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Information on EC 3.4.24.55 - pitrilysin
for references in articles please use BRENDA:EC3.4.24.55
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EC Tree 3 Hydrolases
3.4 Acting on peptide bonds (peptidases)
3.4.24 Metalloendopeptidases
3.4.24.55 pitrilysin
IUBMB Comments
From the periplasmic space of Escherichia coli. Inhibited by EDTA and 1,10-phenanthroline; not thiol-dependent. Type example of peptidase family M16
The expected taxonomic range for this enzyme is: Bacteria, Archaea, Eukaryota
- 3.4.24.55
- metalloprotease
- metalloendopeptidase
- presequence
-
prep
- metallopeptidase
-
zinc-binding
-
insulin-degrading
- unstructured
- insulysin
-
oligopeptidase
- insulinase
- nardilysin
-
hxxeh
-
peptidasome
-
dibasic
- metalloendoprotease
- endoprotease
- b-chain
Reaction Schemes
showPreferential cleavage of -Tyr16-/- Leu- and -Phe25-/- Tyr-bonds of oxidized insulin B chain. Also acts on other substrates of less than 7 kDa such as insulin and glucagon
Synonyms
pitrilysin, ppbh4, escherichia coli protease iii, protease pi, more
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SYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
EC 3.4.99.44
-
-
formerly
-
Escherichia coli protease III
-
-
-
-
Pitrilysin
-
-
-
-
ppBH4
Protease Pi
-
-
-
-
Proteinase Pi
-
-
-
-
Proteinase, Escherichia coli metallo-, Pi
-
-
-
-
PTR
-
-
-
-
ppBH4
Halalkalibacterium halodurans H4
-
-
-
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REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
Preferential cleavage of -Tyr16-/- Leu- and -Phe25-/- Tyr-bonds of oxidized insulin B chain. Also acts on other substrates of less than 7 kDa such as insulin and glucagon
-
-
-
-
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
hydrolysis of peptide bond
-
-
-
-
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CAS REGISTRY NUMBER
COMMENTARY
81611-78-1
-
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SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
LITERATURE
COMMENTARY
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
(7-Methoxycoumarin-4-yl)acetyl-Nle-Ala-Val-Lys-Tyr-Leu-Asn-Ser-(2,4-dinitrophenyl)Lys-Leu-Asp-D-Lys + H2O
?
-
Substrates: -
Products: -
Products: -
?
(7-methoxycoumarin-4-yl)acetyl-Nle-Ala-Val-Lys-Tyr-Leu-Asn-Ser-Lys(2,4-dinitrophenyl)-Leu-Asp-D-Lys + H2O
?
-
Substrates: -
Products: -
Products: -
?
amyloid beta-peptide with mutations K16A/K28A + H2O
?
-
Substrates: cleavage site is identical to that of native amyloid beta-peptide
Products: -
Products: -
?
beta-amyloid + H2O
?
-
Substrates: 18% of the activity with beta-endorphin, major cleavage site His14-Gln15
Products: -
Products: -
?
beta-endorphin + H2O
?
-
Substrates: cleavage at Lys19-Asn20 bond. Residues Leu14, Val15 and Leu17 and region 22-26 are responsible for recognition by enzyme
Products: -
Products: -
?
calcitonin + H2O
?
-
Substrates: 3% of the activity with beta-endorphin
Products: -
Products: -
?
Substance P + H2O
?
-
Substrates: 10% of the activity with beta-endorphin
Products: -
Products: -
?
Vasoactive intestinal peptide + H2O
?
-
Substrates: 7.2% of the activity with beta-endorphin, major cleavage site Arg14-Lys15
Products: -
Products: -
?
dynorphin A fragment 1-13 + H2O
?
Halalkalibacterium halodurans
-
Substrates: cleavage at Phe4-Leu5, Leu5-Arg6, Arg6-Arg7, Arg7-Ile8
Products: -
Products: -
?
dynorphin A fragment 1-13 + H2O
?
Halalkalibacterium halodurans H4
-
Substrates: cleavage at Phe4-Leu5, Leu5-Arg6, Arg6-Arg7, Arg7-Ile8
Products: -
Products: -
?
Glucagon + H2O
?
-
Substrates: 8% of the activity with beta-endorphin
Products: -
Products: -
?
Insulin + H2O
Hydrolyzed insulin
-
Substrates: -
Products: -
Products: -
?
Insulin + H2O
Hydrolyzed insulin
-
Substrates: degradation in such a way that its receptor binding activity is rapidly lost but its precipitability in trichloroacetic acid is only slightly decreased
Products: -
Products: -
?
Insulin B-chain + H2O
?
-
Substrates: cleavage sites are Asn3-Gln4, His10-Leu11, Ala14-Leu15, Leu17-Val18, Gly23-Phe24, Phe24-Phe25, Phe25-Tyr26, the enzyme shares one of the only two cleavage sites with pitrilysin and 4 sites with insulin-destroying insulinase (EC 3.4.24.56)
Products: -
Products: -
?
Insulin B-chain + H2O
?
-
Substrates: small peptides down to 10 residues in length are cleaved more slowly, intact insulin is cleaved very slowly
Products: -
Products: -
?
Insulin B-chain + H2O
?
-
Substrates: 17% of the activity with beta-endorphin, major cleavage site Tyr16-Leu17
Products: -
Products: -
?
Insulin B-chain + H2O
?
Halalkalibacterium halodurans
-
Substrates: cleavage at Phe25-Tyr26, Tyr16-Leu17, His10-Leu11
Products: -
Products: -
?
Insulin B-chain + H2O
?
Halalkalibacterium halodurans H4
-
Substrates: cleavage at Phe25-Tyr26, Tyr16-Leu17, His10-Leu11
Products: -
Products: -
?
additional information
?
-
-
Substrates: larger proteins are accepted as substrates to a low extent
Products: -
Products: -
?
additional information
?
-
-
Substrates: prefers the cleavage of small polypeptides to the cleavage of proteins, inactive against synthetic amino acid derivatives of subtilisin, thermolysin, trypsin and chymotrypsin
Products: -
Products: -
?
additional information
?
-
-
Substrates: the activity of the enzyme is confined to substrates smaller than proteins
Products: -
Products: -
?
additional information
?
-
Halalkalibacterium halodurans
-
Substrates: no substrate: 4-nitroanilides of several amino acids tested, azocasein, bovine serum albumin
Products: -
Products: -
?
additional information
?
-
Halalkalibacterium halodurans H4
-
Substrates: no substrate: 4-nitroanilides of several amino acids tested, azocasein, bovine serum albumin
Products: -
Products: -
?
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METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Co2+
Mn2+
Zn2+
Zn2+
-
most effective metal ion in reactivation after inhibition by chelating agent
Zn2+
-
most effective metal ion in reactivation after inhibition by chelating agent
Zn2+
-
contains 1.02-1.14 mol of zinc per mol of enzyme (depending on mutant)
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INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
1,10-phenanthroline
-
Co2+, and to a lesser extent but at lower metal ion concentration Zn2+ restores activity
1,10-phenanthroline
-
Co2+, and to a lesser extent but at lower metal ion concentration Zn2+ restores activity
EDTA
-
Co2+, and to a lesser extent but at lower metal ion concentration Zn2+ restores activity
EDTA
-
Co2+, and to a lesser extent but at lower metal ion concentration Zn2+ restores activity
Zn2+
-
1 mM inhibits, but reactivates after inhibition with chelating agents
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DISEASE
TITLE OF PUBLICATION
LINK TO PUBMED
Alzheimer Disease
A common genetic system for functional studies of pitrilysin and related M16A proteases.
Insulinoma
The Mitochondrial Peptidase Pitrilysin Degrades Islet Amyloid Polypeptide in Beta-Cells.
pitrilysin deficiency
A common genetic system for functional studies of pitrilysin and related M16A proteases.
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KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.0077
(7-methoxycoumarin-4-yl)acetyl-Nle-Ala-Val-Lys-Tyr-Leu-Asn-Ser-Lys(2,4-dinitrophenyl)-Leu-Asp-D-Lys
-
-
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TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
2.9
(7-Methoxycoumarin-4-yl)acetyl-Nle-Ala-Val-Lys-Tyr-Leu-Asn-Ser-(2,4-dinitrophenyl)Lys-Leu-Asp-D-Lys
-
-
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SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
8
Halalkalibacterium halodurans
-
activity in sodium phosphate buffer is 3- to 4fold higher than in veronal or Tris/HCl buffer
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TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
45
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pI VALUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
-
-
-
brenda
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LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
Highest Expressing Human Cell Lines
Cell Line Links Show AA Sequence and Transmembrane Helices (5806 entries)
Longer loading times are possible. Please use the AA Sequence and Transmembrane Helices Search for a specific query.
Longer loading times are possible. Please use the AA Sequence and Transmembrane Helices Search for a specific query.
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PDB
SCOP
CATH
UNIPROT
ORGANISM
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MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
107000
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SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
monomer
monomer
Halalkalibacterium halodurans H4
-
1 * 46500, SDS-PAGE, 1 * 46585, calculated
-
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PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
N119A
-
promotion of yeast mating factor in heterologous expression is disabled
S117A/H118A/N119A
-
promotion of yeast mating factor in heterologous expression is disabled
S196A/K197A/F198A/S199A
-
promotion of yeast mating factor in heterologous expression is disabled
additional information
-
heterologous expression of enzyme in yeast, enzyme functionally substitutes for yeast Ax11p and Ste23p in pheromone production. Independent heterologous expression of N-terminal domain with amino acids 1-515 or C-terminal domain with amino acids 516-962 does not promote yeast mating. Co-expression of both domains restores yeast mating
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TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
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PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
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CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
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REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Swamy, K.H.; Goldberg, A.L.
Subcellular distribution of various proteases in Escherichia coli
J. Bacteriol.
149
1027-1033
1982
Escherichia coli
brenda
Finch, P.W.; Wilson, R.E.; Brown, K.; Hickson, I.D.; Emmerson, P.T.
Complete nucleotide sequence of the Escherichia coli ptr gene encoding protease III
Nucleic Acids Res.
14
7695-7703
1986
Escherichia coli
brenda
Ding, L.; Becker, A.B.; Suzuki, A.; Roth, R.A.
Comparison of the enzymatic and biochemical properties of human insulin-degrading enzyme and Escherichia coli protease III
J. Biol. Chem.
267
2414-2420
1992
Escherichia coli
brenda
Affholter, J.A.; Fried, V.A.; Roth, R.A.
Human insulin-degrading enzyme shares structural and functional homologies with E. coli protease III
Science
242
1415-1418
1988
Escherichia coli
brenda
Becker, A.B.; Roth, R.A.
An unusual active site identified in a family of zinc metalloendopeptidases
Proc. Natl. Acad. Sci. USA
89
3835-3839
1992
Escherichia coli
brenda
Anastasi, A.; Knight, C.G.; Barrett, A.J.
Characterization of the bacterial metalloendopeptidase pitrilysin by use of a continuous fluorescence assay
Biochem. J.
290
601-607
1993
Escherichia coli
brenda
Anastasi, A.; Barrett, A.J.
Pitrilysin
Methods Enzymol.
248
684-692
1995
Escherichia coli
brenda
Fricke, B.; Betz, R.; Friebe, S.
A periplasmic insulin-cleaving proteinase (ICP) from Acinetobacter calcoaceticus sharing properties with protease III from Escherichia coli and IDE from eucaryotes
J. Basic Microbiol.
35
21-31
1995
Acinetobacter calcoaceticus, Escherichia coli
brenda
Fricke, B.; Aurich, H.
Purification of a periplasmic insulin-cleaving proteinase from Acinetobacter calcoaceticus
Arch. Microbiol.
157
451-456
1992
Acinetobacter calcoaceticus
brenda
Alper, B.J.; Nienow, T.E.; Schmidt, W.K.
A common genetic system for functional studies of pitrilysin and related M16A proteases
Biochem. J.
398
145-152
2006
Escherichia coli
brenda
Dabonne, S.; Moallic, C.; Sine, J.P.; Niamke, S.; Dion, M.; Colas, B.
Cloning, expression and characterization of a 46.5-kDa metallopeptidase from Bacillus halodurans H4 sharing properties with the pitrilysin family
Biochim. Biophys. Acta
1725
136-143
2005
Halalkalibacterium halodurans, Halalkalibacterium halodurans H4
brenda
Cornista, J.; Ikeuchi, S.; Haruki, M.; Kohara, A.; Takano, K.; Morikawa, M.; Kanaya, S.
Cleavage of various peptides with pitrilysin from Escherichia coli: kinetic analyses using beta-endorphin and its derivatives
Biosci. Biotechnol. Biochem.
68
2128-2137
2004
Escherichia coli
brenda
Cornista, J.C.; Koga, Y.; Takano, K.; Kanaya, S.
Amyloidogenecity and pitrilysin sensitivity of a lysine-free derivative of amyloid beta-peptide cleaved from a recombinant fusion protein
J. Biotechnol.
122
186-197
2006
Escherichia coli
brenda
EXTERNAL LINKS (specific for EC-Number 3.4.24.55)
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