3.4.21.89: Signal peptidase I
This is an abbreviated version!
For detailed information about Signal peptidase I, go to the full flat file.
Word Map on EC 3.4.21.89
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3.4.21.89
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polyproteins
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lipoprotein
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preproteins
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cleavable
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foot-and-mouth
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unprocessed
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dyad
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membrane-spanning
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prolipoproteins
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translocons
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pilins
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uncleaved
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beta-lactamase
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drug development
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flavivirus
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ompa
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nonstructural
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cotranslationally
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co-translational
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sec-dependent
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globomycin
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presequence
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papain-like
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prepeptide
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polytopic
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oligonucleotide-directed
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ns2b
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signal-anchored
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pharmacology
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medicine
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analysis
- 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
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nonstructural
-
cotranslationally
-
co-translational
-
sec-dependent
- globomycin
- presequence
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papain-like
- prepeptide
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polytopic
-
oligonucleotide-directed
- ns2b
-
signal-anchored
- pharmacology
- medicine
- analysis
Reaction
Cleavage of hydrophobic, N-terminal signal or leader sequences =
Synonyms
Bacterial leader peptidase 1, bacterial type I signal peptidase, big signal peptidase, canine signal peptidase complex, chloroplast processing peptidase, EC 3.4.99.36, Escherichia coli leader peptidase, Eukaryotic signal peptidase, Eukaryotic signal proteinase, hen oviduct signal peptidase, HOSP, imp1p, Leader peptidase, Leader peptidase I, Leader peptide hydrolase, Leader proteinase, LEP, LepB, PA1303, Pcp1, Peptidase, signal, Pilin leader peptidase, plastidic SPase I, plastidic SPase I 1, plastidic type I signal peptidase 1, Plsp1, Prokaryotic leader peptidase, Prokaryotic signal peptidase, Prokaryotic signal proteinase, Propeptidase, protease IV, Proteinase, eukaryotic signal, Proteinase, signal, PuIO prepilin peptidase, Rv2903c, SEC11, secretory protein 11, Signal peptidase, signal peptidase I, signal peptidase I-3, Signal peptidase IB, signal peptidase type I, Signal peptide hydrolase, Signal peptide peptidase, Signalase, Sip1, Sip2, Sip3, SipP (pTA1015), SipP (pTA1040), SipS, SipT, SipU, SipV, SipW, SipX, SipY, SipZ, SP, SP I, SP-I, SPase, Spase I, SPase I 1, SPase IB, SPaseI, SPC, Spc1, SPI, SPP, SpsB, thylakoidal processing peptidase, TPP, type I signal (leader) peptidase, type I signal peptidase, type I signal peptidase 1, type I signal peptidase Sec11a, type I signal peptidase Sec11b, type I SPase
ECTree
3.4.21.89 Signal peptidase IAdvanced search results
results (
results (Inhibitors
Inhibitors on EC 3.4.21.89 - Signal peptidase I
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INHIBITOR 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
IMAGE
(3S)-3-((1R)-1-[(N-decanoyl-L-prolyl-L-threonyl-L-alanyl-L-asparaginyl)amino]ethyl)azetidin-2-one
-
beta-lactam lipopeptide, 57% inhibition at 0.1 mM
(3S)-3-((1S)-1-[(N-decanoyl-L-prolyl-L-threonyl-L-alanyl-L-asparaginyl)amino]ethyl)azetidin-2-one
-
beta-lactam lipopeptide, 47% inhibition at 0.1 mM
(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
(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
(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
(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
(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
(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
(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
(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
(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
(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
(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
(5S,6S)-6-[(2R)-2-hydroxypropyl]-7-oxo-4-thia-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid
(Z-LL)2-ketone
-
completely abolishes signal peptide peptidase-catalysed maturation of p23 to p21 in the case of wild-type
1-(2,5-dichlorophenyl)-3-(dimethylamino)propan-1-one
overexpression of lepB reduces the susceptibility of Mycobacterium tuberculosis to 1-(2,5-dichlorophenyl)-3-(dimethylamino)propan-1-one, and downregulation results in increased susceptibility. Treatment with 1-(2,5-dichlorophenyl)-3-(dimethylamino)propan-1-one leads to a rapid loss of viability and cell lysis. The compound has increased potency in nonreplicating cells, causing a reduction in viable cell numbers below the detection limit after 24 h
4-nitrobenzyl (5S,6S)-6-(1-hydroxyethyl)-7-oxo-4-thia-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate
-
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4-nitrobenzyl (5S,6S)-6-[(1R)-1-(acetyloxy)ethyl]-7-oxo-4-thia-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate
-
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4-nitrobenzyl (5S,6S)-6-[(1R)-1-(butanoyloxy)ethyl]-7-oxo-4-thia-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate
-
-
4-nitrobenzyl (5S,6S)-6-[(1R)-1-(ethoxymethoxy)ethyl]-7-oxo-4-thia-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate
-
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4-nitrobenzyl (5S,6S)-6-[(1R)-1-(methoxymethoxy)ethyl]-7-oxo-4-thia-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate
-
-
4-nitrobenzyl (5S,6S)-6-[(1R)-1-[(2-methylbutanoyl)oxy]ethyl]-7-oxo-4-thia-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate
-
-
4-nitrobenzyl (5S,6S)-6-[(1R)-1-[(2-methylpropanoyl)oxy]ethyl]-7-oxo-4-thia-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate
-
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4-nitrobenzyl (5S,6S)-6-[(1R)-1-[(acetyloxy)methoxy]ethyl]-7-oxo-4-thia-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate
-
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4-nitrobenzyl (5S,6S)-6-[(1R)-1-[(ethylcarbamoyl)oxy]ethyl]-7-oxo-4-thia-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate
-
-
4-nitrobenzyl (5S,6S)-6-[(1R)-1-[(N-acetylalanyl)oxy]ethyl]-7-oxo-4-thia-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate
-
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4-nitrobenzyl (5S,6S)-6-[(1R)-1-[(N-acetylglycyl)oxy]ethyl]-7-oxo-4-thia-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate
-
-
4-nitrobenzyl (5S,6S)-6-[(1R)-1-[(N-acetylisoleucyl)oxy]ethyl]-7-oxo-4-thia-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate
-
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4-nitrobenzyl (5S,6S)-6-[(1R)-1-[(N-acetylvalyl)oxy]ethyl]-7-oxo-4-thia-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate
-
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4-nitrobenzyl (5S,6S)-7-oxo-6-[(1R)-1-(propanoyloxy)ethyl]-4-thia-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate
-
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4-nitrobenzyl (5S,6S)-7-oxo-6-[(1R)-1-[(propan-2-ylcarbamoyl)oxy]ethyl]-4-thia-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate
-
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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
benzyl (2S,5R,6S)-6-[(N-decanoyl-L-prolyl-L-threonyl-L-alanyl-L-asparaginyl)amino]-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]-heptane-2-carboxylate
-
beta-lactam lipopeptide, 36% inhibition at 0.1 mM
Bromosuccinimide
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inactivation by modification of tryptophan residues 300 and 310
Ciprofloxacin
-
1-cyclopropyl-6-fluoro-4-oxo-7-piperazin-1-ylquinoline-3-carboxylic acid
decanoyl-L-prolyl-L-threonyl-L-alanyl-L-asparaginyl-carboxamide
-
beta-lactam lipopeptide, 60% inhibition at 100 mM, removal of the beta-lactam moiety results in a loss of activity
decanoyl-LTPTA
-
susceptible to classic protease inhibition, SpsB can be inhibited with a P1' proline
L685,458
-
exerts only a slight effect on signal peptide peptidase-catalysed maturation of p23 to p21 in the case of wild-type, but it almost completely abolishes this process in the case of the Con1/C3/VLV replicon
lactacystin
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proteasome inhibitor, presence in cells infected with mouse mammary tumor virus results in accumulation of uncleaved Rem relative to SP, consistent with SP retrotranslocation and proteasome escape before nuclear entry
Leader peptide of bacteriophage procoat
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inhibits cleavage of M13 procoat or pre-maltose-binding protein
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MG132
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proteasome inhibitor, presence in cells infected with mouse mammary tumor virus results in accumulation of uncleaved Rem relative to SP, consistent with SP retrotranslocation and proteasome escape before nuclear entry
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
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
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
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
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
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
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
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
N-[(1S)-1-(chloroacetyl)-3-methylbutyl]-4-methylbenzenesulfonamide
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total loss of enzyme activity
N-[(2S)-4-[(2S)-1-decanoylpyrrolidin-2-yl]-2-(1-hydroxyethyl)-4-oxobutanoyl]-L-alanyl-N1-[(2S)-1-oxopropan-2-yl]-L-aspartamide
-
i.e. decanoyl-PTANA-aldehyde, inhibition by the synthetic substrate-based peptide aldehyde, overview. The length of the core lipopeptide can be reduced by removing several amino acids from both termini. Conversion of this peptide to an aldehyde. The signal peptide consists of three domains, a positively charged N-terminal domain, n-region, a hydrophobic middle domain, which contains usually 7-15 amino acids forming an alpha-helix, h-region, and a C-terminal domain, c-region, which is responsible for substrate recognition
pre-protein including a proline at the +1 position
-
not cleaved, act as competitive inhibitors
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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
(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-aminoethyl)sulfanyl]-6-[(1R)-1-hydroxyethyl]-7-oxo-4-thia-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid
-
-
(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
-
-
(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-(carbamoyloxy)ethyl]sulfanyl]-6-[(1R)-1-hydroxyethyl]-7-oxo-4-thia-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid
-
-
(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
-
-
(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-[[2-(dimethylamino)ethyl]sulfanyl]-6-[(1R)-1-hydroxyethyl]-7-oxo-4-thia-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid
-
-
(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
-
-
(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)-3-[[3-(dimethylcarbamoyl)cyclopentyl]sulfanyl]-6-[(1R)-1-hydroxyethyl]-7-oxo-4-thia-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid
-
-
(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
-
-
(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-[(iminomethyl)amino]ethyl]sulfanyl)-7-oxo-4-thia-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid
-
-
(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
-
-
(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-hydroxyethyl)sulfanyl]-7-oxo-4-thia-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid
-
-
(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
-
-
(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]-3-[[2-(methylamino)ethyl]sulfanyl]-7-oxo-4-thia-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid
-
-
(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
-
-
(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-[[(1R)-3-oxocyclopentyl]sulfanyl]-4-thia-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid
-
-
(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
-
-
(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-[[(3R)-pyrrolidin-3-yl]sulfanyl]-4-thia-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid
-
-
(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
-
-
(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-[[(3S)-pyrrolidin-3-yl]sulfanyl]-4-thia-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid
-
-
(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
-
-
(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-[(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
-
-
(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
-
-
(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
(5S,6S)-6-[(2R)-2-hydroxypropyl]-7-oxo-4-thia-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid
-
-
(5S,6S)-6-[(2R)-2-hydroxypropyl]-7-oxo-4-thia-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid
-
-
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
A0A1S0QR24
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
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
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
-
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
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
-
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
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
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
-
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
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
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. The presence of Staphylococcus aureus proteins in the media fraction is inversely correlated with the arylomycin dose. Among the SPase secretome are many known virulence factors such as membrane damaging toxins, cell wall attached proteins for immune evasion, proteases that cleave host factors, and coagulases that promote prothrombin activation and may lead to protection from phagocytosis
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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. The presence of Staphylococcus epidermidis proteins in the media fraction is inversely correlated with the arylomycin dose. Among the SPase secretome are many known virulence factors such as membrane damaging toxins, cell wall attached proteins for immune evasion, proteases that cleave host factors, and coagulases that promote prothrombin activation and may lead to protection from phagocytosis
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arylomycin
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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
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arylomycin
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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
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arylomycin
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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
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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
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arylomycin A-C16
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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
arylomycin A-C16
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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
arylomycin A-C16
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secretion of proteins HtrA, PrsA, and SAOUHSC_01761 is induced by inhibitor treatment
arylomycin A-C16
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Yersinia pestis strain KIM6+, unlike most Enterobacteriaceae, is susceptible to the arylomycins, a class of natural-product lipopeptide antibiotics that inhibit signal peptidase I (SPase). The arylomycin activity is conserved against a broad range of Yersinia pestis strains, overview. Alterations to each component of the Yersinia pestis lipopolysaccharide (O antigen, core, and lipid A) make at most only a small contribution to the unique sensitivity against arylomycin, also an increased affinity of the Yersinia pestis SPase for the antibiotic is not detected. Instead, the origins of the sensitivity can be traced to an increased dependence on SPase activity that results from high levels of protein secretion under physiological conditions. Deletion of the gene encoding the highly expressed cell adhesion protein Ail (locus tag y1324, UniProt ID Q8D0Z7) significantly alleviates sensitivity and overexpression of Ail or Escherichia coli maltose-binding protein then restores sensitivity, the arylomycin susceptibility of Yersinia pestis results from a temperature-dependent increase in protein secretion
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
arylomycin A2
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a lipohexapeptide SPase I inhibitor, complete inhibition of each of the isozymes at 0.0002 mM by 0.00625 mM inhibitor
dithiothreitol
90% inhibition. Enzyme contains a redox-active Cys pair and requires disulfide bond formation between them for its activity in vitro
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
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IC50: 190 nM
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
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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
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IC50: 110 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
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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
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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
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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
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IC50: 130 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
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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
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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
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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
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IC50: 170 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
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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
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IC50: 130 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
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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
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IC50: 110 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
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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
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
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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
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additional information
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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
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additional information
A0A1S0QR24
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
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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
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additional information
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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-ethylmaleimide, L-trans-epoxysuccinyl-leucylamido (4-guanidino) butane, 1,2-epoxy-3-(p nitrophenoxy)propane, pepstatin, and diaxoacetyl-DL-norleucine methyl ester
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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
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additional information
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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
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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
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additional information
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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
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additional information
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but site-directed mutagenesis implicates a Ser/Lys catalytic dyad in activity; unaffected by inhibitors of most serine peptidases
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additional information
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but site-directed mutagenesis implicates a Ser/Lys catalytic dyad in activity
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additional information
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but site-directed mutagenesis implicates a Ser/Lys catalytic dyad in activity
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additional information
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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
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additional information
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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
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additional information
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scarcely inhibited by treatment with: N-acetylimidazole, iodoacetic acid, 5,5'-dithiobis(2-nitrobenzoic acid), succinic anhydride, 2,4,6-trinitrobenzenesulfonate
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additional information
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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
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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
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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
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
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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
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additional information
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not inhibited by thiol-, carboxyl-, or metalloproteinase inhibitors
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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
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additional information
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a substrate based peptide aldehyde inhibits signal peptidases with a lower IC(50) value than other lipopeptides
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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
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additional information
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inhibition by a synthetic substrate-based peptide aldehyde with IC50 of 0.009 mM and 0.013 mM for Sip2 and Sip3, respectively
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additional information
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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, MIC values against Staphylococcus epidermidis, overview
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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
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additional information
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synthesis of a 5S penem from 6-aminopenicillanic acid, structure-activity relationships, overview
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additional information
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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
-
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
-
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
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
-
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, MIC values against Yersinia pestis, overview
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additional information
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strain identifiers and MIC values of arylomycin A-C16 and ciprofloxacin for the 30-member Yersinia pestis panel, overview. The MIC values increase with decreasing temperature
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