Any feedback?
Information on EC 3.4.21.89 - Signal peptidase I and Organism(s) Escherichia coli and UniProt Accession P00803
for references in articles please use BRENDA:EC3.4.21.89Please wait a moment until all data is loaded. This message will disappear when all data is loaded.
EC Tree
3.4.21.89 Signal peptidase ISpecify your search results
Word Map
- 3.4.21.89
- polyproteins
- lipoprotein
- preproteins
-
cleavable
- foot-and-mouth
-
unprocessed
-
dyad
-
membrane-spanning
- prolipoproteins
-
translocons
- pilins
-
uncleaved
- beta-lactamase
- drug development
- flavivirus
- ompa
-
nonstructural
-
cotranslationally
-
co-translational
-
sec-dependent
- globomycin
- presequence
-
papain-like
- prepeptide
-
polytopic
-
oligonucleotide-directed
- ns2b
-
signal-anchored
- pharmacology
- medicine
- analysis
The taxonomic range for the selected organisms is: Escherichia coli
The enzyme appears in selected viruses and cellular organisms
The enzyme appears in selected viruses and cellular organisms
Synonyms
signal peptidase, leader peptidase, spase, protease iv, signal peptidase i, spase i, type i signal peptidase, leader proteinase, plsp1, sec11, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
Bacterial leader peptidase 1
-
-
-
-
Escherichia coli leader peptidase
-
-
-
-
Eukaryotic signal peptidase
-
-
-
-
Eukaryotic signal proteinase
-
-
-
-
HOSP
-
-
-
-
Leader peptidase
-
-
-
-
Leader peptidase I
-
-
-
-
Leader peptide hydrolase
-
-
-
-
Leader proteinase
-
-
-
-
Peptidase, signal
-
-
-
-
Pilin leader peptidase
-
-
-
-
Prokaryotic leader peptidase
-
-
-
-
Prokaryotic signal peptidase
-
-
-
-
Prokaryotic signal proteinase
-
-
-
-
Propeptidase
-
-
-
-
Proteinase, eukaryotic signal
-
-
-
-
Proteinase, signal
-
-
-
-
PuIO prepilin peptidase
-
-
-
-
Signal peptidase
-
-
-
-
Signal peptide hydrolase
-
-
-
-
Signal peptide peptidase
-
-
-
-
Signalase
-
-
-
-
SPC
-
-
-
-
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
Cleavage of hydrophobic, N-terminal signal or leader sequences
mechanism
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
hydrolysis of peptide bond
-
-
-
-
CAS REGISTRY NUMBER
COMMENTARY
65979-36-4
-
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
(4-(4-dimethylaminophenylazo)benzoyl)-AGHDAHASET-(5-((2-aminoethyl)amino)-naphthalene-1-sulfonic acid) + H2O
(4-(4-dimethylaminophenylazo)benzoyl)-AGHDAHA + SET-(5-((2-aminoethyl)amino)-naphthalene-1-sulfonic acid)
-
-
-
?
mammalian cytochrome b(5) precursor + H2O
?
the processing can occur after almost complete exocytoplasmic translocation of the preprotein is accomplished
-
-
?
pre-maltose binding protein + H2O
maltose binding protein + signal peptide
the maltose binding protein (MBP) is mutated to introduce aromatic amino acids (tryptophan, tyrosine and phenylalanine) at P2' of the signal peptidase I cleavage sequence. All mutants with aromatic amino acids at P2' are exported less efficiently as indicated by a slight increase in precursor protein in vivo. Binding of LepB to peptides that encompass the MBP cleavage site are analysed using surface plasmon resonance. The presence of phenylalanine and tyrosine at P2', but not tryptophan, increase to a small extent the amount of preMBP in the sample
-
-
?
preprotein substrate PONA + H2O
protein substrate PONA + ?
-
-
?
(NO2)YFSASALA-KI-(2-aminobenzoyl)K-NH2 + H2O
(NO2)YFSASALA + KI-(2-aminobenzoyl)K-NH2
-
-
-
?
Acetyl-Trp-Leu-Val-Pro-norleucine-Leu-Ser-Phe-Ala-Ala-Glu-Gly-Asp-Asp-Pro-Ala-NH2 + H2O
Acetyl-Trp-Leu-Val-Pro-norleucine-Leu-Ser-Phe-Ala + Ala-Glu-Gly-Asp-Asp-Pro-Ala-NH2
-
-
-
?
Acetyl-Trp-Ser-Ala-Ser-Ala-Leu-Ala-Lys-Ile-4-methylcoumarin 7-amide + H2O
?
-
-
-
-
?
alkaline phosphatase signal peptide
?
-
clear evidence of a weak peptide-enzyme complex formation. The peptide adopts a U-turn shape originating from the proline residues within the primary sequence that is stabilized by its interaction with the peptidase and leaves key residues of the cleavage region exposed for proteolysis. In dodecylphosphocholine micelles the signal peptide also adopts a U-turn shape comparable with that observed in association with the enzyme. In both environments this conformation is stabilized by the signal peptide phenylalanine side chain-interaction with enzyme or lipid mimetic. In the presence of dodecylphosphocholine, the N-terminal core region residues of the peptide adopt a helical motif and are buried within the membrane. This is consistent with proteolysis of the preprotein occurring while the signal peptide remains in the bilayer and the enzyme active site functions at the membrane surface
-
-
?
alkaline phosphatase signal peptide fused to full-length mammalian cytochrome b5
cytochrome b5
-
amphipatic, chimeric cytochrome b5 precursor
-
?
M13 phage procoat protein + H2O
Free signal peptide + coat protein
-
hydrolysis of a single-Ala-+-Ala- bond, the term-+- depicts the point of cleavage
-
-
?
Phe-Ser-Ala-Ser-Ala-Leu-Ala-Lys-Ile + H2O
Phe-Ser-Ala-Ser-Ala-Leu-Ala-Lys-Ile + ?
-
-
-
-
?
Phe-Ser-Ala-Ser-Ala-Leu-Ala-Lys-Ile-NH2 + H2O
Phe-Ser-Ala-Ser-Ala-Leu-Ala + Lys-Ile-NH2
-
-
-
-
?
Precursor of the 23kd photosystem II protein + H2O
23kd Photosystem II protein + ?
-
-
-
-
?
Precursor of the leucine-binding protein + H2O
Leucine-binding protein + ?
-
-
-
-
?
Premaltose-binding protein + H2O
Maltose-binding protein + ?
-
-
-
-
?
Thylakoid lumen protein precursors + H2O
Thylakoid lumen protein + ?
-
-
-
-
?
Y-NO2-FSASALAKIK-2-aminobenzoyl-NH2 + H2O
Y-NO2-FSASALA + KIK-2-aminobenzoyl-NH2
-
-
-
-
?
YFSASALA-4-methylcoumarin-7-amide + H2O
YFSASALA + 7-amino-4-methylcoumarin
-
-
-
?
pro-ompA-nuclease + H2O
ompA-nuclease + ?
-
hybrid secretory precursor, best substrate in vitro, fusion protein consisting of the signal peptide of the E. coli outer membrane protein A OmpA attached to the Staphylococcus aureus nuclease A protein
-
?
pro-ompA-nuclease + H2O
ompA-nuclease + ?
-
hybrid secretory precursor, best substrate in vitro, fusion protein consisting of the signal peptide of the Escherichia coli outer membrane protein A OmpA attached to the Staphylococcus aureus nuclease A protein
-
?
signal peptides from preproteins + H2O
mature proteins
-
cleaves the precursors of many membrane and secreted proteins to their mature products, including most bacterial pre-proteins, yeast pre-acid phosphatase, honeybee pre-pro-mellitin, and human pre-hormones such as pre-pro-insulin, pre-growth hormone, preinterferon and others, can cleave several thylakoidal precursor proteins
-
?
signal peptides from preproteins + H2O
mature proteins
-
in vivo, type I signal peptidase is the principal peptidase responsible for signal peptide cleavage as pre-proteins of a number of exported proteins, proteins designed for transport across the cytoplasmic membrane are generally synthesised as precursors with cleavable signal peptides in the cytoplasm, the signal peptides targets the pre-proteins to the respective translocase, during or shortly after translocation across the cytoplasmic membrane, the signal peptide is enzymatically removed
-
?
signal peptides from preproteins + H2O
mature proteins
-
in vivo, type I signal peptidase is the principal peptidase responsible for signal peptide cleavage as pre-proteins of a number of exported proteins, proteins designed for transport across the cytoplasmic membrane are generally synthesised as precursors with cleavable signal peptides in the cytoplasm, the signal peptides targets the pre-proteins to the respective translocase, during or shortly after translocation across the cytoplasmic membrane, the signal peptide is enzymatically removed
-
?
signal peptides from preproteins + H2O
mature proteins
-
in vivo, type I signal peptidase is the principal peptidase responsible for signal peptide cleavage as pre-proteins of a number of exported proteins, proteins designed for transport across the cytoplasmic membrane are generally synthesised as precursors with cleavable signal peptides in the cytoplasm, the signal peptides targets the pre-proteins to the respective translocase, during or shortly after translocation across the cytoplasmic membrane, the signal peptide is enzymatically removed
-
?
signal peptides from preproteins + H2O
mature proteins
-
key role in the protein secretary pathway
-
?
additional information
?
-
SPase I is an essential membrane-bound endopeptidase with a unique Ser/Lys dyad mechanism
-
-
?
additional information
?
-
-
SPase I is an essential membrane-bound endopeptidase with a unique Ser/Lys dyad mechanism
-
-
?
additional information
?
-
cleavage site specificity of Escherichia coli SPase I, overview. Cobstruction of different signal peptides of MBP and binding analysis with the enzyme
-
-
?
additional information
?
-
-
cleavage site specificity of Escherichia coli SPase I, overview. Cobstruction of different signal peptides of MBP and binding analysis with the enzyme
-
-
?
additional information
?
-
signal peptidase I processes secretory signal sequences. Selection for and against specific amino acids occurs at the second position of mature protein. The enzyme shows preference for the presence of acidic residues at second position of the mature protein (P2'), and a complete absence of aromatic amino acids at the same position. Substrate specificity and in silico prediction of signal peptidase I cleavage sites, overview
-
-
?
additional information
?
-
-
cleavage of E. coli enzyme requires a small residue at-1 and a small or aliphatic residue at-3, presence of a helix breaker allows the pre-protein to bind with higher affinity, signal peptides that include a Pro residue at position-1 are not cleaved in E. coli
-
-
?
additional information
?
-
-
minimum sequence of a substrate hydrolyzed is the pentapeptide Ala-Leu-Ala-+-Lys-Ile, the term-+- depicts the point of cleavage
-
-
?
additional information
?
-
-
cleavable pre-proteins must have small residues at-1 and a small or aliphatic residue at-3 (with respect to the cleavage site)
-
-
?
additional information
?
-
-
family of serine proteases that lacks a complete catalytic triad
-
-
?
additional information
?
-
-
a typical signal sequence is 15-25 amino acids long, it has a tripartite structure consisting of a positively charged NH2-terminal region (n-region, 1-5 amino acids), a central hydrophobic core (h-region, 7-15 amino acids) probably arranged in a alpha-helix, and, separated by an alpha-helix breaking Pro or Gly, the more polar part (c-region, 3-7 amino acids), representing half of the cleavage site
-
-
?
additional information
?
-
-
specificity of the thylakoid processing peptidase and E. coli leader peptidase are identical
-
-
?
additional information
?
-
-
requirements for substrate recognition by bacterial leader peptidase
-
-
?
additional information
?
-
-
although the enzyme is unable to cleave an X-Pro bond, a proline at-1 does not prevent the enzyme from recognizing the normal processing site
-
-
?
additional information
?
-
-
specificity: leader peptidase 1 cleaves the majority of the preproteins destined to the cell surface
-
-
?
additional information
?
-
-
the better peptide substrates are those that are able to adopt folded structures
-
-
?
additional information
?
-
-
secretory proteins are synthesized with an aminoterminal extension, the signal peptide, signal peptidases are required for the removal of these extensions
-
?
additional information
?
-
-
the physiological role is to release exported proteins from the membrane by removing the leader sequence
-
-
?
additional information
?
-
-
the enzyme removes amino-terminal leader peptides from exported proteins after they have crossed the plasma membrane
-
-
?
additional information
?
-
-
in addition to naturally occuring precursor protein substrates, signal peptidase can process short, synthetic peptide substrates based on the cleavage site region of pre-maltose binding protein and M13 procoat, minimum length for cleavage of peptide substrates is 5 residues, -3 to + 2 of the pre-maltose binding protein, indicating that the recognition sequence for signal peptidase lies between the -3 and +2 position
-
?
additional information
?
-
-
cleaves the signal peptide of the GST-SP-AP-His construct into two fragments, the GST protein plus the signal peptide (28 kDa), and the first 30 amino acids of the mature region 6-His-tagged (4 kDa)
-
-
?
additional information
?
-
-
substrate binding to SPase I proceeds consistent with induced-fit recognition. Residues Gln85, Ile86, Ser88, Gly89, Ser90, Met91, Leu95, Val132, Asp142, Ile144, and Lys145 in addition to Ile80, Glu82, Ile101, Gly109, and Lys134, are responsive to signal peptide binding and alter conformation
-
-
?
additional information
?
-
-
binding of the signal petide to the sinal peptidase leads to weak peptide-enzyme complex formation. The peptide adopts a U-turn shape originating from the proline residues within the primary sequence that is stabilized by its interaction with the peptidase and leaves key residues of the cleavage region exposed for proteolysis. In dodecylphosphocholine micelles the signal peptide also adopts a U-turn shape comparable with that observed in association with the enzyme. In both environments this conformation is stabilized by the signal peptide phenylalanine side chain-interaction with enzyme or lipid mimetic. In the presence of dodecylphosphocholine, the N-terminal core region residues of the peptide adopt a helical motif are buried within the membrane
-
-
?
NATURAL SUBSTRATE
NATURAL 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
signal peptides from preproteins + H2O
mature proteins
-
in vivo, type I signal peptidase is the principal peptidase responsible for signal peptide cleavage as pre-proteins of a number of exported proteins, proteins designed for transport across the cytoplasmic membrane are generally synthesised as precursors with cleavable signal peptides in the cytoplasm, the signal peptides targets the pre-proteins to the respective translocase, during or shortly after translocation across the cytoplasmic membrane, the signal peptide is enzymatically removed
-
?
signal peptides from preproteins + H2O
mature proteins
-
in vivo, type I signal peptidase is the principal peptidase responsible for signal peptide cleavage as pre-proteins of a number of exported proteins, proteins designed for transport across the cytoplasmic membrane are generally synthesised as precursors with cleavable signal peptides in the cytoplasm, the signal peptides targets the pre-proteins to the respective translocase, during or shortly after translocation across the cytoplasmic membrane, the signal peptide is enzymatically removed
-
?
signal peptides from preproteins + H2O
mature proteins
-
in vivo, type I signal peptidase is the principal peptidase responsible for signal peptide cleavage as pre-proteins of a number of exported proteins, proteins designed for transport across the cytoplasmic membrane are generally synthesised as precursors with cleavable signal peptides in the cytoplasm, the signal peptides targets the pre-proteins to the respective translocase, during or shortly after translocation across the cytoplasmic membrane, the signal peptide is enzymatically removed
-
?
signal peptides from preproteins + H2O
mature proteins
-
key role in the protein secretary pathway
-
?
additional information
?
-
-
the physiological role is to release exported proteins from the membrane by removing the leader sequence
-
-
?
additional information
?
-
-
the enzyme removes amino-terminal leader peptides from exported proteins after they have crossed the plasma membrane
-
-
?
additional information
?
-
-
in addition to naturally occuring precursor protein substrates, signal peptidase can process short, synthetic peptide substrates based on the cleavage site region of pre-maltose binding protein and M13 procoat, minimum length for cleavage of peptide substrates is 5 residues, -3 to + 2 of the pre-maltose binding protein, indicating that the recognition sequence for signal peptidase lies between the -3 and +2 position
-
?
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
(5S,6S)-3-[(2-aminoethyl)sulfanyl]-6-[(1R)-1-hydroxyethyl]-7-oxo-4-thia-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid
IC50 is 0.00063 mg/l
(5S,6S)-3-[[2-(carbamoyloxy)ethyl]sulfanyl]-6-[(1R)-1-hydroxyethyl]-7-oxo-4-thia-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid
IC50 is 0.00096 mg/l
(5S,6S)-3-[[2-(dimethylamino)ethyl]sulfanyl]-6-[(1R)-1-hydroxyethyl]-7-oxo-4-thia-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid
IC50 is 0.00395 mg/l
(5S,6S)-3-[[3-(dimethylcarbamoyl)cyclopentyl]sulfanyl]-6-[(1R)-1-hydroxyethyl]-7-oxo-4-thia-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid
IC50 is 0.00122 mg/l
(5S,6S)-6-[(1R)-1-hydroxyethyl]-3-([2-[(iminomethyl)amino]ethyl]sulfanyl)-7-oxo-4-thia-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid
IC50 is 0.00104 mg/l
(5S,6S)-6-[(1R)-1-hydroxyethyl]-3-[(2-hydroxyethyl)sulfanyl]-7-oxo-4-thia-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid
IC50 is 0.00149 mg/l
(5S,6S)-6-[(1R)-1-hydroxyethyl]-3-[[2-(methylamino)ethyl]sulfanyl]-7-oxo-4-thia-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid
IC50 is 0.00637 mg/l
(5S,6S)-6-[(1R)-1-hydroxyethyl]-7-oxo-3-[[(1R)-3-oxocyclopentyl]sulfanyl]-4-thia-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid
IC50 is 0.00116 mg/l
(5S,6S)-6-[(1R)-1-hydroxyethyl]-7-oxo-3-[[(3R)-pyrrolidin-3-yl]sulfanyl]-4-thia-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid
IC50 is 0.00175 mg/l
(5S,6S)-6-[(1R)-1-hydroxyethyl]-7-oxo-3-[[(3S)-pyrrolidin-3-yl]sulfanyl]-4-thia-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid
IC50 is 0.00080 mg/l
(5S,6S)-6-[(1R)-1-hydroxyethyl]-7-oxo-3-[[2-(pyridin-2-yl)ethyl]sulfanyl]-4-thia-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid
IC50 is 0.00131 mg/l
(5S,6S)-6-[(2R)-2-hydroxypropyl]-7-oxo-4-thia-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid
IC50 is 0.00299 mg/l
arylomycin
while arylomycins have activity against a variety of Gram-positive and Gram-negative bacteria, mutations within SPase that ablate a hydrogen bond limit their spectrum
-
arylomycin A2
a lipohexapeptide-based natural product, inhibits SPase I by binding to non-overlapping subsites near the catalytic center in a noncovalent manner, binding mode, overview
BAL0019193
a morpholino-beta-sultam derivative, inhibits SPase I by binding to non-overlapping subsites near the catalytic center in a noncovalent manner, binding mode, overview
prop-2-en-1-yl (5S,6S)-6-[(2R)-2-hydroxypropyl]-7-oxo-4-thia-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate
crystal structure of enzyme-bound 1, PDB ID 1B12
arylomycin A-C16
-
inhibition of enzyme results in an insufficient flux of proteins through the secretion pathway leading to mislocalization of proteins. Inhibition results in synergistic sensitivity when combined with an aminoglycoside
Bromosuccinimide
-
inactivation by modification of tryptophan residues 300 and 310
Leader peptide of bacteriophage procoat
-
inhibits cleavage of M13 procoat or pre-maltose-binding protein
-
N-hexadecanoyl-N-methylserylalanyl-N-[13-carboxy-3-[(6-deoxyhexopyranosyl)oxy]-4,18-dihydroxy-10-methyl-8,11-dioxo-9,12-diazatricyclo[13.3.1.12,6]icosa-1(19),2(20),3,5,15,17-hexaen-7-yl]-N-methylglycinamide
-
IC50: 190 nM
N-methyl-N-(12-methyltridecanoyl)serylalanyl-N-[13-carboxy-3-[(6-deoxyhexopyranosyl)oxy]-18-hydroxy-10-methyl-8,11-dioxo-9,12-diazatricyclo[13.3.1.12,6]icosa-1(19),2(20),3,5,15,17-hexaen-7-yl]-N-methylglycinamide
-
IC50: 110 nM
N-methyl-N-(12-methyltridecanoyl)serylalanyl-N-[13-carboxy-3-[(6-deoxyhexopyranosyl)oxy]-4,18-dihydroxy-10-methyl-8,11-dioxo-9,12-diazatricyclo[13.3.1.12,6]icosa-1(19),2(20),3,5,15,17-hexaen-7-yl]-N-methylglycinamide
-
IC50: 110 nM
N-methyl-N-(13-methyltetradecanoyl)serylalanyl-N-[13-carboxy-3-[(6-deoxyhexopyranosyl)oxy]-18-hydroxy-10-methyl-8,11-dioxo-9,12-diazatricyclo[13.3.1.12,6]icosa-1(19),2(20),3,5,15,17-hexaen-7-yl]-N-methylglycinamide
-
IC50: 130 nM
N-methyl-N-(14-methylpentadecanoyl)serylalanyl-N-[13-carboxy-3-[(6-deoxyhexopyranosyl)oxy]-18-hydroxy-10-methyl-8,11-dioxo-9,12-diazatricyclo[13.3.1.12,6]icosa-1(19),2(20),3,5,15,17-hexaen-7-yl]-N-methylglycinamide
-
IC50: 130 nM
N-methyl-N-(14-methylpentadecanoyl)serylalanyl-N-[13-carboxy-3-[(6-deoxyhexopyranosyl)oxy]-4,18-dihydroxy-10-methyl-8,11-dioxo-9,12-diazatricyclo[13.3.1.12,6]icosa-1(19),2(20),3,5,15,17-hexaen-7-yl]-N-methylglycinamide
-
IC50: 170 nM
N-methyl-N-pentadecanoylserylalanyl-N-[13-carboxy-3-[(6-deoxyhexopyranosyl)oxy]-18-hydroxy-10-methyl-8,11-dioxo-9,12-diazatricyclo[13.3.1.12,6]icosa-1(19),2(20),3,5,15,17-hexaen-7-yl]-N-methylglycinamide
-
IC50: 130 nM
N-methyl-N-tetradecanoylserylalanyl-N-[13-carboxy-3-[(6-deoxyhexopyranosyl)oxy]-18-hydroxy-10-methyl-8,11-dioxo-9,12-diazatricyclo[13.3.1.12,6]icosa-1(19),2(20),3,5,15,17-hexaen-7-yl]-N-methylglycinamide
-
IC50: 110 nM
pre-protein including a proline at the +1 position
-
not cleaved, act as competitive inhibitors
-
additional information
beta-lactam antibiotics, one of the most important class of human therapeutics, act via the inhibition of penicillin-binding proteins (PBPs). Bacterial type I signal peptidase is evolutionarily related to the PBPs, but the stereochemistry of its substrates and its catalytic mechanism suggest that beta-lactams with the 5S stereochemistry, as opposed to the 5R stereochemistry of the traditional beta-lactams, are required for inhibition. Synthesis and evaluation of a variety of 5S penem derivatives and identify several with promising activity against both a Gram-positive and a Gram-negative bacterial pathogen, overview. The 5S beta-lactams possess significant antibacterial activity
-
additional information
several classes of inhibitors exist for SPase: krisynomycin and the arylomycin family represent natural product inhibitors, whereas 5S penems peptide substrate mimics and a beta-aminoketone are synthetic inhibitors
-
additional information
-
but site-directed mutagenesis implicates a Ser/Lys catalytic dyad in activity
-
additional information
-
but site-directed mutagenesis implicates a Ser/Lys catalytic dyad in activity
-
additional information
-
but site-directed mutagenesis implicates a Ser/Lys catalytic dyad in activity
-
additional information
-
unaffected by inhibitors of most serine peptidases
-
additional information
-
scarcely inhibited by treatment with: N-acetylimidazole, iodoacetic acid, 5,5'-dithiobis(2-nitrobenzoic acid), succinic anhydride, 2,4,6-trinitrobenzenesulfonate
-
additional information
-
a mutant maltose-binding protein species with Pro at the +1 position interferes with the activity of signal peptidase in vivo, the mutant protein is not processed at either the normal site or an upstream alternate site previously identified, induced synthesis of this protein is inhibitory to cell growth and causes a pleiotrophic defect in processing of all nonlipoprotein precursors examined
-
additional information
-
not inhibited by any commercially available peptidase inhibitor including o-phenanthroline, ethylenediamine tetraacetic acid, phosphoramidon, 2,6-pyridine dicarboxylic acid, bestatin, tosyl-amido-2-phenylethyl chloromethyl ketone, 1-chloro-3-tosylamido-7-amino-2-heptanone hydrochloride, phenylmethylsulfonyl fluoride, 4-(amidinophenyl)methanesulfonyl fluoride, N-carbobenzyloxy-L-phenylalanyl chloromethyl ketone, dichloroisocoumarin, elastatinal, aprotinin, chymostatin, leupeptin, antipain dihydrochloride, iodoacetamide, N-ethyl maleimide, L-trans-epoxysuccinyl-leucylamido (4-guanidino) butane, 1,2-epoxy-3-(p nitrophenoxy)propane, pepstatin, and diaxoacetyl-DL-norleucine methyl ester
-
additional information
-
not inhibited by classical protease inhibitors such as phenylmethyl sulfonyl fluoride, tosyl-amido-2-phenylethylchloromethylketone, EDTA, o-phenanthroline, N-ethylmaleimide, dinitrophenol, carboxyphenanthroline, or 2,6-pyridinecarboxylic acid
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
dodecylphosphocholine
-
at 37°C, degradation occurs to a lesser extent in dodecylphosphocholine micelles than in Triton X-100 or n-octyl-beta-D-glucopyranoside
phosphatidylethanolamine
-
is required to maintain activity of the membrane-incorporated signal-peptidase (full-length signal peptidase I incoporated into phospholipid vesicles). Maximal activity is achieved at about 55% phosphatidylethanolamine
additional information
-
no significant difference in expression levels in the presence and absence of deuterium oxide. Elevated temperature enhances enzyme degradation, at 37°C, the protein is autolysed and degraded more than at 22°C
-
Triton X-100
-
stimulates activity with pro-OmpA-nuclease A or a peptide substrate
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.05
alkaline phosphatase signal peptide fused to full-length mammalian cytochrome b5
-
pH 7.5, 37°C
-
additional information
additional information
-
effect of the length of the polypeptide substrate in the Km-value
-
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
11
alkaline phosphatase signal peptide fused to full-length mammalian cytochrome b5
-
pH 7.5, 37°C
-
additional information
additional information
-
effect of the length of the polypeptide chain of substrates on the turnover number
-
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.000158
N-hexadecanoyl-N-methylserylalanyl-N-[13-carboxy-3-[(6-deoxyhexopyranosyl)oxy]-4,18-dihydroxy-10-methyl-8,11-dioxo-9,12-diazatricyclo[13.3.1.12,6]icosa-1(19),2(20),3,5,15,17-hexaen-7-yl]-N-methylglycinamide
-
-
0.00005
N-methyl-N-(12-methyltridecanoyl)serylalanyl-N-[13-carboxy-3-[(6-deoxyhexopyranosyl)oxy]-18-hydroxy-10-methyl-8,11-dioxo-9,12-diazatricyclo[13.3.1.12,6]icosa-1(19),2(20),3,5,15,17-hexaen-7-yl]-N-methylglycinamide
-
-
0.00011
N-methyl-N-(12-methyltridecanoyl)serylalanyl-N-[13-carboxy-3-[(6-deoxyhexopyranosyl)oxy]-4,18-dihydroxy-10-methyl-8,11-dioxo-9,12-diazatricyclo[13.3.1.12,6]icosa-1(19),2(20),3,5,15,17-hexaen-7-yl]-N-methylglycinamide
-
-
0.000058
N-methyl-N-(14-methylpentadecanoyl)serylalanyl-N-[13-carboxy-3-[(6-deoxyhexopyranosyl)oxy]-18-hydroxy-10-methyl-8,11-dioxo-9,12-diazatricyclo[13.3.1.12,6]icosa-1(19),2(20),3,5,15,17-hexaen-7-yl]-N-methylglycinamide
-
-
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.00019
N-hexadecanoyl-N-methylserylalanyl-N-[13-carboxy-3-[(6-deoxyhexopyranosyl)oxy]-4,18-dihydroxy-10-methyl-8,11-dioxo-9,12-diazatricyclo[13.3.1.12,6]icosa-1(19),2(20),3,5,15,17-hexaen-7-yl]-N-methylglycinamide
Escherichia coli
-
IC50: 190 nM
0.00011
N-methyl-N-(12-methyltridecanoyl)serylalanyl-N-[13-carboxy-3-[(6-deoxyhexopyranosyl)oxy]-18-hydroxy-10-methyl-8,11-dioxo-9,12-diazatricyclo[13.3.1.12,6]icosa-1(19),2(20),3,5,15,17-hexaen-7-yl]-N-methylglycinamide
Escherichia coli
-
IC50: 110 nM
0.00011
N-methyl-N-(12-methyltridecanoyl)serylalanyl-N-[13-carboxy-3-[(6-deoxyhexopyranosyl)oxy]-4,18-dihydroxy-10-methyl-8,11-dioxo-9,12-diazatricyclo[13.3.1.12,6]icosa-1(19),2(20),3,5,15,17-hexaen-7-yl]-N-methylglycinamide
Escherichia coli
-
IC50: 110 nM
0.00013
N-methyl-N-(13-methyltetradecanoyl)serylalanyl-N-[13-carboxy-3-[(6-deoxyhexopyranosyl)oxy]-18-hydroxy-10-methyl-8,11-dioxo-9,12-diazatricyclo[13.3.1.12,6]icosa-1(19),2(20),3,5,15,17-hexaen-7-yl]-N-methylglycinamide
Escherichia coli
-
IC50: 130 nM
0.00013
N-methyl-N-(14-methylpentadecanoyl)serylalanyl-N-[13-carboxy-3-[(6-deoxyhexopyranosyl)oxy]-18-hydroxy-10-methyl-8,11-dioxo-9,12-diazatricyclo[13.3.1.12,6]icosa-1(19),2(20),3,5,15,17-hexaen-7-yl]-N-methylglycinamide
Escherichia coli
-
IC50: 130 nM
0.00017
N-methyl-N-(14-methylpentadecanoyl)serylalanyl-N-[13-carboxy-3-[(6-deoxyhexopyranosyl)oxy]-4,18-dihydroxy-10-methyl-8,11-dioxo-9,12-diazatricyclo[13.3.1.12,6]icosa-1(19),2(20),3,5,15,17-hexaen-7-yl]-N-methylglycinamide
Escherichia coli
-
IC50: 170 nM
0.00013
N-methyl-N-pentadecanoylserylalanyl-N-[13-carboxy-3-[(6-deoxyhexopyranosyl)oxy]-18-hydroxy-10-methyl-8,11-dioxo-9,12-diazatricyclo[13.3.1.12,6]icosa-1(19),2(20),3,5,15,17-hexaen-7-yl]-N-methylglycinamide
Escherichia coli
-
IC50: 130 nM
0.00011
N-methyl-N-tetradecanoylserylalanyl-N-[13-carboxy-3-[(6-deoxyhexopyranosyl)oxy]-18-hydroxy-10-methyl-8,11-dioxo-9,12-diazatricyclo[13.3.1.12,6]icosa-1(19),2(20),3,5,15,17-hexaen-7-yl]-N-methylglycinamide
Escherichia coli
-
IC50: 110 nM
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
8.5 - 9
-
maximal processing rates at pH 8.5 and above, 90% activity at neutral pH
additional information
pH RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
4.5 - 9
-
20% of maximal activity at pH 4.5, half-maximal activity at pH 6.5, 90% of maximal activity at pH 7.0
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
TEMPERATURE RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
transcytoplasmic signal peptidase anchored to the inner membrane
transcytoplasmic signal peptidase anchored to the inner membrane
additional information
-
a favorable interaction can occur between the hydrophobic surface of SPase I and the bacterial membrane
-
-
amino-termial domain facing the cytoplasm and its carboxyl terminus facing the periplasm, only the second of three apolar domains has an essential function in membrane assembly
-
-
it is anchored to the membrane by two transmembrane segments and is oriented with a short domain facing the cytoplasm and a large carboxyl-terminal domain exposed to the periplasmic space
-
the enzyme spans the membrane twice, with its large carboxyl-terminal domain protruding into the periplasm
-
the catalytic domain extends into the periplasmic space and is anchored to the membrane by two transmembrane segments located at the N-terminal end of the protein
-
signal peptide substrate remains in the bilayer and the enzyme active site functions at the membrane surface
-
membrane-bound, carboxyterminal catalytic region which resides in the periplasmic space
-
the active site o the enzyme is located in the periplasm
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
evolution
malfunction
potential consequences of SPase inhibition on bacterial virulence, overview. The antivirulence effects of inhibiting SPase are expected due to the many proteinaceous virulence factors that rely on SPase for processing into functional forms. SPase inhibition results in the accumulation of unprocessed proteins in the cytoplasmic membrane, which eventually causes it to lose its integrity and leads to cell death
physiological function
evolution
bacterial type I signal peptidase is evolutionarily related to the penicillin-binding proteins (PBPs)
evolution
Escherichia coli and Bacillus subtilis primarily express a signal peptidase I that contains a serine-lysine catalytic dyad, whilst those of archaeal and eukaryotic origin generally have a serine-histidine catalytic dyad
physiological function
exported proteins require an N-terminal signal peptide to direct them from the cytoplasm to the periplasm. Once the protein has been translocated across the cytoplasmic membrane, the signal peptide is cleaved by a signal peptidase, allowing the remainder of the protein to fold into its mature state in the periplasm. Signal peptidase I (LepB) cleaves non-lipoproteins and recognises the sequence Ala-X-Ala. Amino acids present at the N-terminus of mature, exported proteins affect the efficiency at which the protein is exported
physiological function
signal peptides direct proteins from the cytoplasm to the periplasm. These N-terminal peptides are cleaved upon entry to the periplasm by either signal peptidase I, or signal peptidase II for lipoproteins. Signal peptidase I is a serine protease that has either a serine-lysine or serine-histidine catalytic dyad present in the active site. The recognition site for signal peptide cleavage by signal peptidase I has been defined primarily by an Ala-X-Ala motif at the C-terminal end of the signal peptide, one amino acid away from the cleavage site
physiological function
type I signal peptidase (SPase) is an essential part of the secretion apparatus. Its proteolytic activity is required to release proteins from their N-terminal leader sequence, which remain membrane bound after the preprotein translocates across the cytoplasmic membrane. Before the protein achieves its mature form, the Sec machinery recognizes the signal peptide and translocates the pre-protein across the cytoplasmic membrane, during which time the lipophilic region of the signal peptide becomes embedded in the cytoplasmic membrane. SPase then cleaves the signal peptide to release the protein. SPase also functions at the terminal step of the twin-arginine translocase (Tat) pathway. The Tat pathway is functionally similar to the Sec pathway, but it recognizes signal peptides containing a highly conserved R-R motif, and its pre-protein cargo fold prior to translocation across the cytoplasmic membrane. But SPase has also relevant biological functions outside of mediating secretion. SPase is required for virulence. SPase processes components of multimeric secretion systems. SPase plays an essential role in the assembly of multiple secretion systems through the processing of secretins, which are large, multimeric proteins that localize to the outer membrane
PDB
SCOP
CATH
UNIPROT
ORGANISM
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
13000
-
1 * 18000 + 1 * 20000 + 1 * 25000 + 1 * 13000 (the association of the 13000 MW protein with the enzymatic activity is tentative), yeast, SDS-PAGE
18000
-
1 * 18000 + 1 * 20000 + 1 * 25000 + 1 * 13000 (the association of the 13000 MW protein with the enzymatic activity is tentative), yeast, SDS-PAGE
20000
-
1 * 18000 + 1 * 20000 + 1 * 25000 + 1 * 13000 (the association of the 13000 MW protein with the enzymatic activity is tentative), yeast, SDS-PAGE
25000
-
1 * 18000 + 1 * 20000 + 1 * 25000 + 1 * 13000 (the association of the 13000 MW protein with the enzymatic activity is tentative), yeast, SDS-PAGE
27910
-
E. coli, detergent-free DELTA2-75 mutant protein lacking the two N-terminal transmembrane spanning and the cytoplasmic domains, calculation from amino acid sequence
27950
37000
27950
-
E. coli detergent-free DELTA2-75 mutant protein lacking the two N-terminal transmembrane spanning and the cytoplasmic domains, electrospray ionization mass spectrometry
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
monomer
?
-
1 * 18000 + 1 * 20000 + 1 * 25000 + 1 * 13000 (the association of the 13000 MW protein with the enzymatic activity is tentative), yeast, SDS-PAGE
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
soluble catalytic domain of SSPase I in ternary complex with inhibitors arylomycin A2 and BAL0019193, sitting drop vapor diffusion method at 18°C, mixing of 0.002 ml of protein solution and of reservoir solution, containing 0.2 M ammonium formate, 25% PEG 2000, 0.1 M sodium cacodylate pH 6.5, and 5% tertiary-amyl alcohol, equilibration over 1 ml reservoir solution, X-ray diffraction structure determination and analysis at 2.0 A resolution, molecular replacement
dynamic conformational changes of soluble, catalytically active variant DELTA2-75
mutant delta2-75 in complex with beta-lactam inhibitor (5S,6S) penem, crystals belong to orthorhombic space group P2(1)2(1)2 with unit cell dimensions a : 110.7 A, b : 113.2 A, c : 99.2 A, crystal structure of apoenzyme in absence of substrate or inhibitor solved by molecular replacement, space group P4(1)2(1)2, unit cell dimensions a : b : 112.4 A, c : 198.7 A
-
presence of Triton X-100 is required to obtain crystals sufficiently large for X-ray analysis
-
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
I144C
50% of wild-type activity, mutant enzyme cleaves at multiple sites
I86A/I144A
mutant enzyme is able to cleave after Phe at the -1 residue
R222A
-
kcat is about 5.5fold smaller than the wild-type value, Km-is almost identical to wild-type value. Thermostability is significantly lower compared to the wild-type enzyme
R222K
-
kcat is about 5.5fold smaller than the wild-type value, Km-is almost identical to wild-type value. Thermostability is significantly lower compared to the wild-type enzyme
R315A
-
kcat is about 5.5fold smaller than the wild-type value, Km-is almost identical to wild-type value. Thermostability is significantly lower compared to the wild-type enzyme
R318A
-
kcat is about 5.5fold smaller than the wild-type value, Km-is almost identical to wild-type value
R318K
-
kcat is about 5.5fold smaller than the wild-type value, Km-is almost identical to wild-type value. Thermostability is significantly lower compared to the wild-type enzyme
R77A
-
kcat is about 5.5fold smaller than the wild-type value, Km-is almost identical to wild-type value
R77K
-
kcat is about 5.5fold smaller than the wild-type value, Km-is almost identical to wild-type value
W261F/W284F/W300F
mutant based on deletion mutant DELTA2-75. Mutant contains one remaining Trp residue and is able to insert into lipids
W261F/W284F/W310F
mutant based on deletion mutant DELTA2-75. Mutant contains one remaining Trp residue and is able to insert into lipids
W261F/W300F/W310F
mutant based on deletion mutant DELTA2-75. Mutant contains one remaining Trp residue, its solvent accesibilities are modified in the presence of signal peptide
W284F/W300F/W310F
mutant based on deletion mutant DELTA2-75. Mutant contains one remaining Trp residue, its solvent accesibilities are modified in the presence of signal peptide
additional information
additional information
generation of a DELTA2-76 truncated enzyme mutant by deletion. The mutant is soluble and lacks both N-terminal transmembrane domains
additional information
-
generation of a DELTA2-76 truncated enzyme mutant by deletion. The mutant is soluble and lacks both N-terminal transmembrane domains
additional information
-
expression of a soluble form of signal peptidase, which lacks the two transmembrane domains, SPase I DELTA2-75
additional information
-
variant DELTA2-75 is a soluble form of signal peptidase, which lacks the two transmembrane domains
pH STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
40
40
-
after 40°c there is a marked decrease in the rate that is due to the denaturationof Spase I
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
Stable at low ionic strength in solutions of nonionic detergents at low temperature
-
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
-20°C, 10 mM sodium phosphate, 10% glycerol, 0.05% Emulphogen BC-720 (Sigma) and 1 mM beta-mercaptoethanol, pH 7.2, stable for more than 6 months
-
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
-
-
doubly 13C, 15N- and singly 15N-isotopically labeled C-terminal SPase I DELTA2-75
-
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
plasmid pMC-Spase encoding signal peptidase transformed and amplified in Escherichia coli TB1
doubly 13C, 15N- and singly 15N-isotopically labeled C-terminal SPase I DELTA2-75 expressed in Escherichia coli BL21(DE3) cells
-
expressed in Escherichia coli BL21 (DE3) cells transfected with the pET23b-coding SPase I plasmid
-
expression of a soluble form of signal peptidase, which lacks the two transmembrane domains, SPase I DELTA2-75
-
methods for the identification of the leader peptidase gene and genetic manipulations to determine the role of leader peptidase in cell growth
-
RENATURED/Commentary
ORGANISM
UNIPROT
LITERATURE
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
drug development
medicine
-
inhibition of enzyme by arylomycin A-C16 results in an insufficient flux of proteins through the secretion pathway leading to mislocalization of proteins. Inhibition results in synergistic sensitivity of cells when combined with an aminoglycoside. No significant interactions are observed between arylomycin A-C16 and erythromycin, polymyxin B, trimethoprim, or ciprofloxacin. Arylomycin A-C16 shows mild synergism with cephalexin, pronounced synergism with rifampin and gentamicin, and antagonism with the translational inhibitor tetracycline
pharmacology
drug development
SPase I is a target for development of inhibitors as antibiotics
drug development
bacterial signal peptidase I (SPase) is a target for development of beta-lactam anti-bacterial inhibitors
drug development
bacterial signal peptidase I (SPase) represents an attractive target in that SPase inhibitors exhibit broad-spectrum antibiotic activity, but even at sub-MIC doses also impair the secretion of essential virulence factors
pharmacology
-
enzyme is essential for bacterial cell viability, potential molecular target for development of novel antibacterial agents
pharmacology
-
signal peptidase structure will be useful in the design of new and improved inhibitors which may be of pharmaceutical importance
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Tschantz, W.R.; Dalbey, R.E.
Bacterial leader peptidase 1
Methods Enzymol.
244
285-301
1994
Escherichia coli, Escherichia coli MC1061/pRD8
Tschantz, W.R.; Sung, M.; Delgado-Partin, V.M.; Dalbey, R.E.
A serine and a lysine residue implicated in the catalytic mechanism of the Escherichia coli leader peptidase
J. Biol. Chem.
268
27349-27354
1993
Escherichia coli
Black, M.T.
Evidence that the catalytic activity of prokaryote leader peptidase depends upon the operation of a serine-lysine catalytic dyad
J. Bacteriol.
175
4957-4961
1993
Escherichia coli
Wolfe, P.B.; Zwizinski, C.; Wickner, W.
Purification and characterization of leader peptidase from Escherichia coli
Methods Enzymol.
97
40-46
1983
Escherichia coli
Date, T.; Silver, P.; Wickner, W.
Molecular genetics of Escherichia coli leader peptidase
Methods Enzymol.
97
46-57
1983
Escherichia coli
Dalbey, R.E.; von Heijne, G.
Signal peptidases in prokaryotes and eukaryotes--a new protease family [published erratum appears in Trends Biochem Sci 1993 Jan;18(1):25]
Trends Biochem. Sci.
17
474-478
1992
Saccharomyces cerevisiae, Gallus gallus, Escherichia coli, Pseudomonas fluorescens, Salmonella enterica subsp. enterica serovar Typhimurium
Muller, M.
Proteolysis in protein import and export: signal peptide processing in eu- and prokaryotes
Experientia
48
118-129
1992
Saccharomyces cerevisiae, Canis lupus familiaris, Gallus gallus, Escherichia coli, Neurospora crassa, Pisum sativum, Rattus norvegicus
Anderson, C.M.; Gray, J.
Cleavage of the precursor of pea chloroplast cytochrome f by leader peptidase from Escherichia coli
FEBS Lett.
280
383-386
1991
Escherichia coli
Barkocy-Gallagher, G.A.; Bassford, P.J.
Synthesis of precursor maltose-binding protein with proline in the +1 position of the cleavage site interferes with the activity of Escherichia coli signal peptidase I in vivo
J. Biol. Chem.
267
1231-1238
1992
Escherichia coli
Black, M.T.; Munn, J.G.R.; Allsop, A.E.
On the catalytic mechanism of prokaryotic leader peptidase 1
Biochem. J.
282
539-543
1992
Escherichia coli, Pseudomonas fluorescens
Kuo, D.W.; Chan, H.K.; Wilson, C.J.; Griffin, P.R.; Williams, H.; Knight, W.B.
Escherichia coli leader peptidase: production of an active form lacking a requirement for detergent and development of peptide substrates
Arch. Biochem. Biophys.
303
274-280
1993
Escherichia coli
Kuo, D.; Weidner, J.; Griffin, P.; Shah, S.K.; Knight, W.B.
Determination of the kinetic parameters of Escherichia coli leader peptidase activity using a continuous assay: the pH dependence and time-dependent inhibition by beta-lactams are consistent with a novel serine protease mechanism
Biochemistry
33
8347-8354
1994
Escherichia coli
Chatterjee, S.; Suciu, D.; Dalbey, R.E.; Kahn, P.C.; Inouye, M.
Determination of Km and kcat for signal peptidase I using a full length secretory precursor, pro-OmpA-nuclease A
J. Mol. Biol.
254
311-314
1995
Escherichia coli
Tschantz, W.R.; Paetzel, M.; Cao, G.; Suciu, D.; Inouye, M.; Dalbey, R.E.
Characterization of a soluble, catalytically active form of Escherichia coli leader peptidase: requirement of detergent or phospholipid for optimal activity
Biochemistry
34
3935-3941
1995
Escherichia coli
Kim, Y.T.; Muramatsu, T.; Takahashi, K.
Leader peptidase from Escherichia coli: overexpression, characterization, and inactivation by modification of tryptophan residues 300 and 310 with N-bromosuccinimide
J. Biochem.
117
535-544
1995
Escherichia coli
Paetzel, M.; Chernaia, M.; Strynadka, N.; Tschantz, W.; Cao, G.; Dalbey, R.E.; James, M.N.G.
Crystallization of a soluble, catalytically active form of Escherichia coli leader peptidase
Proteins Struct. Funct. Genet.
23
122-125
1995
Escherichia coli
Talarico, T.L.; Dev, I.K.; Bassford, P.J.; Ray, R.H.
Inter-molecular degradation of signal peptidase I in vitro
Biochem. Biophys. Res. Commun.
181
650-656
1991
Escherichia coli, Escherichia coli MC1061
Wickner, W.; Moore, K.; Dibb, N.; Geissert, D.; Rice, M.
Inhibition of purified Escherichia coli leader peptidase by the leader (signal) peptide of bacteriophage M13 procoat
J. Bacteriol.
169
3821-3822
1987
Escherichia coli
Halpin, C.; Elderfield, P.D.; James, H.E.; Zimmermann, R.; Dunbar, B.; Robinson, C.
The reaction specificities of the thylakoidal processing peptidase and Escherichia coli leader peptidase are identical
EMBO J.
82
3917-3921
1989
Escherichia coli
Dev, I.K.; Ray, P.H.; Novak, P.
Minimum substrate sequence for signal peptidase I of Escherichia coli
J. Biol. Chem.
265
20069-20072
1990
Escherichia coli
Zwizinski, C.; Wickner, W.
Purification and characterization of leader (signal) peptidase from Escherichia coli
J. Biol. Chem.
255
7973-7977
1980
Escherichia coli
Wolfe, P.B.; Silver, P.; Wickner, W.
The isolation of homogeneous leader peptidase from a strain of Escherichia coli which overproduces the enzyme
J. Biol. Chem.
257
7898-7902
1982
Escherichia coli, Escherichia coli overproducing
Dierstein, R.; Wickner, W.
Requirements for substrate recognition by bacterial leader peptidase
EMBO J.
5
427-431
1986
Escherichia coli
Dalbey, R.E.; Wickner, W.
Leader peptidase of Escherichia coli: critical role of a small domain in membrane assembly
Science
235
783-787
1987
Escherichia coli
Novak, P.; Dev, I.K.
Degradation of a signal peptide by protease IV and oligopeptidase A
J. Bacteriol.
170
5067-5075
1988
Escherichia coli
Geukens, N.; Frederix, F.; Reekmans, G.; Lammertyn, E.; Van Mellaert, L.; Dehaen, W.; Maes, G.; Anne, J.
Analysis of type I signal peptidase affinity and specificity for preprotein substrates
Biochem. Biophys. Res. Commun.
314
459-467
2004
Escherichia coli, Streptomyces lividans
Stein, R.L.; Barbosa, M.D.F.S.; Bruckner, R.
Kinetic and mechanistic studies of signal peptidase I from Escherichia coli
Biochemistry
39
7973-7983
2000
Escherichia coli
Gallagher, J.; Kaderbhai, N.N.; Kaderbhai, M.A.
Kinetic constants of signal peptidase I using cytochrome b5 as a precursor substrate
Biochim. Biophys. Acta
1550
1-5
2001
Escherichia coli
Bruton, G.; Huxley, A.; O'Hanlon, P.; Orlek, B.; Eggleston, D.; Humphries, J.; Readshaw, S.; West, A.; Ashman, S.; Brown, M.; Moore, K.; Pope, A.; O'Dwyer, K.; Wang, L.
Lipopeptide substrates for SpsB, the Staphylococcus aureus type I signal peptidase: design, conformation and conversion to alpha-ketoamide inhibitors
Eur. J. Med. Chem.
38
351-356
2003
Escherichia coli, Staphylococcus aureus
Ichihara, S.; Suzuki, T.; Suzuki, M.; Mizushima, S.
Molecular cloning and sequencing of the sppA gene and characterization of the encoded protease IV, a signal peptide peptidase, of Escherichia coli
J. Biol. Chem.
261
9405-9411
1986
Escherichia coli
Carlos, J.L.; Paetzel, M.; Brubaker, G.; Karla, A.; Ashwell, C.M.; Lively, M.O.; Cao, G.; Bullinger, P.; Dalbey, R.E.
The role of the membrane-spanning domain of type I signal peptidases in substrate cleavage site selection
J. Biol. Chem.
275
38813-38822
2000
Escherichia coli (P00803), Escherichia coli, Bacillus subtilis (P28628), Bacillus subtilis
Klenotic, P.A; Carlos, J.L.; Samuelson, J.C.; Schuenemann, T.A.; Tschantz, W.R.; Paetzel, M.; Strynadka, N.C.J.; Dalbey, R.E.
The role of the conserved box E residues in the active site of the Escherichia coli type I signal peptidase
J. Biol. Chem.
275
6490-6498
2000
Escherichia coli
Paetzel, M.; Dalbey, R.E.; Strynadka, N.C.J.
Crystal structures of a bacterial signal peptidase in complex with a beta-lactam inhibitor
Nature
396
186-190
1998
Escherichia coli
Suciu, D.; Chatterjee, S.; Inouye, M.
Catalytic efficiency of signal peptidase I of Escherichia coli is comparable to that of members of the serine protease family
Protein Eng.
10
1057-1060
1997
Escherichia coli
Dalbey, R.E.; Lively, M.O.; Bron,S.; Van Diijl, J.M.
The chemistry and enzymology of the type I signal peptidases
Protein Sci.
6
1129-1138
1997
Bacillus amyloliquefaciens, [Bacillus] caldolyticus, Bacillus subtilis, Bacillus licheniformis, Bradyrhizobium japonicum, Saccharomyces cerevisiae, Canis lupus familiaris, Gallus gallus, Escherichia coli, Haemophilus influenzae, Methanocaldococcus jannaschii, Staphylococcus aureus, Mycobacterium tuberculosis, no activity in Mycoplasma genitalium, Phormidium laminosum, Pseudomonas fluorescens, Rana sp., Rattus norvegicus, Salmonella enterica subsp. enterica serovar Typhimurium, Caenorhabditis elegans (P34525), Schizosaccharomyces pombe (Q10259), Homo sapiens (Q15005), Rhodobacter capsulatus (Q52697)
Paetzel, M.; Strynadka, N.C.J.
Common protein architecture and binding sites in proteases utilizing a Ser/Lys dyad mechanism
Protein Sci.
8
2533-2536
1999
Escherichia coli
Wang, Y.; Bruckner, R.; Stein, R.L.
Regulation of signal peptidase by phospholipids in membrane: characterization of phospholipid bilayer-incorporated Escherichia coli signal peptidase
Biochemistry
43
265-270
2004
Escherichia coli
Kim, Y.T.; Kurita, R.; Kojima, M.; Nishii, W.; Tanokura, M.; Muramatsu, T.; Ito, H.; Takahashi, K.
Identification of arginine residues important for the activity of Escherichia coli signal peptidase I
Biol. Chem.
385
381-388
2004
Escherichia coli
Kulanthaivel, P.; Kreuzman, A.J.; Strege, M.A.; Belvo, M.D.; Smitka, T.A.; Clemens, M.; Swartling, J.R.; Minton, K.L.; Zheng, F.; Angleton, E.L.; Mullen, D.; Jungheim, L.N.; Klimkowski, V.J.; Nicas, T.I.; Thompson, R.C.; Peng, S.B.
Novel lipoglycopeptides as inhibitors of bacterial signal peptidase I
J. Biol. Chem.
279
36250-36258
2004
Streptococcus pneumoniae, Escherichia coli
Karla, A.; Lively, M.O.; Paetzel, M.; Dalbey, R.
The identification of residues that control signal peptidase cleavage fidelity and substrate specificity
J. Biol. Chem.
280
6731-6741
2005
Escherichia coli (P00803)
Musial-Siwek, M.; Kendall, D.A.; Yeagle, P.L.
Solution NMR of signal peptidase, a membrane protein
Biochim. Biophys. Acta
1778
937-944
2008
Escherichia coli
Musial-Siwek, M.; Yeagle, P.L.; Kendall, D.A.
A small subset of signal peptidase residues are perturbed by signal peptide binding
Chem. Biol. Drug Des.
72
140-146
2008
Escherichia coli
Kaderbhai, N.N.; Harding, V.; Kaderbhai, M.A.
Signal peptidase I-mediated processing of an engineered mammalian cytochrome b(5) precursor is an exocytoplasmic post-translocational event in Escherichia coli
Mol. Membr. Biol.
25
388-399
2008
Escherichia coli (P00803), Escherichia coli
Luo, C.; Roussel, P.; Dreier, J.; Page, M.G.; Paetzel, M.
Crystallographic analysis of bacterial signal peptidase in ternary complex with arylomycin A2 and a beta-sultam inhibitor
Biochemistry
48
8976-8984
2009
Escherichia coli (P00803), Escherichia coli
De Bona, P.; Deshmukh, L.; Gorbatyuk, V.; Vinogradova, O.; Kendall, D.A.
Structural studies of a signal peptide in complex with signal peptidase I cytoplasmic domain: The stabilizing effect of membrane-mimetics on the acquired fold
Proteins
80
807-817
2011
Escherichia coli
Smith, P.A.; Romesberg, F.E.
Mechanism of action of the arylomycin antibiotics and effects of signal peptidase I inhibition
Antimicrob. Agents Chemother.
56
5054-5060
2012
Escherichia coli, Staphylococcus aureus
Bhanu, M.; Kendall, D.
Fluorescence spectroscopy of soluble E. coli SPase I DELTA2-75 reveals conformational changes in response to ligand binding
Proteins
82
596-606
2014
Escherichia coli (A0A140N8W1), Escherichia coli
Yeh, C.H.; Walsh, S.I.; Craney, A.; Tabor, M.G.; Voica, A.F.; Adhikary, R.; Morris, S.E.; Romesberg, F.E.
Optimization of a beta-lactam scaffold for antibacterial activity via the inhibition of bacterial type I signal peptidase
ACS Med. Chem. Lett.
9
376-380
2018
Yersinia pestis, Staphylococcus epidermidis, Escherichia coli (P00803), Escherichia coli MG1655 (P00803), Staphylococcus epidermidis RP26A, Yersinia pestis KIM+6
Zalucki, Y.M.; Jennings, M.P.
Signal peptidase I processed secretory signal sequences selection for and against specific amino acids at the second position of mature protein
Biochem. Biophys. Res. Commun.
483
972-977
2017
Methanococcus voltae, Sulfurisphaera tokodaii, Escherichia coli (P00803), Saccharomyces cerevisiae (P15367), Saccharomyces cerevisiae, Bacillus subtilis (P28628), Bacillus subtilis 168 (P28628), Sulfurisphaera tokodaii 7, Methanococcus voltae A3, Saccharomyces cerevisiae ATCC 204508 (P15367)
Musik, J.E.; Zalucki, Y.M.; Day, C.J.; Jennings, M.P.
Efficient function of signal peptidase 1 of Escherichia coli is partly determined by residues in the mature N-terminus of exported proteins
Biochim. Biophys. Acta
1861
1018-1022
2019
Escherichia coli (P00803), Escherichia coli
Walsh, S.I.; Craney, A.; Romesberg, F.E.
Not just an antibiotic target exploring the role of type I signal peptidase in bacterial virulence
Bioorg. Med. Chem.
24
6370-6378
2016
Actinomyces sp., Corynebacterium diphtheriae, Streptococcus pneumoniae, Listeria monocytogenes, Streptococcus agalactiae, Enterococcus sp., Streptococcus gallolyticus, Clostridioides difficile (A0A031W9H6), Lacticaseibacillus rhamnosus (A0A180C927), Enterococcus faecalis (A0A1B4XP47), Bacillus anthracis (A0A1S0QR24), Streptococcus pyogenes (A0A4U7IU30), Bacillus cereus (A0A7D3YGV4), Escherichia coli (P00803), Staphylococcus aureus (P0A070), Staphylococcus epidermidis (Q5HQJ6), Pseudomonas aeruginosa (Q9I5G7), Pseudomonas aeruginosa ATCC 15692 (Q9I5G7), Pseudomonas aeruginosa 1C (Q9I5G7), Staphylococcus epidermidis ATCC 35984 (Q5HQJ6), Pseudomonas aeruginosa PRS 101 (Q9I5G7), Bacillus cereus 03BB108 (A0A7D3YGV4), Pseudomonas aeruginosa DSM 22644 (Q9I5G7), Pseudomonas aeruginosa CIP 104116 (Q9I5G7), Pseudomonas aeruginosa LMG 12228 (Q9I5G7), Pseudomonas aeruginosa JCM 14847 (Q9I5G7)
EXTERNAL LINKS (specific for EC-Number 3.4.21.89)
Transporter Classification Database (TCDB): 9.B.391.1.3
Use of this online version of BRENDA is free under the CC BY 4.0 license. See terms of use for full details.
Release 2023.1 (January 2023)
Legal
Curated at
Member of
