
Ac-Ala-Lys-(4-nitro)Phe amide
-
pH 4.3 (optimum for kcat)
0.41 - 0.6
Ac-Ala-Lys-(NO2)Phe-Ala-Ala-amide
0.3 - 0.83
Ac-Ala-Lys-(NO2)Phe-Ala-amide
0.4 - 0.75
Ac-Ala-Lys-(NO2)Phe-amide
0.07
Ac-Gly-Lys-(4-nitro)Phe-Ala-Ala amide
-
pH 4.5
0.22
Ac-Lys 4-nitrophenyl amide
-
-
0.6
Ac-Lys-(4-nitro)Phe amide
-
pH 3.8-4.2 (optimum for kcat)
0.21 - 0.77
Ac-Lys-(NO2)Phe-Ala-Ala-amide
0.5 - 0.83
Ac-Lys-(NO2)Phe-Ala-amide
0.4 - 0.65
Ac-Lys-(NO2)Phe-amide
0.017
Ac-Val-Lys-(4-nitro)Phe-Ala amide
-
-
0.004 - 0.01
Leu-Ser-(4-nitro)Phe-Nle-Ala-Leu methyl ester
0.005
Pro-Thr-Glu-Phe-(4-nitro)Phe-Arg-Leu
-
-
0.0076
Trypsinogen
-
-
additional information
additional information
-
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.35 - 34
Ac-Ala-Ala-Ala-Lys-(NO2)Phe-Ala-Ala-amide
28.8 - 47
Ac-Ala-Ala-Lys-(4-nitro)Phe-Ala-Ala amide
45
Ac-Ala-Ala-Lys-(4-nitro)Phe-Ala-Ala-Ala amide
Penicillium janthinellum
-
pH 5.5 (pH-optimum for kcat)
0.3 - 40
Ac-Ala-Ala-Lys-(NO2)Phe-Ala-Ala-amide
0.09 - 15
Ac-Ala-Ala-Lys-(NO2)Phe-Ala-amide
0.0019 - 0.36
Ac-Ala-Ala-Lys-(NO2)Phe-amide
0.021
Ac-Ala-Lys-(4-nitro)Phe amide
Penicillium janthinellum
-
pH 4.3 (pH-optimum for kcat)
0.15 - 0.45
Ac-Ala-Lys-(NO2)Phe-Ala-Ala-amide
0.046 - 0.6
Ac-Ala-Lys-(NO2)Phe-Ala-amide
0.003 - 0.0054
Ac-Ala-Lys-(NO2)Phe-amide
0.003
Ac-Ala-Lys-Ala-(NO2)Phe-amide
Penicillium janthinellum
-
pH 5.0, 25C, mutant T219S
0.01
Ac-Lys 4-nitrophenyl amide
Penicillium janthinellum
-
pH 5.5
0.026
Ac-Lys-(4-nitro)Phe amide
Penicillium janthinellum
-
pH 3.8-4.2 (pH-optimum for kcat)
0.12 - 0.43
Ac-Lys-(NO2)Phe-Ala-Ala-amide
0.042 - 0.4
Ac-Lys-(NO2)Phe-Ala-amide
0.0016 - 0.005
Ac-Lys-(NO2)Phe-amide
5
bovine trypsinogen
Penicillium janthinellum
-
-
-
6.4 - 11.4
Leu-Ser-(4-nitro)Phe-Nle-Ala-Leu methyl ester
37.3
Pro-Thr-Glu-Phe-(4-nitro)Phe-Arg-Leu
Penicillium janthinellum
-
-
420
Trypsinogen
Penicillium janthinellum
P78735, Q9HEZ3
-
additional information
additional information
-
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.0008
isovaleryl-Val-Val-L-leucine phosphinic acid-L-3-phenyllactic acid methyl ester 1-L
-
-
-
0.0076
isovaleryl-Val-Val-L-leucine phosphinic acid-L-3-phenyllactic acid methyl ester 2-L
-
-
-
0.11
isovaleryl-Val-Val-L-leucine phosphinic acid-L-3-phenyllactic acid methyl ester 3
-
-
-
0.0000001
methyl cyclo[(2S)-2-[[(1R)-1-(N-(l-N-(3-methylbutanoyl)valyl-L-aspartyl)amino)-3-methylbutyl]ydroxyphosphinyloxy]-3-(3-aminomethyl)] phenylpropanoate
pH 4.6, macrocyclic pentapeptide inhibitor
0.00000001 - 0.0018
Pepstatin
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
additional information
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
2.6
-
bovine serum albumin
3 - 3.5
Penicillium duponti
-
hemoglobin, egg albumin
3
Penicillium duponti
-
hemoglobin, trypsinogen
3.4
-
trypsinogen
3.6
-
hydrolysis and transpeptidation of small substrates
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
55
Penicillium duponti
-
at pH 2.5, hemoglobin, 30 min incubation
60
Penicillium duponti
-
at pH 2.5, 10 min incubation
70
Penicillium duponti
-
at pH 3.6, hemoglobin, 30 min incubation
pI VALUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
3
below, penicillopepsin-JT1
3.3
Penicillium duponti
-
-
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
32000
-
Penicillium janthinellum
33400
-
x * 33400
33422
x * 33422, amino acid sequence calculation
33500
-
x * 33500
33700 - 34000
-
mass spectrometry
41000
Penicillium duponti
-
Penicillium duponti, gel filtration
additional information
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
additional information
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
glycoprotein
proteolytic modification
autoprocessing of the zymogen; autoprocessing of the zymogen releasing the propeptide Val(Asn)4-Lys; autoprocessing of the zymogen releasing the propeptide Val(Asn)4-Lys-OH
Crystallization/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
crystal structure at: 1.8 A
-
crystal structure in complex with inhibitor PPi3, monoclinic space group C2, a : 96.24 A, b : 46.47 A, c : 65.38 A, crystal structure in complex with inhibitor PPi4, monoclinic space group C2, a : 96.98 A, b : 46.65 A, c : 65.71 A
crystal structure of native penicillopepsin and of its complex with a synthetic analogue of the inhibitor pepstatin at 1.8 A resolution
-
crystallographic analysis of transition state mimics bound to penicillopepsin; difluorostatine- and difluorostatone-containing peptides
-
crystallographic analysis of transition state mimics bound to penicillopepsin; phosphorus-containing peptide analogues
-
purified penicillopepsin-JT1, free or bound to difluorostatine- and difluorostatone-containing peptides, X-ray diffraction structure determination and analysis at 0.95-2.8 A resolution
cocrystallized with inhibitor 1-L, space group C2, cell dimensions a 0 97.88 A, b = 46.64 A, c = 66.59 A
-
pH STABILITY
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
2 - 7
-
rapid loss of activity below pH 2.0 and above pH 7.0
30585
2.5 - 6
Penicillium duponti
-
30C, 20 h, stable
30595
2.5 - 6.5
Penicillium duponti
-
30C, 24 h, stable
30586
2.5
Penicillium duponti
-
65C, complete loss of activity after 15 min, 60C, complete loss of activity after 60 min
30586
3
-
37C, slow inactivation
30585
3.5 - 5.5
Penicillium duponti
-
60C, 1 h, stable
30586, 30595
4.9
-
55C, 1 h, stable
30585
6.1
-
37C, slow inactivation
30585
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
37
-
pH 3.0 or pH 6.1, slow inactivation
55
-
pH 4.9, 1 h, stable
60
Penicillium duponti
-
pH 3.5-5.5, 1 h, stable
70
Penicillium duponti
-
pH 4.5, 1 h, more than 65% of activity is retained
80
Penicillium duponti
-
pH 4.5, 10 min, complete inactivation
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
Room temperature, pH 4.9, several days
-
Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
penicillopepsin-JT1 to homogeneity; penicillopepsin-JT2
recombinant enzyme
-
Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
gene pepA, nucleotide sequence determined, inserted into expression vector pGPT-pyrG1, expressed in an aspartic proteinase-free strain of Aspergillus niger var. awamori
-
penicillopepsin-JT1, DNA and amino acid sequence determination and analysis; penicillopepsin-JT2, DNA and amino acid sequence determination and analysis; penicillopepsin-JT3, DNA and amino acid sequence determination and analysis
ENGINEERING
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
T219A
-
constructed by cassette insertion
-
T219G
-
constructed by cassette insertion
-
T219S
-
constructed by cassette insertion
-
T219V
-
constructed by cassette insertion
-
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
medicine
design of inhibitors with enhanced potency against proteolytic enzymes has many applications for treatment of human diseases