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Information on EC 2.3.2.5 - glutaminyl-peptide cyclotransferase and Organism(s) Homo sapiens and UniProt Accession Q9NXS2
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2.3.2.5 glutaminyl-peptide cyclotransferaseIUBMB Comments
Involved in the formation of thyrotropin-releasing hormone and other biologically active peptides containing N-terminal pyroglutamyl residues. The enzyme from papaya also acts on glutaminyl-tRNA.
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Word Map
- 2.3.2.5
- pyroglutamate
- alzheimer
- cyclases
-
pyroglutamyl
- papaya
-
pyroglutamate-modified
-
pglu-a
- medicine
- drug development
-
antivenomics
- pharmacology
-
n-truncated
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cd47-sirp
The taxonomic range for the selected organisms is: Homo sapiens
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria, Archaea
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria, Archaea
Synonyms
glutaminyl cyclase, isoqc, qpctl, glutaminyl-peptide cyclotransferase, isodromeqc, glutamine cyclotransferase, dromeqc, golgi resident enzyme, golgi-resident enzyme, h-isoqc, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
cyclotransferase, glutaminyl-transfer ribonucleate
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glutaminyl cyclase
glutaminyl-tRNA cyclotransferase
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-
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QC
-
-
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sQC
glutaminyl cyclase
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-
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glutaminyl cyclase
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glutaminyl cyclase
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REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
L-glutaminyl-peptide = 5-oxoprolyl-peptide + NH3
DFT theoretical investigation on the catalytic mechanism of glutaminyl cyclase
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
aminoacyl group transfer
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PATHWAY SOURCE
PATHWAYS
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SYSTEMATIC NAME
IUBMB Comments
L-glutaminyl-peptide gamma-glutamyltransferase (cyclizing)
Involved in the formation of thyrotropin-releasing hormone and other biologically active peptides containing N-terminal pyroglutamyl residues. The enzyme from papaya also acts on glutaminyl-tRNA.
CAS REGISTRY NUMBER
COMMENTARY
37257-21-9
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SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
L-glutaminyl-monocyte chemoattractant protein 1
5-oxoprolyl-monocyte chemoattractant protein 1 + NH3
i.e. MCP-1 or CCL2
-
-
?
Gln-7-amido-4-methylcoumarin
L-pyroglutamyl-4-methylcoumarin-7-amide + NH3
-
-
-
-
?
Gln-7-amido-4-methylcoumarin
pyroglutamic acid-7-amido-4-methylcoumarin + NH3
-
-
-
?
Gln-Ala-Ala-Ser-Ala-Ala-NH2
pyroglutamic acid-Ala-Ala-Ser-Ala-Ala-NH2 + NH3
-
-
-
-
?
Gln-tert-butyl ester
pyroglutamyl-tert-butyl ester + NH3
-
-
-
-
?
H-Gln-7-amido-4-methylcoumarin
5-oxoprolyl-7-amido-4-methylcoumarin + NH3
-
-
-
-
?
L-Gln(3)-amyloid-beta peptide 3-42
L-pyroglutamyl(3)-amyloid-beta peptide 3-42 + NH3
-
-
-
-
?
L-Gln-2-naphthylamide
L-pyroglutamyl-2-naphthylamide + NH3
-
reaction in cell supernatant is exclusively enzyme-catalyzed
-
-
?
L-Gln-7-amido-4-methylcoumarin
5-oxoprolyl-7-amido-4-methylcoumarin + NH3
-
-
-
?
L-Gln-7-amido-4-methylcoumarin
pyroglutamate-7-amido-4-methylcoumarin + NH3
-
-
-
-
?
L-Gln-L-Glu-L-Asp-L-Leu-NH2
5-oxoprolyl-L-Glu-L-Asp-L-Leu-NH2 + NH3
-
-
-
?
L-Gln-L-Lys-L-Arg-L-Leu-NH2
5-oxoprolyl-L-Lys-L-Arg-L-Leu-NH2 + NH3
-
-
-
?
L-Glu(3)-amyloid-beta peptide 3-42
L-pyroglutamyl(3)-amyloid-beta peptide 3-42 + H2O
-
-
-
-
?
L-glutaminyl-4-methylcoumarinylamide
L-5-oxoprolyl-4-methylcoumarinylamide + NH3
-
-
-
-
?
L-glutaminyl-7-amido-4-methylcoumarin
L-pyroglutamyl-7-amido-4-methylcoumarin + NH3
-
-
-
?
L-glutaminyl-Abeta3-40/42
5-oxoprolyl-Abeta3-40/42 + NH3
amyloid-beta peptide Abeta3-40/42
-
-
r
L-glutaminyl-Abeta3-40/42 peptide
5-oxoprolyl-Abeta3-40/42 peptide + NH3
amyloid-beta peptide Abeta3-40/42
-
-
?
L-glutaminyl-amyloid beta peptide
5-oxoprolyl-amyloid beta peptide + NH3
-
-
-
-
?
L-glutaminyl-monocyte chemoattractant protein 1
5-oxoprolyl-monocyte chemoattractant protein 1 + NH3
i.e. MCP-1 or CCL2
-
-
?
L-glutaminyl-monocyte chemoattractant protein 3
5-oxoprolyl-monocyte chemoattractant protein 3 + NH3
i.e. MCP-3 or CCL7
-
-
?
[Gln1]-fertilization promoting peptide
[pyroglutamyl]-fertilization promoting peptide + NH3
-
-
-
-
?
[Gln1]-gonadotropin releasing-hormone
[pyroglutamyl]-gonadotropin releasing-hormone + NH3
-
-
-
-
?
[Gln1]-thyrotropin releasing-hormone
[pyroglutamyl]-thyrotropin releasing-hormone + NH3
-
-
-
-
?
L-glutaminyl-CCL2
5-oxoprolyl-CCL2 + NH3
i.e. monocyte chemoattractant protein (MCP-1)
-
-
r
L-glutaminyl-CCL2
5-oxoprolyl-CCL2 + NH3
i.e. monocyte chemoattractant protein (MCP-1), CCL2 is a specific substrate for h-isoQC but not for h-QC
-
-
r
L-glutaminyl-7-amido-4-methylcoumarin
pGlu-7-amido-4-methylcoumarin + NH3
-
-
-
-
?
L-glutaminyl-7-amido-4-methylcoumarin
pGlu-7-amido-4-methylcoumarin + NH3
-
-
-
?
L-glutaminyl-peptide
5-oxoprolyl-peptide + NH3
-
thyrotropin-releasing hormone
-
?
L-glutaminyl-peptide
5-oxoprolyl-peptide + NH3
-
the N-terminal formation of 5-oxoproline is a common post-translational event during biosynthesis of a number of peptides
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?
L-glutaminyl-peptide
5-oxoprolyl-peptide + NH3
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involved in posttranslational modification of the N-terminal glutamine of peptide hormones or neurotransmitters, such as thyrotropin releasing hormone, luteinizing hormone releasing hormone, gastrin, heavy chain of gamma-globulin
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-
?
additional information
?
-
cyclization reaction of glutamate and glutamine residues, overview
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additional information
?
-
cyclization reaction of glutamate and glutamine residues, overview
-
-
-
additional information
?
-
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the enzyme may play a key role in posttranslational modification
-
-
?
additional information
?
-
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enzyme is important during cellular maturation of L-pyroglutamyl-containing peptides
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-
?
additional information
?
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catalyzes the formation of amyloid-beta3(pE)-40/42 after amyloidogenic processing of amyloid precursor protein
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?
additional information
?
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orexin A, gastrin, gonadotropin, TRH, MCP-1 to 4, FPP, fibronectin, and neurotensin are substrates of the enzyme
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additional information
?
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cyclization reaction of glutamate and glutamine residues, overview. CCL2 is a specific substrate for h-isoQC but not for h-QC
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-
-
additional information
?
-
cyclization reaction of glutamate and glutamine residues, overview. CCL2 is a specific substrate for h-isoQC but not for h-QC
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-
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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
L-glutaminyl-CCL2
5-oxoprolyl-CCL2 + NH3
i.e. monocyte chemoattractant protein (MCP-1)
-
-
r
L-glutaminyl-Abeta3-40/42
5-oxoprolyl-Abeta3-40/42 + NH3
amyloid-beta peptide Abeta3-40/42
-
-
r
L-glutaminyl-Abeta3-40/42 peptide
5-oxoprolyl-Abeta3-40/42 peptide + NH3
amyloid-beta peptide Abeta3-40/42
-
-
?
L-glutaminyl-peptide
5-oxoprolyl-peptide + NH3
-
the N-terminal formation of 5-oxoproline is a common post-translational event during biosynthesis of a number of peptides
-
-
?
L-glutaminyl-peptide
5-oxoprolyl-peptide + NH3
-
involved in posttranslational modification of the N-terminal glutamine of peptide hormones or neurotransmitters, such as thyrotropin releasing hormone, luteinizing hormone releasing hormone, gastrin, heavy chain of gamma-globulin
-
-
?
additional information
?
-
-
the enzyme may play a key role in posttranslational modification
-
-
?
additional information
?
-
-
enzyme is important during cellular maturation of L-pyroglutamyl-containing peptides
-
-
?
additional information
?
-
orexin A, gastrin, gonadotropin, TRH, MCP-1 to 4, FPP, fibronectin, and neurotensin are substrates of the enzyme
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METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Zn2+
Co2+
enzyme inactivated by 1,10-phenanthroline or dipicolinic acid can be restored partially by Co2+ or Mn2+
Mn2+
enzyme inactivated by 1,10-phenanthroline or dipicolinic acid can be restored partially by Co2+ or Mn2+
Zn2+
additional information
Zn2+
enzyme inactivated by 1,10-phenanthroline or dipicolinic acid can be fully restored by addition of Zn2+ in the presence of equimolar concentrations of EDTA
Zn2+
the active site is coordinated to three conserved residues and one water molecule, which is replaced by an imidazole nitrogen upon binding of inhibitor
Zn2+
involved in catalysis, the Zn2+ ion located at the active site of QC polarizes the gamma-amide group of the substrate Gln residue and stabilizes the oxyanion formed by the nucleophilic attack of the alpha-nitrogen on the scissile gamma-carbonyl carbon
additional information
human glutaminyl cyclase and bacterial zinc aminopeptidase share a common fold and active site. Glutaminyl cyclase does not appear to require zinc for enzymatic activity
additional information
-
human glutaminyl cyclase and bacterial zinc aminopeptidase share a common fold and active site. Glutaminyl cyclase does not appear to require zinc for enzymatic activity
additional information
-
substrate specificity for substrates with uncharged backbone does not change significantly by salt addition. For substrates such as Gln-Ala and Gln-Glu, addition of KCl decreases specificity. With the positively charged substrates Gln-Arg-Gly-Ile-NH2 and Gln-Lys-Arg-Leu-NH2 addition of salt reveals a positive effect on catalysis
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
(E)-N1-(5-methyl-1H-imidazol-1-yl)-2-nitro-N'1-[4-(trifluoromethyl)phenyl]ethene-1,1-diamine
-
1,2-di-O-palmitoyl-3-O-(6'-deoxy-6'-sulfo-D-glycopyranosyl)-glycerol
-
1-(3,4-dimethoxyphenyl)-N-(1H-imidazol-1-yl)cyclopropane-1-carbothioamide
-
1-(3,4-dimethoxyphenyl)-N-(4-methyl-1H-imidazol-1-yl)cyclopropane-1-carbothioamide
-
1-(3,4-dimethoxyphenyl)-N-(5-methyl-1H-imidazol-1-yl)cyclopropane-1-carbothioamide
-
1-(3,4-dimethoxyphenyl)-N-[3-(1H-imidazol-1-yl)propyl]cyclopropane-1-carbothioamide
-
1-O-linolyl-2-O-palmitoyl-3-O-(6'-deoxy-6'-sulfo-D-glucopyranosyl)-glycerol
-
1-O-palmitoyl-2-O-linolenyl-3-O-(6'-deoxy-6'-sulfo-D-glucopyranosyl)-glycerol
-
3-(5-methyl-1H-imidazol-1-yl)-6-phenyl-2-sulfanylidene-2,3-dihydrothieno[2,3-d]pyrimidin-4(1H)-one
-
3-fluoro-3',4'-dimethoxy-N-[3-(4-methyl-1H-imidazol-1-yl)propyl][1,1'-biphenyl]-2-amine
-
3-[3-(5-methyl-1H-imidazol-1-yl)propyl]-2-sulfanylidene-2,3,5,6,7,8-hexahydro[1]benzothieno[2,3-d]pyrimidin-4(1H)-one
-
3-[3-(5-methyl-1H-imidazol-1-yl)propyl]-2-sulfanylidene-2,3-dihydroquinazolin-4(1H)-one
-
4'-fluoro-N-[3-(4-methyl-1H-imidazol-1-yl)propyl][1,1'-biphenyl]-2-amine
-
4-[2-[4-([1-[(3-aminophenyl)methyl]-1H-imidazol-2-yl]methyl)-1H-imidazol-1-yl]ethoxy]benzaldehyde
-
5-(5-[[(3,4-dimethoxyphenyl)sulfanyl]methyl]-1,3,4-oxadiazol-2-yl)-1H-benzimidazole
-
5-(5-[[(pyridin-4-yl)methyl]sulfanyl]-1,3,4-oxadiazol-2-yl)-1H-benzimidazole
-
N''-cyano-N-(2,3-dihydro-1,4-benzodioxin-6-yl)-N'-[3-(5-methyl-1H-imidazol-1-yl)propyl]guanidine
-
N''-cyano-N-(5-methyl-1H-imidazol-1-yl)-N'-(3,4,5-trimethoxyphenyl)guanidine
-
N''-cyano-N-methyl-N'-[3-(4-methyl-1H-imidazol-1-yl)propyl]guanidine
-
N''-cyano-N-methyl-N'-[3-(5-methyl-1H-imidazol-1-yl)propyl]guanidine
-
N-(2,3-dihydro-1,4-benzodioxin-6-yl)-N'-[3-(5-methyl-1H-imidazol-1-yl)propyl]thiourea
-
N-(3,4-dimethoxyphenyl)-N'-[3-(1H-imidazol-1-yl)-2-methylpropyl]thiourea
-
N-(3,4-dimethoxyphenyl)-N'-[3-(5-methyl-1H-imidazol-1-yl)propyl]thiourea
-
N-(3-methoxy-4-[[4-(piperidin-4-yl)phenyl]methoxy]phenyl)-N'-[3-(5-methyl-1H-imidazol-1-yl)propyl]thiourea
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N-(4-[(1E)-3-[4-(2-aminoethyl)piperazin-1-yl]-3-oxoprop-1-en-1-yl]phenyl)-N'-(5-methyl-1H-imidazol-1-yl)thiourea
-
N-[3-(4-aminobutoxy)-4-methoxyphenyl]-N'-[3-(2-methyl-1H-imidazol-1-yl)propyl]thiourea
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N-[3-methoxy-4-[(piperidin-4-yl)methoxy]phenyl]-N'-(5-methyl-1H-imidazol-1-yl)thiourea
-
N-[4-(2-aminoethoxy)-3-methoxyphenyl]-N'-(5-methyl-1H-imidazol-1-yl)thiourea
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N-[4-(3-aminopropoxy)-3-methoxyphenyl]-N'-(5-methyl-1H-imidazol-1-yl)thiourea
-
N-[4-(4-aminobutoxy)-3-methoxyphenyl]-N'-(5-methyl-1H-imidazol-1-yl)thiourea
-
N-[4-[3-(2-aminopyridin-4-yl)propoxy]-3-methoxyphenyl]-N'-(5-methyl-1H-imidazol-1-yl)thiourea
-
PQ529
can efficiently inhibit the activity of both glutaminyl cyclase isozymes QC and isoQC. Treatment with PQ529 for 48 h significantly blocks the binding of CC2C6 to the cell surface in a dosage-dependent manner in wild-type, but not in isoQC-deficient cells
(3,4-dichlorophenyl)-2-cyano-3-(3-(5-methyl-1H-imidazol-1-yl)propyl)guanidine
-
(3-(1H-imidazol-1-yl)propyl)-2-cyano-3-(2,3-dihydrobenzo[b][1,4]dioxin-7-yl)guanidine
-
(3-(1H-imidazol-1-yl)propyl)-2-cyano-3-(4-(trifluoromethyl)phenyl)guanidine
-
(3-(4-methyl-1H-imidazol-1-yl)propyl)-2-cyano-3-(2,3-dihydrobenzo[b][1,4]dioxin-7-yl)guanidine
-
(3-(5-methyl-1H-imidazol-1-yl)propyl)-2-cyano-3-(2,3-dihydrobenzo[b][1,4]dioxin-7-yl)guanidine
-
(E)-N1-(5-methyl-1H-imidazol-1-yl)-2-nitro-N'1-[4-(trifluoromethyl)phenyl]ethene-1,1-diamine
-
1-(3,4-dimethoxyphenyl)-3-(2-[1-(1H-imidazol-1-yl)cyclopropyl]ethyl)thiourea
-
-
1-(3,4-dimethoxyphenyl)-3-(3-(4-methyl-1H-imidazol-1-yl)propyl)thiourea
-
1-(3,4-dimethoxyphenyl)-3-(3-(5-methyl-1H-imidazol-1-yl)propyl)thiourea
-
1-(3,4-dimethoxyphenyl)-N-(1H-imidazol-1-yl)cyclopropane-1-carbothioamide
-
1-(3,4-dimethoxyphenyl)-N-(3-(4-methyl-1H-imidazol-1-yl)propyl)cyclopropanecarbothioamide
-
1-(3,4-dimethoxyphenyl)-N-(3-(5-methyl-1H-imidazol-1-yl)propyl)cyclopropanecarbothioamide
-
1-(3,4-dimethoxyphenyl)-N-(4-methyl-1H-imidazol-1-yl)cyclopropane-1-carbothioamide
-
1-(3,4-dimethoxyphenyl)-N-(5-methyl-1H-imidazol-1-yl)cyclopropane-1-carbothioamide
-
1-(3,4-dimethoxyphenyl)-N-[3-(1H-imidazol-1-yl)propyl]cyclopropane-1-carbothioamide
-
2,3-dihydro-3-(3-(4-methyl-1H-imidazol-1-yl)propyl)-2-thioxoquinazolin-4(1H)-one
-
2,3-dihydro-3-(3-(5-methyl-1H-imidazol-1-yl)propyl)-2-thioxoquinazolin-4(1H)-one
-
2,3-dihydro-6-methyl-3-(3-(5-methyl-1H-imidazol-1-yl)propyl)-5-phenyl-2-thioxothieno[2,3-d]pyrimidin-4(1H)-one
-
2-(2,3-dimethoxyphenyl)-5,7-dihydroxy-4H-chromen-4-one
87.7% inhibition at 0.1 mM
2-(2,3-dimethoxyphenyl)-7-hydroxy-4H-chromen-4-one
54.3% inhibition at 0.1 mM
2-(2,4-dimethoxyphenyl)-5,7-dihydroxy-4H-chromen-4-one
71.7% inhibition at 0.1 mM
2-(2-fluorophenyl)-5,7-dihydroxy-4H-chromen-4-one
84.2% inhibition at 0.1 mM
2-(3,4-dimethoxyphenyl)-7-hydroxy-4H-chromen-4-one
68.3% inhibition at 0.1 mM
2-(4-(dimethylamino)phenyl)-7-hydroxy-4H-chromen-4-one
90.3% inhibition at 0.1 mM
2-(4-ethoxyphenyl)-5,7-dihydroxy-4H-chromen-4-one
91.5% inhibition at 0.1 mM
2-(4-ethylphenyl)-5,7-dihydroxy-4H-chromen-4-one
85.2% inhibition at 0.1 mM
2-cyano(3,4,5-trimethoxyphenyl)-3-(3-(5-methyl-1H-imidazol-1-yl)propyl)guanidine
-
2-cyano(3-(5-methyl-1H-imidazol-1-yl)propyl)-3-(3,4-dimethylphenyl)guanidine
-
2-cyano-1-[3-(5-methyl-1H-imidazol-1-yl)propyl]-4-phenylbenzene-1-guanidine
-
3-(3-(1H-imidazol-1-yl)propyl)-2,3-dihydro-2-thioxoquinazolin-4(1H)-one
-
3-(3-(1H-imidazol-1-yl)propyl)-2,3-dihydro-7-methyl-2-thioxothieno[3,2-d]pyrimidin-4(1H)-one
-
3-(5-methyl-1H-imidazol-1-yl)-6-phenyl-2-sulfanylidene-2,3-dihydrothieno[2,3-d]pyrimidin-4(1H)-one
-
3-fluoro-3',4'-dimethoxy-N-[3-(4-methyl-1H-imidazol-1-yl)propyl][1,1'-biphenyl]-2-amine
-
3-[3-(1H-imidazol-1-yl)propyl]-2-thioxo-1,2,3,5,6,7-hexahydro-4H-cyclopenta[4,5]thieno[2,3-d]pyrimidin-4-one
-
3-[3-(1H-imidazol-1-yl)propyl]-2-thioxo-2,3,5,6,7,8,9,10-octahydrocycloocta[4,5]thieno[2,3-d]pyrimidin-4(1H)-one
-
3-[3-(1H-imidazol-1-yl)propyl]-2-thioxo-2,3,5,6,7,8-hexahydro[1]benzothieno[2,3-d]pyrimidin-4(1H)-one
-
3-[3-(5-methyl-1H-imidazol-1-yl)propyl]-2-sulfanylidene-2,3,5,6,7,8-hexahydro[1]benzothieno[2,3-d]pyrimidin-4(1H)-one
-
3-[3-(5-methyl-1H-imidazol-1-yl)propyl]-2-sulfanylidene-2,3-dihydroquinazolin-4(1H)-one
-
3-[3-(5-methyl-1H-imidazol-1-yl)propyl]-2-thioxo-2,3,5,6,7,8,9,10-octahydrocycloocta[4,5]-thieno[2,3-d]pyrimidin-4(1H)-one
-
3-[3-(5-methyl-1H-imidazol-1-yl)propyl]-2-thioxo-2,3,5,6,7,8-hexahydro[1]benzothieno[2,3-d]pyrimidin-4(1H)-one
-
4'-fluoro-N-[3-(4-methyl-1H-imidazol-1-yl)propyl][1,1'-biphenyl]-2-amine
-
4-[2-[4-([1-[(3-aminophenyl)methyl]-1H-imidazol-2-yl]methyl)-1H-imidazol-1-yl]ethoxy]benzaldehyde
-
5,6-dimethoxy-N-(3-(5-methyl-1H-imidazol-1-yl)propyl)-1Hbenzo[d]imidazol-2-amine
-
5,6-dimethoxy-N-[3-(5-methyl-1H-imidazol-1-yl)propyl]-1,3-benzothiazol-2-amine
-
5,6-dimethoxy-N-[3-(5-methyl-1H-imidazol-1-yl)propyl]-1H-benzimidazol-2-amine
-
5,7-dihydroxy-2-(3-methylthiophen-2-yl)-4H-chromen-4-one
91.6% inhibition at 0.1 mM
5,7-dihydroxy-2-(5-methylthiophen-2-yl)-4H-chromen-4-one
92.4% inhibition at 0.1 mM
5,7-dihydroxy-2-(thiophen-2-yl)-4H-chromen-4-one
92.6% inhibition at 0.1 mM
5-(5-[[(3,4-dimethoxyphenyl)sulfanyl]methyl]-1,3,4-oxadiazol-2-yl)-1H-benzimidazole
-
5-(5-[[(pyridin-4-yl)methyl]sulfanyl]-1,3,4-oxadiazol-2-yl)-1H-benzimidazole
-
6-benzyl-2,3-dihydro-3-(3-(5-methyl-1H-imidazol-1-yl)propyl)-2-thioxothieno[2,3-d]pyrimidin-4(1H)-one
-
7-hydroxy-2-(2-(trifluoromethyl)phenyl)-4H-chromen-4-one
70.8% inhibition at 0.1 mM
7-hydroxy-2-(2-methoxyphenyl)-4H-chromen-4-one
54.5% inhibition at 0.1 mM
7-hydroxy-2-(3,4,5-trimethoxyphenyl)-4H-chromen-4-one
68.7% inhibition at 0.1 mM
7-hydroxy-2-(4-(methylthio)phenyl)-4H-chromen-4-one
75.8% inhibition at 0.1 mM
7-hydroxy-2-(4-hydroxyphenyl)-4H-chromen-4-one
71.8% inhibition at 0.1 mM
7-hydroxy-2-(4-methoxyphenyl)-4H-chromen-4-one
75.2% inhibition at 0.1 mM
7-hydroxy-2-(5-methylfuran-2-yl)-4H-chromen-4-one
78.9% inhibition at 0.1 mM
diethyl dicarbonate
-
rapid inactivation by modification of three essential His residues, at neutral pH, partial reactivation with hydroxylamine
dipicolinic acid
inactivated enzyme can be fully restored by addition of Zn2+ in the presence of equimolar concentrations of EDTA, little reactivation by Co2+ and Mn2+
EFRH-NH2
-
competitive inhibitor with L-glutaminyl-7-amido-4-methylcumarin as substrate
EFRHHDSGYE-NH2
-
competitive inhibitor with L-glutaminyl-7-amido-4-methylcumarin as substrate
methyl N-[(2S)-1-hydroxy-2-[[3-(5-methyl-1H-imidazol-1-yl)propyl]amino]-3-phenylpropyl]-L-alaninate
-
N''-cyano-N-(2,3-dihydro-1,4-benzodioxin-6-yl)-N'-[3-(5-methyl-1H-imidazol-1-yl)propyl]guanidine
-
N''-cyano-N-(5-methyl-1H-imidazol-1-yl)-N'-(3,4,5-trimethoxyphenyl)guanidine
-
N''-cyano-N-methyl-N'-[3-(4-methyl-1H-imidazol-1-yl)propyl]guanidine
-
N''-cyano-N-methyl-N'-[3-(5-methyl-1H-imidazol-1-yl)propyl]guanidine
-
N-((E)-4-(3-(4-(2-aminoethyl)piperazin-1-yl)-3-oxoprop-1-en-1-yl)phenyl)-N'-(3-(5-methyl-1H-imidazol-1-yl)propyl)thiourea
-
N-((E)-4-(3-oxo-3-(piperazin-1-yl)prop-1-en-1-yl)phenyl)-N'-(3-(5-methyl-1H-imidazol-1-yl)propyl)thiourea
-
N-((E)-4-(3-oxo-3-(piperidin-4-ylamino)prop-1-en-1-yl)phenyl)-N'-(3-(5-methyl-1H-imidazol-1-yl)propyl)thiourea
-
N-(1-(3-(1H-imidazol-1-yl)propylamino)-2-nitrovinyl)-2,3-dihydrobenzo[b][1,4]-dioxin-6-amine
-
N-(1-(3-(1H-imidazol-1-yl)propylamino)-2-nitrovinyl)-3,4-dimethoxy-benzenamine
-
N-(1-(3-(1H-imidazol-1-yl)propylamino)-2-nitrovinyl)-4-(trifluoromethyl)-benzenamine
-
N-(1-(3-(1H-imidazol-1-yl)propylamino)-2-nitrovinyl)-4-chlorobenzenamine
-
N-(1-(3-(1H-imidazol-1-yl)propylamino)-2-nitrovinyl)-4-methoxybenzenamine
-
N-(1-(3-(4-methyl-1H-imidazol-1-yl)propylamino)-2-nitrovinyl)-2,3-dihydrobenzo[b][1,4]-dioxin-6-amine
-
N-(1-(3-(5-methyl-1H-imidazol-1-yl)propylamino)-2-nitrovinyl)-2,3-dihydrobenzo[b][1,4]-dioxin-6-amine
-
N-(1-(3-(5-methyl-1H-imidazol-1-yl)propylamino)-2-nitrovinyl)-4-(trifluoromethyl)benzenamine
-
N-(1-(3-(5-methyl-1H-imidazol-1-yl)propylamino)-2-nitrovinyl)-4-chloro-benzenamine
-
N-(1-(3-(5-methyl-1H-imidazol-1-yl)propylamino)-2-nitrovinyl)cyclohexanamine
-
N-(1-(3-(5-methyl-1H-imidazol-1-yl)propylamino)-2-nitrovinyl)naphthalen-1-amine
-
N-(2,3-dihydro-1,4-benzodioxin-6-yl)-N'-[3-(5-methyl-1H-imidazol-1-yl)propyl]thiourea
-
N-(3,4-dimethoxyphenyl)-4-[2-(5-methyl-1H-imidazol-1-yl)ethyl]-1,3-thiazol-2-amine
-
N-(3,4-dimethoxyphenyl)-5-[2-(5-methyl-1H-imidazol-1-yl)ethyl]-1,3,4-oxadiazol-2-amine
-
N-(3,4-dimethoxyphenyl)-N'-[3-(1H-imidazol-1-yl)-2-methylpropyl]thiourea
-
N-(3-(2-(2-aminopyridin-4-yl)ethoxy)-4-methoxyphenyl)-N'-(3-(5-methyl-1H-imidazol-1-yl)propyl)thiourea
-
N-(3-(2-aminoethoxy)-4-methoxyphenyl)-N'-(3-(5-methyl-1H-imidazol-1-yl)propyl)thiourea
-
N-(3-(3-(2-aminopyridin-4-yl)propoxy)-4-methoxyphenyl)-N'-(3-(5-methyl-1H-imidazol-1-yl)propyl)thiourea
-
N-(3-(3-aminopropoxy)-4-methoxyphenyl)-N'-(3-(5-methyl-1H-imidazol-1-yl)propyl)thiourea
-
N-(3-(4-(2-aminopyridin-4-yl)butoxy)-4-methoxyphenyl)-N'-(3-(5-methyl-1H-imidazol-1-yl)propyl)thiourea
-
N-(3-(4-(dimethylamino)butoxy)-4-methoxyphenyl)-N'-(3-(5-methyl-1H-imidazol-1-yl)propyl)thiourea
-
N-(3-(4-aminobutoxy)-4-methoxyphenyl)-N'-(3-(5-methyl-1H-imidazol-1-yl)propyl)thiourea
-
N-(3-methoxy-4-[[4-(piperidin-4-yl)phenyl]methoxy]phenyl)-N'-[3-(5-methyl-1H-imidazol-1-yl)propyl]thiourea
-
N-(4-((1-(2-aminoethyl)piperidin-4-yl)carbamoyl)phenyl)-N'-(3-(5-methyl-1H-imidazol-1-yl)propyl)thiourea
-
N-(4-(2-(((2-aminopyridin-4-yl)methyl)amino)-2-oxoethoxy)phenyl)-N'-(3-(5-methyl-1H-imidazol-1-yl)propyl)thiourea
-
N-(4-(2-((1-(2-aminoethyl)piperidin-4-yl)amino)-2-oxoethoxy)phenyl)-N'-(3-(5-methyl-1H-imidazol-1-yl)propyl)thiourea
-
N-(4-(2-(piperazin-1-yl)ethoxy)phenyl)-N'-(3-(5-methyl-1H-imidazol-1-yl)propyl)thiourea
-
N-(4-(2-oxo-2-(piperazin-1-yl)ethoxy)phenyl)-N'-(3-(5-methyl-1H-imidazol-1-yl)propyl)thiourea
-
N-(4-(2-oxo-2-(piperidin-4-ylamino)ethoxy)phenyl)-N'-(3-(5-methyl-1H-imidazol-1-yl)propyl)thiourea
-
N-(4-(4-(2-aminopyridin-4-yl)butoxy)phenyl)-N'-(3-(5-methyl-1H-imidazol-1-yl)propyl)thiourea
-
N-(4-chlorophenyl)-N'-[2-(1H-imidazol-1-yl)propyl]-2-thioxoimidazolidin-4-one
-
N-(4-methoxy-3-(2-(1-methylpiperidin-4-yl)ethoxy)phenyl)-N'-(3-(5-methyl-1H-imidazol-1-yl)propyl)thiourea
-
N-(4-methoxy-3-(2-(piperazin-1-yl)ethoxy)phenyl)-N'-(3-(5-methyl-1H-imidazol-1-yl)propyl)thiourea
-
N-(4-methoxy-3-(2-(piperidin-4-yl)ethoxy)phenyl)-N'-(3-(5-methyl-1H-imidazol-1-yl)propyl)thiourea
-
N-(4-methoxy-3-(3-(methylamino)propoxy)phenyl)-N'-(3-(5-methyl-1H-imidazol-1-yl)propyl)thiourea
-
N-(4-methoxy-3-(3-(piperazin-1-yl)propoxy)phenyl)-N'-(3-(5-methyl-1H-imidazol-1-yl)propyl)thiourea
-
N-(4-methoxy-3-(3-(piperidin-4-yl)propoxy)phenyl)-N'-(3-(5-methyl-1H-imidazol-1-yl)propyl)thiourea
-
N-(4-methoxy-3-(4-(methylamino)butoxy)phenyl)-N'-(3-(5-methyl-1H-imidazol-1-yl)propyl)thiourea
-
N-(4-methoxy-3-(4-(piperazin-1-yl)butoxy)phenyl)-N'-(3-(5-methyl-1H-imidazol-1-yl)propyl)thiourea
-
N-(4-methoxy-3-(4-(piperidin-4-yl)butoxy)phenyl)-N'-(3-(5-methyl-1H-imidazol-1-yl)propyl)thiourea
-
N-(4-methoxy-3-(4-(pyrimidin-2-ylamino)butoxy)phenyl)-N'-(3-(5-methyl-1H-imidazol-1-yl)propyl)thiourea
-
N-(4-[(1E)-3-[4-(2-aminoethyl)piperazin-1-yl]-3-oxoprop-1-en-1-yl]phenyl)-N'-(5-methyl-1H-imidazol-1-yl)thiourea
-
N-(E)-(4-(3-(4-(2-aminoethyl)piperazin-1-yl)-3-oxoprop-1-en-1-yl)phenyl)-N'-(3-(5-methyl-1H-imidazol-1-yl)propyl)thiourea
-
N-[3-(4-aminobutoxy)-4-methoxyphenyl]-N'-[3-(2-methyl-1H-imidazol-1-yl)propyl]thiourea
-
N-[3-methoxy-4-[(piperidin-4-yl)methoxy]phenyl]-N'-(5-methyl-1H-imidazol-1-yl)thiourea
-
N-[4-(2-aminoethoxy)-3-methoxyphenyl]-N'-(5-methyl-1H-imidazol-1-yl)thiourea
-
N-[4-(3-aminopropoxy)-3-methoxyphenyl]-N'-(5-methyl-1H-imidazol-1-yl)thiourea
-
N-[4-(4-aminobutoxy)-3-methoxyphenyl]-N'-(5-methyl-1H-imidazol-1-yl)thiourea
-
N-[4-[3-(2-aminopyridin-4-yl)propoxy]-3-methoxyphenyl]-N'-(5-methyl-1H-imidazol-1-yl)thiourea
-
N2-[(2S)-1-hydroxy-2-[[3-(5-methyl-1H-imidazol-1-yl)propyl]amino]-3-phenylpropyl]-L-alaninamide
-
SEN-177
the triazole based inhibitor, SEN177 coordinates with the catalytically important Zn2+ ion of sQC and has made several hydrophobic interactions with active site residues such as W207, F325, and W329
SEN177
i.e. 6''-fluoro-4-(4-methyl-4H-[1,2,4]triazol-3-yl)-3,4,5,6-tetrahydro-2H-[1,2',3',3'']terpyridine, binding structure with Golgi-resident hQC
1,10-phenanthroline
inactivated enzyme can be fully restored by addition of Zn2+ in the presence of equimolar concentrations of EDTA, little reactivation by Co2+ and Mn2+
1,2-di-O-palmitoyl-3-O-(6'-deoxy-6'-sulfo-D-glycopyranosyl)-glycerol
-
1-(3,4-dimethoxyphenyl)-3-[3-(1H-imidazol-1-yl)propyl]thiourea
-
i.e. P150/03, complete inhibition at 0.01 mM
1-O-linolyl-2-O-palmitoyl-3-O-(6'-deoxy-6'-sulfo-D-glucopyranosyl)-glycerol
-
1-O-linolyl-2-O-palmitoyl-3-O-(6'-deoxy-6'-sulfo-D-glucopyranosyl)-glycerol
-
1-O-palmitoyl-2-O-linolenyl-3-O-(6'-deoxy-6'-sulfo-D-glucopyranosyl)-glycerol
-
1-O-palmitoyl-2-O-linolenyl-3-O-(6'-deoxy-6'-sulfo-D-glucopyranosyl)-glycerol
-
N-(3,4-dimethoxyphenyl)-N'-[3-(5-methyl-1H-imidazol-1-yl)propyl]thiourea
-
N-(3,4-dimethoxyphenyl)-N'-[3-(5-methyl-1H-imidazol-1-yl)propyl]thiourea
-
N-(3,4-dimethoxyphenyl)-N'-[3-(5-methyl-1H-imidazol-1-yl)propyl]thiourea
-
SEN177
i.e. 6''-fluoro-4-(4-methyl-4H-[1,2,4]triazol-3-yl)-3,4,5,6-tetrahydro-2H-[1,2',3',3'']terpyridine, binding structure with secretory hQC
additional information
crystal structures of weak binding inhibitors of human QC isozymes, share the imidazole ring as the Zn(II) binding moiety, overview
-
additional information
crystal structures of weak binding inhibitors of human QC isozymes, share the imidazole ring as the Zn(II) binding moiety, overview
-
additional information
-
crystal structures of weak binding inhibitors of human QC isozymes, share the imidazole ring as the Zn(II) binding moiety, overview
-
additional information
development of small molecule inhibitors of glutaminyl cyclase and isoglutaminyl cyclase for Alzheimers disease, overview. Weak inhibition by imidazole derivatives
-
additional information
development of small molecule inhibitors of glutaminyl cyclase and isoglutaminyl cyclase for Alzheimers disease, overview. Weak inhibition by imidazole derivatives
-
additional information
structure-function analysis of enzyme inhibitors, overview
-
additional information
structure-function analysis of enzyme inhibitors, overview
-
additional information
-
structure-function analysis of enzyme inhibitors, overview
-
additional information
crystal structures of weak binding inhibitors of human QC isozymes, all share the imidazole ring as the Zn(II) binding moiety, overview
-
additional information
crystal structures of weak binding inhibitors of human QC isozymes, all share the imidazole ring as the Zn(II) binding moiety, overview
-
additional information
-
crystal structures of weak binding inhibitors of human QC isozymes, all share the imidazole ring as the Zn(II) binding moiety, overview
-
additional information
development of small molecule inhibitors of glutaminyl cyclase and isoglutaminyl cyclase for Alzheimers disease, overview
-
additional information
development of small molecule inhibitors of glutaminyl cyclase and isoglutaminyl cyclase for Alzheimers disease, overview
-
additional information
in vitro and in silico determination of glutaminyl cyclase inhibitors, heterocyclic and peptidomimetic derivatives are synthesized and are able to inhibit the hQC enzyme, overview. The binding mechanism at the atomic level is estimated using molecular docking, free energy perturbation, and quantum chemical calculation methods. The predicted log(BBB) and human intestinal absorption values indicated that these compounds are able to permeate the blood-brain barrier and be well-absorbed through the gastrointestinal tract. Molecular docking study and atomistic molecular dynamics simulations, overview
-
additional information
natural products from microalgae, such as Scenedesmus rubescens strain SAG 5.95, Scenedesmus producto-capitatus strain SAG 21.81, Scenedesmus accuminatus strain SAG 38.81, Scenedesmus pectinatus strain SAG 2003, Tetradesmus wisconsinensis strain SAG 3.99, and Eustigmatos magnus strain SAG 36.89, show potential against Alzheimers disease, sulfolipids are potent glutaminyl cyclase inhibitors. Mass spectrometric identification and analysis (high resolution ESI-FTIC-MS and UPLC-MS, UPLC/ESI-MSn measurements). The sulfolipids share common, necessary substructures with pharmacophore characteristics of known QC inhibitors
-
additional information
phenol-40 (R1-), C5-OH (R2-) and C7-OH (R3-) modified apigenin derivatives are synthesized and evaluated as human QC (hQC) inhibitors, structure-function analysis, molecular docking, overview. No inhibition by 7-methoxy-2-(3-methylthiophen-2-yl)-4H-chromen-4-one, 7-methoxy-2-(4-methoxyphenyl)-4H-chromen-4-one, 7-methoxy-2-(2-methoxyphenyl)-4H-chromen-4-one, 2-(3,4-dimethoxyphenyl)-7-methoxy-4H-chromen-4-one, 7-methoxy-2-(3,4,5-trimethoxyphenyl)-4H-chromen-4-one, 2-(4-fluorophenyl)-7-methoxy-4H-chromen-4-one, 2-(3-fluorophenyl)-7-methoxy-4H-chromen-4-one, 7-methoxy-2-(2-(trifluoromethyl)phenyl)-4H-chromen-4-one, 7-methoxy-2-(pyridin-3-yl)-4H-chromen-4-one, 2-(furan-2-yl)-7-methoxy-4H-chromen-4-one, and 2-(furan-3-yl)-7-methoxy-4H-chromen-4-one
-
additional information
-
phenol-40 (R1-), C5-OH (R2-) and C7-OH (R3-) modified apigenin derivatives are synthesized and evaluated as human QC (hQC) inhibitors, structure-function analysis, molecular docking, overview. No inhibition by 7-methoxy-2-(3-methylthiophen-2-yl)-4H-chromen-4-one, 7-methoxy-2-(4-methoxyphenyl)-4H-chromen-4-one, 7-methoxy-2-(2-methoxyphenyl)-4H-chromen-4-one, 2-(3,4-dimethoxyphenyl)-7-methoxy-4H-chromen-4-one, 7-methoxy-2-(3,4,5-trimethoxyphenyl)-4H-chromen-4-one, 2-(4-fluorophenyl)-7-methoxy-4H-chromen-4-one, 2-(3-fluorophenyl)-7-methoxy-4H-chromen-4-one, 7-methoxy-2-(2-(trifluoromethyl)phenyl)-4H-chromen-4-one, 7-methoxy-2-(pyridin-3-yl)-4H-chromen-4-one, 2-(furan-2-yl)-7-methoxy-4H-chromen-4-one, and 2-(furan-3-yl)-7-methoxy-4H-chromen-4-one
-
additional information
structure-activity relationship analysis of Phe-Arg mimetic region of human glutaminyl cyclase inhibitors. Developed of QC inhibitors that contain 3-aminoalkyloxy-4-methoxyphenyl and 4-aminoalkyloxyphenyl groups to replace the previously developed pharmacophore, overview. In vivo activity of the compounds is analyzed using HT-22 cells, an immortalized hippocampal neuronal cell line
-
additional information
-
structure-activity relationship analysis of Phe-Arg mimetic region of human glutaminyl cyclase inhibitors. Developed of QC inhibitors that contain 3-aminoalkyloxy-4-methoxyphenyl and 4-aminoalkyloxyphenyl groups to replace the previously developed pharmacophore, overview. In vivo activity of the compounds is analyzed using HT-22 cells, an immortalized hippocampal neuronal cell line
-
additional information
structure-function analysis of enzyme inhibitors, overview. Natural products and their derivatives belonging to the sulfolipid family and isolated from methanol extracts of different algae species (such as Scenedesmus rubescens, Scenedesmus producto-capitatus, Scenedesmus accuminatus, Scenedesmus pectinatus, Tetradesmus wisconsinensis, and Eustigmatos magnusa) act as inhibitors of sQC. Synthesis and evaluation of benzimidazole based inhibitors, overview
-
additional information
structure-function analysis of enzyme inhibitors, overview. Natural products and their derivatives belonging to the sulfolipid family and isolated from methanol extracts of different algae species (such as Scenedesmus rubescens, Scenedesmus producto-capitatus, Scenedesmus accuminatus, Scenedesmus pectinatus, Tetradesmus wisconsinensis, and Eustigmatos magnusa) act as inhibitors of sQC. Synthesis and evaluation of benzimidazole based inhibitors, overview
-
additional information
-
structure-function analysis of enzyme inhibitors, overview. Natural products and their derivatives belonging to the sulfolipid family and isolated from methanol extracts of different algae species (such as Scenedesmus rubescens, Scenedesmus producto-capitatus, Scenedesmus accuminatus, Scenedesmus pectinatus, Tetradesmus wisconsinensis, and Eustigmatos magnusa) act as inhibitors of sQC. Synthesis and evaluation of benzimidazole based inhibitors, overview
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.1
Gln-Phe-Ala
-
protein version: shortened N-terminus, I73N/C369A, His-tagged, pH 8.0, 30°C, similar value with other protein versions
0.06
L-glutaminyl-2-naphthylamide
-
30°C, recombinant enzyme, expressed in Pichia pastoris
0.051
L-glutaminyl-4-methylcoumarinylamide
-
30°C, recombinant enzyme, expressed in Pichia pastoris
0.03
L-glutaminyl-7-amido-4-methylcoumarin
-
protein version: shortened N-terminus, I73N/C369A, His-tagged, pH 8.0, 30°C, similar value with other protein versions
0.035
L-glutaminyl-beta-naphthylamide
-
protein version: shortened N-terminus, I73N/C369A, His-tagged, pH 8.0, 30°C, similar value with other protein versions
0.16
QEDL
-
protein version: shortened N-terminus, I73N/C369A, His-tagged, pH 8.0, 30°C, similar value with other protein versions
0.04
QEYF
-
protein version: shortened N-terminus, I73N/C369A, His-tagged, pH 8.0, 30°C, similar value with other protein versions
0.087
Gln(3)-amyloid-beta peptide 3-11 amide
-
pH 6.0, 30°C, in absence of DMSO
-
0.11
Gln-Gln
-
protein version: shortened N-terminus, I73N/C369A, His-tagged, pH 8.0, 30°C, similar value with other protein versions
0.61
Gln-Glu
-
protein version: shortened N-terminus, I73N/C369A, His-tagged, pH 8.0, 30°C, similar value with other protein versions
0.36
Gln-Gly
-
protein version: shortened N-terminus, I73N/C369A, His-tagged, pH 8.0, 30°C, similar value with other protein versions
0.23
Gln-Gly-Pro
-
protein version: shortened N-terminus, I73N/C369A, His-tagged, pH 8.0, 30°C, similar value with other protein versions
0.08
Gln-Tyr-Ala
-
protein version: shortened N-terminus, I73N/C369A, His-tagged, pH 8.0, 30°C, similar value with other protein versions
additional information
additional information
Michaelis-Menten kinetics
-
additional information
additional information
Michaelis-Menten kinetics
-
additional information
additional information
Michaelis-Menten kinetics
-
additional information
additional information
Michaelis-Menten kinetics
-
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
7.5
Gln-Phe-Ala
-
protein version: shortened N-terminus, I73N/C369A, His-tagged, pH 8.0, 30°C, similar value with other protein versions
18.8
L-glutaminyl-2-naphthylamide
-
30°C, recombinant enzyme, expressed in Pichia pastoris
5.4
L-glutaminyl-4-methylcoumarinylamide
-
30°C, recombinant enzyme, expressed in Pichia pastoris
1.07
L-glutaminyl-7-amido-4-methylcoumarin
-
protein version: shortened N-terminus, I73N/C369A, His-tagged, pH 8.0, 30°C, similar value with other protein versions
3.4
L-glutaminyl-beta-naphthylamide
-
protein version: shortened N-terminus, I73N/C369A, His-tagged, pH 8.0, 30°C, similar value with other protein versions
6.4
QEDL
-
protein version: shortened N-terminus, I73N/C369A, His-tagged, pH 8.0, 30°C, similar value with other protein versions
3.3
QEYF
-
protein version: shortened N-terminus, I73N/C369A, His-tagged, pH 8.0, 30°C, similar value with other protein versions
2.7
Gln-Gln
-
protein version: shortened N-terminus, I73N/C369A, His-tagged, pH 8.0, 30°C, similar value with other protein versions
2.6
Gln-Glu
-
protein version: shortened N-terminus, I73N/C369A, His-tagged, pH 8.0, 30°C, similar value with other protein versions
1.65
Gln-Gly
-
protein version: shortened N-terminus, I73N/C369A, His-tagged, pH 8.0, 30°C, similar value with other protein versions
4
Gln-Gly-Pro
-
protein version: shortened N-terminus, I73N/C369A, His-tagged, pH 8.0, 30°C, similar value with other protein versions
7.7
Gln-Tyr-Ala
-
protein version: shortened N-terminus, I73N/C369A, His-tagged, pH 8.0, 30°C, similar value with other protein versions
kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
54
Gln-Gln
-
protein version: shortened N-terminus, I73N/C369A, His-tagged, pH 8.0, 30°C, similar value with other protein versions
9
Gln-Glu
-
protein version: shortened N-terminus, I73N/C369A, His-tagged, pH 8.0, 30°C, similar value with other protein versions
9
Gln-Gly
-
protein version: shortened N-terminus, I73N/C369A, His-tagged, pH 8.0, 30°C, similar value with other protein versions
38
Gln-Gly-Pro
-
protein version: shortened N-terminus, I73N/C369A, His-tagged, pH 8.0, 30°C, similar value with other protein versions
117
Gln-Phe-Ala
-
protein version: shortened N-terminus, I73N/C369A, His-tagged, pH 8.0, 30°C, similar value with other protein versions
207
Gln-Tyr-Ala
-
protein version: shortened N-terminus, I73N/C369A, His-tagged, pH 8.0, 30°C, similar value with other protein versions
103
L-glutaminyl-7-amido-4-methylcoumarin
-
protein version: shortened N-terminus, I73N/C369A, His-tagged, pH 8.0, 30°C, similar value with other protein versions
229
L-glutaminyl-beta-naphthylamide
-
protein version: shortened N-terminus, I73N/C369A, His-tagged, pH 8.0, 30°C, similar value with other protein versions
55
QEDL
-
protein version: shortened N-terminus, I73N/C369A, His-tagged, pH 8.0, 30°C, similar value with other protein versions
123
QEYF
-
protein version: shortened N-terminus, I73N/C369A, His-tagged, pH 8.0, 30°C, similar value with other protein versions
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.000262
1-Benzylimidazole
Golgi-resident glutaminyl cyclase, at 25°C in 50 mM Tris-HCl, pH 8.0
6.696
cacodylate
Golgi-resident glutaminyl cyclase, at 25°C in 50 mM Tris-HCl, pH 8.0
0.005748
Nomega-acetylhistamine
Golgi-resident glutaminyl cyclase, at 25°C in 50 mM Tris-HCl, pH 8.0
0.001817
PBD150
Golgi-resident glutaminyl cyclase, at 25°C in 50 mM Tris-HCl, pH 8.0
0.253
(3,4-dichlorophenyl)-2-cyano-3-(3-(5-methyl-1H-imidazol-1-yl)propyl)guanidine
-
0.62
(3-(1H-imidazol-1-yl)propyl)-2-cyano-3-(2,3-dihydrobenzo[b][1,4]dioxin-7-yl)guanidine
-
1.36
(3-(1H-imidazol-1-yl)propyl)-2-cyano-3-(3,4-dimethoxyphenyl)guanidine
-
6.72
(3-(1H-imidazol-1-yl)propyl)-2-cyano-3-(4-(trifluoromethyl)phenyl)guanidine
-
0.83
(3-(1H-imidazol-1-yl)propyl)-2-cyano-3-(4-isopropylphenyl)guanidine
-
1.37
(3-(1H-imidazol-1-yl)propyl)-2-cyano-3-(cyclopropylmethyl)guanidine
-
1.65
(3-(4-methyl-1H-imidazol-1-yl)propyl)-2-cyano-3-(2,3-dihydrobenzo[b][1,4]dioxin-7-yl)guanidine
-
0.13
(3-(5-methyl-1H-imidazol-1-yl)propyl)-2-cyano-3-(2,3-dihydrobenzo[b][1,4]dioxin-7-yl)guanidine
-
0.00112
1-(2,3-dihydro-1,4-benzodioxin-6-yl)-3-[3-(1H-imidazol-1-yl)propyl]thiourea
-
pH 8.0, 30°C
0.00056
1-(2,4-dimethoxyphenyl)-3-[3-(1H-imidazol-1-yl)propyl]thiourea
-
pH 8.0, 30°C
0.00155
1-(3,4-dimethoxybenzyl)-3-[3-(1H-imidazol-1-yl)propyl]thiourea
-
pH 8.0, 30°C
0.00233
1-(3,4-dimethoxyphenyl)-3-(2-[1-(1H-imidazol-1-yl)cyclopropyl]ethyl)thiourea
-
pH 8.0, 30°C
0.06
1-(3,4-dimethoxyphenyl)-3-(3-(4-methyl-1H-imidazol-1-yl)propyl)thiourea
-
0.0063
1-(3,4-dimethoxyphenyl)-3-(3-(5-methyl-1H-imidazol-1-yl)propyl)thiourea
-
0.00034
1-(3,4-dimethoxyphenyl)-3-[(3R)-3-(1H-imidazol-1-yl)butyl]thiourea
-
pH 8.0, 30°C
0.00076
1-(3,4-dimethoxyphenyl)-3-[(3S)-3-(1H-imidazol-1-yl)butyl]thiourea
-
pH 8.0, 30°C
0.00006
1-(3,4-dimethoxyphenyl)-3-[3-(1H-imidazol-1-yl)propyl]thiourea
-
pH 8.0, 30°C
0.00049
1-(3,4-dimethoxyphenyl)-3-[3-(1H-imidazol-1-yl)propyl]urea
-
pH 8.0, 30°C
0.00055
1-(3,4-dimethoxyphenyl)-3-[4-(1H-imidazol-1-yl)butyl]thiourea
-
pH 8.0, 30°C
0.041
1-(3,4-dimethoxyphenyl)-N-(3-(4-methyl-1H-imidazol-1-yl)propyl)cyclopropanecarbothioamide
-
0.0026
1-(3,4-dimethoxyphenyl)-N-(3-(5-methyl-1H-imidazol-1-yl)propyl)cyclopropanecarbothioamide
-
0.00075
1-(3,5-dimethoxyphenyl)-3-[3-(1H-imidazol-1-yl)propyl]thiourea
-
pH 8.0, 30°C
0.00089
1-(4-ethoxyphenyl)-3-[3-(1H-imidazol-1-yl)propyl]thiourea
-
pH 8.0, 30°C
0.00034
1-[3-(1H-imidazol-1-yl)propyl]-3-(3,4,5-trimethoxyphenyl)thiourea
-
pH 8.0, 30°C
0.00186
1-[3-(1H-imidazol-1-yl)propyl]-3-(3-methoxyphenyl)thiourea
-
pH 8.0, 30°C
0.0007
1-[3-(1H-imidazol-1-yl)propyl]-3-(4-methoxyphenyl)thiourea
-
pH 8.0, 30°C
0.00214
1-[3-(1H-imidazol-1-yl)propyl]-3-(4-methylphenyl)thiourea
-
pH 8.0, 30°C
0.00166
1-[3-(1H-imidazol-1-yl)propyl]-3-[4-(methylthio)phenyl]thiourea
-
pH 8.0, 30°C
0.00097
1-[4-(benzyloxy)phenyl]-3-[3-(1H-imidazol-1-yl)propyl]thiourea
-
pH 8.0, 30°C
0.23
2,3-dihydro-3-(3-(4-methyl-1H-imidazol-1-yl)propyl)-2-thioxoquinazolin-4(1H)-one
-
0.018
2,3-dihydro-3-(3-(5-methyl-1H-imidazol-1-yl)propyl)-2-thioxoquinazolin-4(1H)-one
-
0.083
2,3-dihydro-6-methyl-3-(3-(5-methyl-1H-imidazol-1-yl)propyl)-5-phenyl-2-thioxothieno[2,3-d]pyrimidin-4(1H)-one
-
0.061
2-cyano(3,4,5-trimethoxyphenyl)-3-(3-(5-methyl-1H-imidazol-1-yl)propyl)guanidine
-
0.082
2-cyano(3-(5-methyl-1H-imidazol-1-yl)propyl)-3-(3,4-dimethylphenyl)guanidine
-
0.065
2-cyano-1-[3-(5-methyl-1H-imidazol-1-yl)propyl]-4-phenylbenzene-1-guanidine
-
0.3
3-(3-(1H-imidazol-1-yl)propyl)-2,3-dihydro-2-thioxoquinazolin-4(1H)-one
-
0.36
3-(3-(1H-imidazol-1-yl)propyl)-2,3-dihydro-7-methyl-2-thioxothieno[3,2-d]pyrimidin-4(1H)-one
-
0.62
3-[3-(1H-imidazol-1-yl)propyl]-2-thioxo-1,2,3,5,6,7-hexahydro-4H-cyclopenta[4,5]thieno[2,3-d]pyrimidin-4-one
-
0.9
3-[3-(1H-imidazol-1-yl)propyl]-2-thioxo-2,3,5,6,7,8,9,10-octahydrocycloocta[4,5]thieno[2,3-d]pyrimidin-4(1H)-one
-
0.34
3-[3-(1H-imidazol-1-yl)propyl]-2-thioxo-2,3,5,6,7,8-hexahydro[1]benzothieno[2,3-d]pyrimidin-4(1H)-one
-
0.818
3-[3-(1H-imidazol-1-yl)propyl]-2-thioxoimidazolidin-4-one
30°C, pH 8.0
0.039
3-[3-(5-methyl-1H-imidazol-1-yl)propyl]-2-thioxo-2,3,5,6,7,8,9,10-octahydrocycloocta[4,5]-thieno[2,3-d]pyrimidin-4(1H)-one
-
0.017
3-[3-(5-methyl-1H-imidazol-1-yl)propyl]-2-thioxo-2,3,5,6,7,8-hexahydro[1]benzothieno[2,3-d]pyrimidin-4(1H)-one
-
0.000023
5-(5-[[(3,4-dimethoxyphenyl)sulfanyl]methyl]-1,3,4-oxadiazol-2-yl)-1H-benzimidazole
pH and temperature not specified in the publication
0.00101
5-(5-[[(pyridin-4-yl)methyl]sulfanyl]-1,3,4-oxadiazol-2-yl)-1H-benzimidazole
pH and temperature not specified in the publication
0.000638
5-[5-(2-phenylethyl)-1,3,4-oxadiazol-2-yl]-1H-benzimidazole
pH and temperature not specified in the publication
0.02
6-benzyl-2,3-dihydro-3-(3-(5-methyl-1H-imidazol-1-yl)propyl)-2-thioxothieno[2,3-d]pyrimidin-4(1H)-one
-
1.824
cacodylate
secretory glutaminyl cyclase, at 25°C in 50 mM Tris-HCl, pH 8.0
4.47
L-glutaminyl-7-amido-4-methylcoumarin
-
protein version: shortened N-terminus, I73N/C369A, His-tagged, pH 8.0, 30°C, similar value with other protein versions
1.57
L-glutaminyl-beta-naphthylamide
-
protein version: shortened N-terminus, I73N/C369A, His-tagged, pH 8.0, 30°C, similar value with other protein versions
0.051
N-(-1-(3-(5-methyl-1H-imidazol-1-yl)propylamino)-2-nitrovinyl)-4-chloro-benzenamine
-
0.54
N-(1-(3-(1H-imidazol-1-yl)propylamino)-2-nitrovinyl)-2,3-dihydrobenzo[b][1,4]-dioxin-6-amine
-
0.61
N-(1-(3-(1H-imidazol-1-yl)propylamino)-2-nitrovinyl)-3,4-dimethoxy-benzenamine
-
0.54
N-(1-(3-(1H-imidazol-1-yl)propylamino)-2-nitrovinyl)-4-(trifluoromethyl)-benzenamine
-
0.57
N-(1-(3-(1H-imidazol-1-yl)propylamino)-2-nitrovinyl)-4-chlorobenzenamine
-
1.03
N-(1-(3-(1H-imidazol-1-yl)propylamino)-2-nitrovinyl)-4-methoxybenzenamine
-
0.52
N-(1-(3-(1H-imidazol-1-yl)propylamino)-2-nitrovinyl)naphthalen-1-amine
-
1.29
N-(1-(3-(4-methyl-1H-imidazol-1-yl)propylamino)-2-nitrovinyl)-2,3-dihydrobenzo[b][1,4]-dioxin-6-amine
-
0.067
N-(1-(3-(5-methyl-1H-imidazol-1-yl)propylamino)-2-nitrovinyl)-2,3-dihydrobenzo[b][1,4]-dioxin-6-amine
-
0.034
N-(1-(3-(5-methyl-1H-imidazol-1-yl)propylamino)-2-nitrovinyl)-4-(trifluoromethyl)benzenamine
-
0.044
N-(1-(3-(5-methyl-1H-imidazol-1-yl)propylamino)-2-nitrovinyl)cyclohexanamine
-
0.042
N-(1-(3-(5-methyl-1H-imidazol-1-yl)propylamino)-2-nitrovinyl)naphthalen-1-amine
-
0.000006
N-(3,4-dimethoxyphenyl)-N'-[3-(1H-imidazol-1-yl)propyl]thiourea
pH and temperature not specified in the publication
0.5
N-(3-(1H-imidazol-1-yl)propyl)-N-cyclohexyl-2-nitroethene-1,1-diamine
-
20.55
N-(3-(1H-imidazol-1-yl)propyl)-N-methyl-2-nitroethene-1,1-diamine
-
0.0012
N-(4-chlorophenyl)-N'-[2-(1H-imidazol-1-yl)propyl]-2-thioxoimidazolidin-4-one
30°C, pH 8.0
0.00124
N-(4-chlorophenyl)-N'-[3-(1H-imidazol-1-yl)propyl]thiourea
pH and temperature not specified in the publication
0.002
N-[3-(1H-imidazol-1-yl)propyl]-5-methoxy-1,3-benzothiazol-2-amine
-
pH 8.0, 30°C
0.00157
N-[3-(1H-imidazol-1-yl)propyl]-6-methoxy-1,3-benzothiazol-2-amine
-
pH 8.0, 30°C
0.001698
Nomega-acetylhistamine
secretory glutaminyl cyclase, at 25°C in 50 mM Tris-HCl, pH 8.0
0.000607
1-Benzylimidazole
secretory glutaminyl cyclase, at 25°C in 50 mM Tris-HCl, pH 8.0
0.25
benzimidazole
-
protein version: shortened N-terminus, I73N/C369A, His-tagged, pH 8.0, 30°C, similar value with other protein versions
0.0062
benzylimidazole
-
protein version: shortened N-terminus, I73N/C369A, His-tagged, pH 8.0, 30°C, similar value with other protein versions
0.235
imidazole
-
protein version: shortened N-terminus, I73N/C369A, His-tagged, pH 8.0, 30°C, similar value with other protein versions
0.082
methylimidazole
-
protein version: shortened N-terminus, I73N/C369A, His-tagged, pH 8.0, 30°C, similar value with other protein versions
0.000095
PBD150
secretory glutaminyl cyclase, at 25°C in 50 mM Tris-HCl, pH 8.0
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.000013
SEN177
Homo sapiens
pH and temperature not specified in the publication
0.000058
Sen180
Homo sapiens
pH and temperature not specified in the publication
0.0003
5,6-dimethoxy-N-[3-(5-methyl-1H-imidazol-1-yl)propyl]-1,3-benzothiazol-2-amine
Homo sapiens
pH 7.0, 37°C
0.00011
5,6-dimethoxy-N-[3-(5-methyl-1H-imidazol-1-yl)propyl]-1H-benzimidazol-2-amine
Homo sapiens
pH 7.0, 37°C
0.00007
5-(5-[[(3,4-dimethoxyphenyl)sulfanyl]methyl]-1,3,4-oxadiazol-2-yl)-1H-benzimidazole
Homo sapiens
pH and temperature not specified in the publication
0.00396
5-[5-(2-phenylethyl)-1,3,4-oxadiazol-2-yl]-1H-benzimidazole
Homo sapiens
pH and temperature not specified in the publication
0.00064
methyl N-[(2S)-1-hydroxy-2-[[3-(5-methyl-1H-imidazol-1-yl)propyl]amino]-3-phenylpropyl]-L-alaninate
Homo sapiens
pH 7.0, 37°C
0.0000064
N-((E)-4-(3-(4-(2-aminoethyl)piperazin-1-yl)-3-oxoprop-1-en-1-yl)phenyl)-N'-(3-(5-methyl-1H-imidazol-1-yl)propyl)thiourea
Homo sapiens
pH and temperature not specified in the publication
0.0000194
N-((E)-4-(3-oxo-3-(piperazin-1-yl)prop-1-en-1-yl)phenyl)-N'-(3-(5-methyl-1H-imidazol-1-yl)propyl)thiourea
Homo sapiens
pH and temperature not specified in the publication
0.000026
N-((E)-4-(3-oxo-3-(piperidin-4-ylamino)prop-1-en-1-yl)phenyl)-N'-(3-(5-methyl-1H-imidazol-1-yl)propyl)thiourea
Homo sapiens
pH and temperature not specified in the publication
0.00032
N-(3,4-dimethoxyphenyl)-4-[2-(5-methyl-1H-imidazol-1-yl)ethyl]-1,3-thiazol-2-amine
Homo sapiens
pH 7.0, 37°C
0.00042
N-(3,4-dimethoxyphenyl)-5-[2-(5-methyl-1H-imidazol-1-yl)ethyl]-1,3,4-oxadiazol-2-amine
Homo sapiens
pH 7.0, 37°C
0.000029 - 0.0000292
N-(3,4-dimethoxyphenyl)-N'-[3-(5-methyl-1H-imidazol-1-yl)propyl]thiourea
0.0000264
N-(3-(2-(2-aminopyridin-4-yl)ethoxy)-4-methoxyphenyl)-N'-(3-(5-methyl-1H-imidazol-1-yl)propyl)thiourea
Homo sapiens
pH and temperature not specified in the publication
0.0000079
N-(3-(2-aminoethoxy)-4-methoxyphenyl)-N'-(3-(5-methyl-1H-imidazol-1-yl)propyl)thiourea
Homo sapiens
pH and temperature not specified in the publication
0.000015
N-(3-(3-(2-aminopyridin-4-yl)propoxy)-4-methoxyphenyl)-N'-(3-(5-methyl-1H-imidazol-1-yl)propyl)thiourea
Homo sapiens
pH and temperature not specified in the publication
0.000009
N-(3-(3-aminopropoxy)-4-methoxyphenyl)-N'-(3-(5-methyl-1H-imidazol-1-yl)propyl)thiourea
Homo sapiens
pH and temperature not specified in the publication
0.0000159
N-(3-(4-(2-aminopyridin-4-yl)butoxy)-4-methoxyphenyl)-N'-(3-(5-methyl-1H-imidazol-1-yl)propyl)thiourea
Homo sapiens
pH and temperature not specified in the publication
0.0000468
N-(3-(4-(dimethylamino)butoxy)-4-methoxyphenyl)-N'-(3-(5-methyl-1H-imidazol-1-yl)propyl)thiourea
Homo sapiens
pH and temperature not specified in the publication
0.0000088
N-(3-(4-aminobutoxy)-4-methoxyphenyl)-N'-(3-(5-methyl-1H-imidazol-1-yl)propyl)thiourea
Homo sapiens
pH and temperature not specified in the publication
0.0000062
N-(3-methoxy-4-[[4-(piperidin-4-yl)phenyl]methoxy]phenyl)-N'-[3-(5-methyl-1H-imidazol-1-yl)propyl]thiourea
Homo sapiens
pH and temperature not specified in the publication
0.0000162
N-(4-((1-(2-aminoethyl)piperidin-4-yl)carbamoyl)phenyl)-N'-(3-(5-methyl-1H-imidazol-1-yl)propyl)thiourea
Homo sapiens
pH and temperature not specified in the publication
0.0000565
N-(4-(2-(((2-aminopyridin-4-yl)methyl)amino)-2-oxoethoxy)phenyl)-N'-(3-(5-methyl-1H-imidazol-1-yl)propyl)thiourea
Homo sapiens
pH and temperature not specified in the publication
0.0000079
N-(4-(2-((1-(2-aminoethyl)piperidin-4-yl)amino)-2-oxoethoxy)phenyl)-N'-(3-(5-methyl-1H-imidazol-1-yl)propyl)thiourea
Homo sapiens
pH and temperature not specified in the publication
0.0000187
N-(4-(2-(piperazin-1-yl)ethoxy)phenyl)-N'-(3-(5-methyl-1H-imidazol-1-yl)propyl)thiourea
Homo sapiens
pH and temperature not specified in the publication
0.0000114
N-(4-(2-oxo-2-(piperazin-1-yl)ethoxy)phenyl)-N'-(3-(5-methyl-1H-imidazol-1-yl)propyl)thiourea
Homo sapiens
pH and temperature not specified in the publication
0.0000129
N-(4-(2-oxo-2-(piperidin-4-ylamino)ethoxy)phenyl)-N'-(3-(5-methyl-1H-imidazol-1-yl)propyl)thiourea
Homo sapiens
pH and temperature not specified in the publication
0.0000247
N-(4-(4-(2-aminopyridin-4-yl)butoxy)phenyl)-N'-(3-(5-methyl-1H-imidazol-1-yl)propyl)thiourea
Homo sapiens
pH and temperature not specified in the publication
0.0000206
N-(4-methoxy-3-(2-(1-methylpiperidin-4-yl)ethoxy)phenyl)-N'-(3-(5-methyl-1H-imidazol-1-yl)propyl)thiourea
Homo sapiens
pH and temperature not specified in the publication
0.0000184
N-(4-methoxy-3-(2-(piperazin-1-yl)ethoxy)phenyl)-N'-(3-(5-methyl-1H-imidazol-1-yl)propyl)thiourea
Homo sapiens
pH and temperature not specified in the publication
0.0000073
N-(4-methoxy-3-(2-(piperidin-4-yl)ethoxy)phenyl)-N'-(3-(5-methyl-1H-imidazol-1-yl)propyl)thiourea
Homo sapiens
pH and temperature not specified in the publication
0.0000268
N-(4-methoxy-3-(3-(methylamino)propoxy)phenyl)-N'-(3-(5-methyl-1H-imidazol-1-yl)propyl)thiourea
Homo sapiens
pH and temperature not specified in the publication
0.0000158
N-(4-methoxy-3-(3-(piperazin-1-yl)propoxy)phenyl)-N'-(3-(5-methyl-1H-imidazol-1-yl)propyl)thiourea
Homo sapiens
pH and temperature not specified in the publication
0.0000088
N-(4-methoxy-3-(3-(piperidin-4-yl)propoxy)phenyl)-N'-(3-(5-methyl-1H-imidazol-1-yl)propyl)thiourea
Homo sapiens
pH and temperature not specified in the publication
0.000022
N-(4-methoxy-3-(4-(methylamino)butoxy)phenyl)-N'-(3-(5-methyl-1H-imidazol-1-yl)propyl)thiourea
Homo sapiens
pH and temperature not specified in the publication
0.000015
N-(4-methoxy-3-(4-(piperazin-1-yl)butoxy)phenyl)-N'-(3-(5-methyl-1H-imidazol-1-yl)propyl)thiourea
Homo sapiens
pH and temperature not specified in the publication
0.0000079
N-(4-methoxy-3-(4-(piperidin-4-yl)butoxy)phenyl)-N'-(3-(5-methyl-1H-imidazol-1-yl)propyl)thiourea
Homo sapiens
pH and temperature not specified in the publication
0.0000152
N-(4-methoxy-3-(4-(pyrimidin-2-ylamino)butoxy)phenyl)-N'-(3-(5-methyl-1H-imidazol-1-yl)propyl)thiourea
Homo sapiens
pH and temperature not specified in the publication
0.0000112
N-(E)-(4-(3-(4-(2-aminoethyl)piperazin-1-yl)-3-oxoprop-1-en-1-yl)phenyl)-N'-(3-(5-methyl-1H-imidazol-1-yl)propyl)thiourea
Homo sapiens
pH and temperature not specified in the publication
0.0000088
N-[3-(4-aminobutoxy)-4-methoxyphenyl]-N'-[3-(2-methyl-1H-imidazol-1-yl)propyl]thiourea
Homo sapiens
pH and temperature not specified in the publication
0.00045
N2-[(2S)-1-hydroxy-2-[[3-(5-methyl-1H-imidazol-1-yl)propyl]amino]-3-phenylpropyl]-L-alaninamide
Homo sapiens
pH 7.0, 37°C
0.000053
SEN-177
Homo sapiens
pH and temperature not specified in the publication
0.00017
SEN-180
Homo sapiens
pH and temperature not specified in the publication
0.0018
SEN-817
Homo sapiens
pH and temperature not specified in the publication
0.000029
N-(3,4-dimethoxyphenyl)-N'-[3-(5-methyl-1H-imidazol-1-yl)propyl]thiourea
Homo sapiens
pH 7.0, 37°C
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
additional information
-
slightly lower glutaminyl cyclase activity in cerebrospinal fluid of multiple sclerosis patients compared to controls. The presence of glutaminyl cyclase in cerebrospinal fluid can stabilize peptides from degradation by aminopeptidases
additional information
isozyme expression analysis in patients with chronic periodontitis (CP) and rheumatoid arthritis (RA), overview
additional information
isozyme expression analysis in patients with chronic periodontitis (CP) and rheumatoid arthritis (RA), overview
additional information
-
isozyme expression analysis in patients with chronic periodontitis (CP) and rheumatoid arthritis (RA), overview
additional information
enzyme QC is abundant in mammalian secretory tissue such as secretory glands or brain tissue including hippocampus and cortex
additional information
-
enzyme QC is abundant in mammalian secretory tissue such as secretory glands or brain tissue including hippocampus and cortex
additional information
isozyme expression analysis in patients with chronic periodontitis (CP) and rheumatoid arthritis (RA), overview
additional information
isozyme expression analysis in patients with chronic periodontitis (CP) and rheumatoid arthritis (RA), overview
additional information
-
isozyme expression analysis in patients with chronic periodontitis (CP) and rheumatoid arthritis (RA), overview
additional information
tissue distribution of enzyme and 5-oxoprolyl-Abeta3-40/42 peptide, detailed overview
additional information
-
tissue distribution of enzyme and 5-oxoprolyl-Abeta3-40/42 peptide, detailed overview
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
-
exclusively localized within the Golgi complex, obviously retained by the N-terminus. Retention in the Golgi complex suggests involvement in the protein maturation machinery
unlike QC, the secreted isozyme, isozyme isoQC exclusively localizes within the Golgi complex via a transmembrane domain
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
evolution
malfunction
metabolism
physiological function
evolution
malfunction
loss of the pE-modification and N-terminal charge leads to accelerated aggregation of Abeta3(pE) compared with unmodified Abeta
metabolism
the dipeptidyl-peptidase activity of meprin beta links N-truncation of Abeta with glutaminyl cyclase-catalyzed pGlu-Abeta formation
physiological function
additional information
evolution
glutaminyl cyclase (QC) and isoglutaminyl cyclase (isoQC) belong to the family of the metalloenzymes
evolution
glutaminyl cyclase (QC, glutaminyl-peptide cyclotransferase (QPCT)) and its isoenzyme isoQC (QPCTL) belong to a family of enzymes which catalyze the formation of pyroglutamate (pGlu, pE) at N-terminus of proteins by converting glutamate/glutamine to pGlu residue
malfunction
glutaminyl cyclase inhibitors alter the CD47 protein by inhibiting QPCTL function and the resulting block in pGlu-modified CD47 is nearly complete. The expansion, differentiation, cytokine production and killing capacity of human T cells is compatible with small molecule inhibition of QPCTL. But QPCTL deficiency and QPCTL inhibition enhance tumor cell control by tumor-specific antibodies
malfunction
knockout of isoQC dramatically reduces the binding of SIRPalpha to cell surface
metabolism
the activity of myeloid cells such as macrophages and neutrophils is likewise regulated by a balance between stimulatory and inhibitory signals. In particular, cell surface expression of the CD47 protein creates a 'don't eat me' signal on tumor cells by binding to SIRPalpha expressed on myeloid cells. CD47 is a broadly expressed inhibitory ligand for myeloid cells. The glutaminyl-peptide cyclotransferase-like protein (QPCTL) is a major component of the CD47-SIRPalpha checkpoint. Interference with QPCTL expression leads to a major increase in neutrophil-mediated killing of tumor cells in vivo. Diglutamate formation occurs early in the CD47 protein life cycle and fully depends on QPCTL. Synergy between blockade of CD47 diglutamate formation and tumor opsonization in tumor cell killing by macrophages and neutrophils
metabolism
transmembrane protein CD47 is highly expressed on many types of cancer cells and can directly bind to the receptor signal regulatory protein alpha (SIRPalpha), which is highly expressed on phagocytic cells. Binding of CD47 to SIRPalpha can protect cancer cells from phagocytosis by phagocytic cells and therefore functions as the major 'don't eat me' signal. Therapeutic blockade of CD47-SIRPalpha axis can efficiently promote the macrophage-mediated phagocytosis and elimination of cancer cells. Glutaminyl cyclase isoenzyme isoQC is a regulator of SIRPalpha-CD47 axis
physiological function
glutaminyl cyclase (QC) and isoglutaminyl cyclase (isoQC) catalyze the intramolecular cyclization of N-terminal L-glutamine/glutamate residues of certain proteins into diglutamic acid (pGlu). The level of CCL2 and h-isoQCmRNA in Alzheimer disease (AD) patients is significantly higher than that of healthy subjects
physiological function
glutaminyl cyclase isoenzyme isoQC is an essential regulator of CD47-SIRPalpha axis and required for efficient phagocytic cells-mediated clearance of cancer cells. N-terminal pGlu modification of proteins may protect protein from degradation by proteases or promote protein aggregation
physiological function
human glutaminyl cyclase (hQC) is an important enzyme for post-translational modification by converting the N-terminal glutaminyl and glutamyl into diglutamate (pGlu) through cyclization. The two isoforms of hQC, secretory glutaminyl cyclase (sQC) and Golgi resident glutaminyl cyclase (gQC), are involved in various pathological conditions especially in Alzheimer's disease (AD). The sQC is known to mediate the formation of diglutamate containing amyloid beta (pGlu-Abeta) peptides while gQC mediates the maturation of C-C motif chemokine ligand 2 (CCL2)
physiological function
the glutaminyl-peptide cyclotransferase-like protein (QPCTL) is a Golgi-resident enzyme that, like its secreted family member QPCT, can catalyze the cyclization of N-terminal glutamine and glutamic acid residues on target proteins into an N-terminal pyroglutamate residue (pGlu). QPCTL is a major component of the CD47-SIRPalpha checkpoint. Diglutamate formation occurs early in the CD47 protein life cycle and fully depends on QPCTL. QPCTL is critical for diglutamate formation on CD47 at the SIRPalpha binding site shortly after biosynthesis. QPCTL is a modulator of CD47-SIRPalpha binding. Genetic and pharmacological interference with QPCTL activity enhances antibody-dependent cellular phagocytosis and cellular cytotoxicity of tumor cells. Interference with QPCTL expression leads to a major increase in neutrophil-mediated killing of tumor cells in vivo
evolution
glutaminyl cyclase (QC) and isoglutaminyl cyclase (isoQC) belong to the family of the metalloenzymes
evolution
glutaminyl cyclases (QCs) belong to the class of acyl transferases. Different types of QCs are identified in bacteria, plants and animals, including mammalian tissues
physiological function
-
glutaminyl cyclase contributes to the formation of focal and diffuse diglutamate-Abeta peptide deposits in hippocampus
physiological function
amyloid-beta peptide Abeta3-40/42 is the precursor of pGlu-Abeta3-40/42 generated by glutaminyl cyclase (QC). The formation of amyloid-beta (Abeta) peptides is causally involved in the development of Alzheimer's disease (AD)
physiological function
glutaminyl cyclase (QC) and isoglutaminyl cyclase (isoQC) catalyze the intramolecular cyclization of N-terminal L-glutamine/glutamate residues of certain proteins into diglutamic acid (pGlu). The amyloid protein and the monocyte chemoattractant protein (MCP-1) also known as CCL2 that promotes a cascade of inflammation-related responses are two representative substrates. The diglutamated Abeta and CCL2 exhibit more severe neurotoxicity than normal Abeta and CCL2. The Abeta1-40/42 peptides start with an L-aspartate at the N-terminus. Under pathological conditions, the Abeta1-40/42 peptides are truncated to expose the glutamate at position 3 or 11 of the Abeta peptides. Then the N-terminal glutamate (E) will be cyclized by QC to form the pyroglutamate (pE) and the products are termed as Abeta3(pE)-40/42 or Abeta11(pE)-40/42. The pE-modification of Abeta confers unique properties, such as proteolytic resistance. pGlu-Abeta peptides exhibit enhanced toxicity compared to the unmodified Abeta peptide and promote the formation of tau tangles. In Alzheimer's disease (AD) patients and animal AD models, the level and activity of QC are significantly increased
physiological function
glutaminyl cyclase (QC) is one kind of acyltransferases, which catalyzes intramolecular cyclization of N-terminal glutamine residues to diglutamic acid (pGlu) with the concomitant liberation of ammonia. The post-translational formation of pGlu is an important process for the maturation of various bioactive neuropeptides, hormones, cytokines and for their biological activity, because the pGlu is required to protect the N termini from exopeptidase degradation and/or to develop the proper conformation. QC is abundant in mammalian secretory tissue such as secretory glands or brain tissue including hippocampus and cortex. Glutaminyl cyclase (QC) plays an important role in the initiation of the formation of neurotoxic plaques and in the pathogenesis of Alzheimer's disease (AD) due to the ability of human QC (hQC) to convert the N-terminal glutamate of beta-amyloids (Abetas) into respective pGlu-modified Abetas (pE-Abetas)
physiological function
glutaminyl cyclase activity correlates with levels of Abeta38, Abeta40 and angiogenesis mediators Flt1, Tie2, VEGFD, CAM-1 and ICAM-1 in cerebrospinal fluid of Alzheimers disease patients, core CSF diagnostic biomarkers (Abeta42, tau and p-tau) are not part of the diagnostic workup, detailed overview. Pyroglutamylation of truncated Abeta peptides, which is catalysed by enzyme glutaminyl cyclase (QC), generates pE-Abeta species with enhanced aggregation propensities and resistance to most amino-peptidases and endo-peptidases. pE-Abeta species have been identified as major constituents of Abeta plaques and reduction of pE-Abeta species is associated with improvement of cognitive tasks in animal models of Alzheimer's disease (AD). Some inflammatory or angiogenesis mediators are potential QC substrates
physiological function
glutaminyl cyclases (QCs) catalyze the intramolecular cyclization of N-terminal L-glutamine residues of peptides and proteins into pyroglutamic acid (5-oxo-prolyl, pGlu, pE) releasing ammonia, as well as the intramolecular cyclization of N-terminal glutamate residues into pyroglutamic acid. Such a type of post-translational modification stabilizes the peptides and proteins, protects them from proteolytic degradation, and can be important for their biological activity
physiological function
human glutaminyl cyclase (hQC) is an important enzyme for post-translational modification by converting the N-terminal glutaminyl and glutamyl into diglutamate (pGlu) through cyclization. The two isoforms of hQC, secretory glutaminyl cyclase (sQC) and Golgi resident glutaminyl cyclase (gQC), are involved in various pathological conditions especially in Alzheimer's disease (AD). The sQC is known to mediate the formation of diglutamate containing amyloid beta (pGlu-Abeta) peptides while gQC mediates the maturation of C-C motif chemokine ligand 2 (CCL2)
additional information
active site structure of gQC, residue W231 in gQC has adopted an outward positioning of the indole ring and is involved in hydrogen bonding with one of the neighboring amino acid P256. Substrate binding and structural analysis, detailed overview. In both QC isozymes, three acidic residues (E201, D248, and D305 in sQC, and E225, D269 and D326 in gQC) are pointed to each other and are likely to form hydrogen bonds between them. These residues play a major role in the catalysis. Catalytic reaction mechanism
additional information
active site structure of gQC, residue W231 in gQC has adopted an outward positioning of the indole ring and is involved in hydrogen bonding with one of the neighboring amino acid P256. Substrate binding and structural analysis, detailed overview. In both QC isozymes, three acidic residues (E201, D248, and D305 in sQC, and E225, D269 and D326 in gQC) are pointed to each other and are likely to form hydrogen bonds between them. These residues play a major role in the catalysis. Catalytic reaction mechanism
additional information
-
active site structure of gQC, residue W231 in gQC has adopted an outward positioning of the indole ring and is involved in hydrogen bonding with one of the neighboring amino acid P256. Substrate binding and structural analysis, detailed overview. In both QC isozymes, three acidic residues (E201, D248, and D305 in sQC, and E225, D269 and D326 in gQC) are pointed to each other and are likely to form hydrogen bonds between them. These residues play a major role in the catalysis. Catalytic reaction mechanism
additional information
two active site conformations are reported for sQC (Conf-A and Conf-B) and these are mainly associated with the orientation of W207. In Conf-A (open), the orientation of the indole ring of W207 is towards the surface of the molecule and in Conf-B (closed), the orientation is towards the Zn2+ ion. Substrate binding and structural analysis, detailed overview. In both QC isozymes, three acidic residues (E201, D248, and D305 in sQC, and E225, D269 and D326 in gQC) are pointed to each other and are likely to form hydrogen bonds between them. These residues play a major role in the catalysis. Residues C139 and C164 are not involved in catalysis. Catalytic reaction mechanism
additional information
two active site conformations are reported for sQC (Conf-A and Conf-B) and these are mainly associated with the orientation of W207. In Conf-A (open), the orientation of the indole ring of W207 is towards the surface of the molecule and in Conf-B (closed), the orientation is towards the Zn2+ ion. Substrate binding and structural analysis, detailed overview. In both QC isozymes, three acidic residues (E201, D248, and D305 in sQC, and E225, D269 and D326 in gQC) are pointed to each other and are likely to form hydrogen bonds between them. These residues play a major role in the catalysis. Residues C139 and C164 are not involved in catalysis. Catalytic reaction mechanism
additional information
-
two active site conformations are reported for sQC (Conf-A and Conf-B) and these are mainly associated with the orientation of W207. In Conf-A (open), the orientation of the indole ring of W207 is towards the surface of the molecule and in Conf-B (closed), the orientation is towards the Zn2+ ion. Substrate binding and structural analysis, detailed overview. In both QC isozymes, three acidic residues (E201, D248, and D305 in sQC, and E225, D269 and D326 in gQC) are pointed to each other and are likely to form hydrogen bonds between them. These residues play a major role in the catalysis. Residues C139 and C164 are not involved in catalysis. Catalytic reaction mechanism
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable).
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable). QPCTL_HUMAN
382
1
42924
Swiss-Prot
Mitochondrion (Reliability: 4)
PDB
SCOP
CATH
UNIPROT
ORGANISM
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
glycoprotein
glycoprotein
-
N-glycan sugar moiety is bound to Asn49 in the recombinant enzyme. Presence or absence of glycan has no apparent effect on structure, stability, or enzymatic activity of the enzyme
glycoprotein
glycosylated structures of sQC are reported in PDB which exhibit divergence in the structures especially at the loop regions constituted by F146-V153 and Q295-I303. A disulfide bridge between C139 and C164 has also been observed in the glycosylated sQC. In the glycosylated structures, the position of W207 resembles the enzyme structure Conf-B
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
analysis of several human gQC structures, i.e. PDB IDs 3PB4, 3PB6, 3PB7, 3PB8, and 3PB9, overview
sitting drop vapor diffusion method, using either 30% (w/v) PEG 200, 5% (w/v) PEG 3000, and 0.1 M MES, pH 6.0, or 50% (w/v) PEG 200, 0.2 M MgCl2, and 0.1 M cacodylate, pH 6.5
hanging drop vapor diffusion method, using 100 mM imidazole (pH 8.0), 30% (v/v) 2-methyl-2,4-pentanediol, and 11% (w/v) 4000 PEG
hanging drop vapor-diffusion method. The space group of the crystal is R32, with typical unit cells of a = b = 119 A and c = 333A, in which an asymmetric unit comprises two human glutaminyl cyclase molecules. Crystal structures of the enzyme bound to inhibitors: 1-vinylimidazole, 1-benzylimidazole and N-omega-acetylhistamine
mutant enzyme W207F, hanging drop vapor diffusion method, using 1.7 M (NH4)2SO4, 4% (v/v) dioxane, and 100 mM MES, pH 6.5, at 25°C
purified recombinant His-tagged enzyme double mutant Y115E/Y117E in complex with inhibitor SEN177 and Zn2+, vapor diffusion technique, mixing an equal volume of protein sample and precipitant solution, X-ray diffraction structure determination and analysis at 1.72 A resolution, molecular replacement with the structure PDB ID 4YU9 as template, modeling
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
E225G
site-directed mutagenesis, the mutant shows reduced enzymatic activity compared to wild-type
D248A
D305A
E201D
E201L
site-directed mutagenesis, the mutant is inactive, the side chain of L201 has oriented away from the D305 in the mutant structure
E201Q
F146A
the ratio of turnover-number to KM-value for Gln-Gln at pH 8.0 is 1.43fold lower than wild-type ratio
F325A
F325N
the mutant shows a 815fold increase in Ki of PBD150 compared to the wild type enzyme
F325Y
the mutant shows a 381fold increase in Ki of PBD150 compared to the wild type enzyme
I303A
the mutation results in a 66.3fold increase in the Ki value of PBD150 compared to the wild type enzyme
I303F
the mutation results in a 6.2fold increase in the Ki value of PBD150 compared to the wild type enzyme
I303N
the mutation results in a 112fold increase in the Ki value of PBD150 compared to the wild type enzyme
I303V
the mutation results in a 1.9fold increase in the Ki value of PBD150 compared to the wild type enzyme
I73N/C369A
-
further improvement of enzyme secretion (expressed in Pichia pastoris)
K144A
K144M
the mutant shows a 335fold increase in Ki of PBD150 compared to the wild type enzyme
K144R
the mutant shows a 237fold increase in Ki of PBD150 compared to the wild type enzyme
N49A
-
mutant enzyme is not glycosylated, kinetic properties are indistinguishable from unmutated enzyme
Q304L
the ratio of turnover-number to KM-value for Gln-Gln at pH 8.0 is 1.7fold lower than wild-type ratio
R54W
the ratio of turnover-number to KM-value for Gln-Gln at pH 8.0 is 1.4fold lower than wild-type ratio
S160G
S323A
the mutation leads to a significant decrease (0.2fold) in the Ki value of PBD150 compared to the wild type enzyme
S323T
the mutation leads to a significant decrease (0.21fold) in the Ki value of PBD150 compared to the wild type enzyme
S323V
the mutation leads to a strong decrease (0.074fold) in the Ki value of PBD150 compared to the wild type enzyme
W207F
W207L
W207Q
the mutation alters substrate conversion significantly, while the binding constants of inhibitors such as the highly potent PBD150 are minimally affected
W329A
the ratio of turnover-number to KM-value for Gln-Gln at pH 8.0 is 297fold lower than wild-type ratio
W329F
the mutation leads to a significant decrease (0.56fold) in the Ki value of PBD150 compared to the wild type enzyme
W329Y
the mutation does not affect the Ki of PBD150 compared to the wild type enzyme
Y115E/Y117E
Y299A
the mutant shows a 122fold increase in Ki of PBD150 compared to the wild type enzyme
Y299F
the mutant shows a 220fold increase in Ki of PBD150 compared to the wild type enzyme
additional information
knockout of isoQC dramatically reduces the binding of SIRPalpha to cell surface
D305A
site-directed mutagenesis, in the mutant structure, the hydrogen bonding network between the acidic residues is demolished after incorporating the Ala residue at position 305
E201D
the ratio of turnover-number to KM-value for Gln-Gln at pH 8.0 is 200fold lower than wild-type ratio
E201Q
site-directed mutagenesis, the mutant is almost inactive, the side chain of L201 has oriented away from the D305 in the mutant structure
F325A
the ratio of turnover-number to KM-value for Gln-Gln at pH 8.0 is 4.9fold lower than wild-type ratio
F325A
the mutant shows a 190fold increase in Ki of PBD150 compared to the wild type enzyme
K144A
the ratio of turnover-number to KM-value for Gln-Gln at pH 8.0 is 1.7fold lower than wild-type ratio
K144A
the mutant shows a 1.21fold increase in Ki of PBD150 compared to the wild type enzyme
S160G
site-directed mutagenesis, mutation S160G disrupts the hydrogen bond network at the active site by inducing a swing to the side chain of D248
W207F
the ratio of turnover-number to KM-value for Gln-Gln at pH 8.0 is 3.45fold lower than wild-type ratio
W207F
the mutation alters substrate conversion significantly, while the binding constants of inhibitors such as the highly potent PBD150 are minimally affected
W207F
the mutation reduces the turnover rate (kcat) of the enzyme by about 3.7fold compared to the wild type enzyme
W207L
the ratio of turnover-number to KM-value for Gln-Gln at pH 8.0 is 56fold lower than wild-type ratio
W207L
the mutation alters substrate conversion significantly, while the binding constants of inhibitors such as the highly potent PBD150 are minimally affected
Y115E/Y117E
site-directed mutagenesis, the double mutation improves the protein solubility compared to wild-type
pH STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
recombinant His-tagged wild-type enzyme from Escherichia coli strain BL21(DE3) by nickel affinity chromatography
chelating Sepharose column chromatography and butyl Sepharose column chromatography
of 6His-tagged enzyme expressed in Pichia pastoris and enzyme expressed in Escherichia coli
-
recombinant His-tagged wild-type and mutant enzymes from Escherichia coli strain BL21(DE3) by nickel affinity chromatography
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
recombinant expression of His-tagged wild-type enzyme in Escherichia coli strain BL21(DE3)
recombinant expression of wild-type and mutant isoQC in isoQC-deficient HEK-293T cells
cloned into the Escherichia coli expression vectors pMALc2 and pET19b. Expression of this cDNA in either vector results in the production of a glutaminyl cyclase fusion protein which is enzymatically active and reacts with anti-bovine glutaminyl cyclase antisera
-
expression in Pichia pastoris. In Escherichia coli only 50% of the protein does not contain a disulfide bond that is present in the enzyme expressed in Pichia pastoris
-
h-isoQC, lacking the N-terminal signal anchor and the short cytosolic tail, is expressed as a fusion protein in Escherichia coli
-
recombinant expression of His-tagged wild-type and mutant enzymes in Escherichia coli strain BL21(DE3)
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
drug development
development of small molecule inhibitors of glutaminyl cyclase and isoglutaminyl cyclase for Alzheimers disease
medicine
hQC isozymes, sQC and gQC, inhibition is considered to be an attractive strategy to prevent the formation of pGlu-Abeta and to reduce neuroinflammation and provides an opportunity for the treatment of Alzheimer disease
pharmacology
the glutaminyl-peptide cyclotransferase-like protein (QPCTL) is a target to interfere with the CD47 pathway and thereby augment antibody therapy of cancer
drug development
medicine
pharmacology
Abeta38, Abeta40 and angiogenesis mediators Flt1, Tie2, VEGFD, CAM-1 and ICAM-1 are potential pharmacodynamic markers of glutaminyl cyclase (QC) inhibition, because their levels closely correlate with QC activity in Alzheimer's disease patients. The addition of QC activity to core diagnostic cerebrospinal fluid (CSF) biomarkers may be of specific interest in clinical cases with discordant imaging and biochemical biomarker results. Core CSF diagnostic biomarkers (Abeta42, tau and p-tau) are not part of the diagnostic workup
drug development
development of hQC enzyme inhibitors, 5,6-dimethoxy-N-(3-(5-methyl-1H-imidazol-1-yl)propyl)-1Hbenzo[d]imidazol-2-amine is a potential drug for treatment of Alzheimer's disease
drug development
development of small molecule inhibitors of glutaminyl cyclase and isoglutaminyl cyclase for Alzheimers disease
drug development
the enzyme is a potential target for the development of novel anti-Alzheimer disease agents. Phenol-40 (R1-), C5-OH (R2-) and C7-OH (R3-) modified apigenin derivatives are synthesized and evaluated as another class of human QC (hQC) inhibitors
medicine
-
inhibition of glutaminyl cyclase offers a new therapeutic option for the treatment of Alzheimers disease and provides implications for other amyloidoses, such as familial Danish dementia
medicine
-
the enzyme is a pharmacological target for Alzheimers disease therapy
medicine
hQC isozymes, sQC and gQC, inhibition is considered to be an attractive strategy to prevent the formation of pGlu-Abeta and to reduce neuroinflammation and provides an opportunity for the treatment of Alzheimer disease
medicine
the development of hQC enzyme inhibitors can prevent the self-aggregation of Abeta peptides, resulting in impeding Alzheimer's disease
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Busby, W.H.; Quackenbush, G.E.; Humm, J.; Youngblood, W.W.; Kizer, J.S.
An enzyme(s) that converts glutaminyl-peptides into pyroglutamyl-peptides. Presence in pituitary, brain, adrenal medulla, and lymphocytes
J. Biol. Chem.
262
8532-8536
1987
Bos taurus, Homo sapiens, Rattus norvegicus, Sus scrofa
Song, I.; Chuang, C.Z.; Bateman, J.R.C.
Molecular cloning, sequence analysis and expression of human pituitary glutaminyl cyclase
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13
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Bateman, R.C., Jr.; Temple, J.S.; Misquitta, S.A.; Booth, R.E.
Evidence for essential histidines in human pituitary glutaminyl cyclase
Biochemistry
40
11246-11250
2001
Homo sapiens
Schilling, S.; Hoffmann, T.; Rosche, F.; Manhart, S.; Wasternack, C.; Demuth, H.U.
Heterologous expression and characterization of human glutaminyl cyclase: evidence for a disulfide bond with importance for catalytic activity
Biochemistry
41
10849-10857
2002
Homo sapiens
Schilling, S.; Manhart, S.; Hoffmann, T.; Ludwig, H.H.; Wasternack, C.; Demuth, H.U.
Substrate specificity of glutaminyl cyclases from plants and animals
Biol. Chem.
384
1583-1592
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Carica papaya, Homo sapiens
Booth, R.E.; Lovell, S.C.; Misquitta, S.A.; Bateman, R.C., Jr.
Human glutaminyl cyclase and bacterial zinc aminopeptidase share a common fold and active site
BMC Biol.
2
2
2004
Homo sapiens (Q16769), Homo sapiens
Schilling, S.; Hoffmann, T.; Manhart, S.; Hoffmann, M.; Demuth, H.U.
Glutaminyl cyclases unfold glutamyl cyclase activity under mild acid conditions
FEBS Lett.
563
191-196
2004
Carica papaya, Homo sapiens
Schilling, S.; Niestroj, A.J.; Rahfeld, J.U.; Hoffmann, T.; Wermann, M.; Zunkel, K.; Wasternack, C.; Demuth, H.U.
Identification of human glutaminyl cyclase as a metalloenzyme. Potent inhibition by imidazole derivatives and heterocyclic chelators
J. Biol. Chem.
278
49773-49779
2003
Homo sapiens (Q16769), Homo sapiens
Huang, K.F.; Liu, Y.L.; Cheng, W.J.; Ko, T.P.; Wang, A.H.
Crystal structures of human glutaminyl cyclase, an enzyme responsible for protein N-terminal pyroglutamate formation
Proc. Natl. Acad. Sci. USA
102
13117-13122
2005
Homo sapiens (Q16769), Homo sapiens
Booth, R.E.; Misquitta, S.A.; Bateman, R.C., Jr.
Human pituitary glutaminyl cyclase: expression in insect cells and dye affinity purification
Protein Expr. Purif.
32
141-146
2003
Bos taurus, Homo sapiens
Huang, K.F.; Liu, Y.L.; Wang, A.H.
Cloning, expression, characterization, and crystallization of a glutaminyl cyclase from human bone marrow: a single zinc metalloenzyme
Protein Expr. Purif.
43
65-72
2005
Homo sapiens
Cynis, H.; Schilling, S.; Bodnar, M.; Hoffmann, T.; Heiser, U.; Saido, T.C.; Demuth, H.
Inhibition of glutaminyl cyclase alters pyroglutamate formation in mammalian cells
Biochim. Biophys. Acta
1764
1618-1625
2006
Homo sapiens, Mus musculus
Buchholz, M.; Heiser, U.; Schilling, S.; Niestroj, A.J.; Zunkel, K.; Demuth, H.U.
The first potent inhibitors for human glutaminyl cyclase: synthesis and structure-activity relationship
J. Med. Chem.
49
664-677
2006
Homo sapiens
Huang, K.F.; Wang, Y.R.; Chang, E.C.; Chou, T.L.; Wang, A.H.
A conserved hydrogen-bond network in the catalytic centre of animal glutaminyl cyclases is critical for catalysis
Biochem. J.
411
181-190
2008
Homo sapiens
Cynis, H.; Scheel, E.; Saido, T.C.; Schilling, S.; Demuth, H.U.
Amyloidogenic processing of amyloid precursor protein: evidence of a pivotal role of glutaminyl cyclase in generation of pyroglutamate-modified amyloid-beta
Biochemistry
47
7405-7413
2008
Homo sapiens
Gontsarova, A.; Kaufmann, E.; Tumani, H.; Dressel, A.; Mandel, F.; Wiesmueller, K.H.; Kunert-Keil, C.; Brinkmeier, H.
Glutaminyl cyclase activity is a characteristic feature of human cerebrospinal fluid
Clin. Chim. Acta
389
152-159
2008
Homo sapiens
Cynis, H.; Rahfeld, J.U.; Stephan, A.; Kehlen, A.; Koch, B.; Wermann, M.; Demuth, H.U.; Schilling, S.
Isolation of an isoenzyme of human glutaminyl cyclase: retention in the Golgi complex suggests involvement in the protein maturation machinery
J. Mol. Biol.
379
966-980
2008
Homo sapiens
Schilling, S.; Zeitschel, U.; Hoffmann, T.; Heiser, U.; Francke, M.; Kehlen, A.; Holzer, M.; Hutter-Paier, B.; Prokesch, M.; Windisch, M.; Jagla, W.; Schlenzig, D.; Lindner, C.; Rudolph, T.; Reuter, G.; Cynis, H.; Montag, D.; Demuth, H.U.; Rossner, S.
Glutaminyl cyclase inhibition attenuates pyroglutamate Abeta and Alzheimers disease-like pathology
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1106-1111
2008
Homo sapiens
Calvaresi, M.; Garavelli, M.; Bottoni, A.
Computational evidence for the catalytic mechanism of glutaminyl cyclase. A DFT investigation
Proteins
73
527-538
2008
Homo sapiens (Q16769)
Seifert, F.; Schulz, K.; Koch, B.; Manhart, S.; Demuth, H.U.; Schilling, S.
Glutaminyl cyclases display significant catalytic proficiency for glutamyl substrates
Biochemistry
48
11831-11833
2009
Carica papaya, Homo sapiens, Mus musculus, Solanum tuberosum
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Mammalian glutaminyl cyclases and their isoenzymes have identical enzymatic characteristics
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276
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2009
Homo sapiens, Mus musculus
Buchholz, M.; Hamann, A.; Aust, S.; Brandt, W.; Boehme, L.; Hoffmann, T.; Schilling, S.; Demuth, H.U.; Heiser, U.
Inhibitors for human glutaminyl cyclase by structure based design and bioisosteric replacement
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52
7069-7080
2009
Homo sapiens (Q16769), Homo sapiens
Hartlage-Ruebsamen, M.; Morawski, M.; Waniek, A.; Jaeger, C.; Zeitschel, U.; Koch, B.; Cynis, H.; Schilling, S.; Schliebs, R.; Demuth, H.U.; Rossner, S.
Glutaminyl cyclase contributes to the formation of focal and diffuse pyroglutamate (pGlu)-Abeta deposits in hippocampus via distinct cellular mechanisms
Acta Neuropathol.
121
705-719
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Homo sapiens, Mus musculus
Ruiz-Carrillo, D.; Koch, B.; Parthier, C.; Wermann, M.; Dambe, T.; Buchholz, M.; Ludwig, H.H.; Heiser, U.; Rahfeld, J.U.; Stubbs, M.T.; Schilling, S.; Demuth, H.U.
Structures of glycosylated mammalian glutaminyl cyclases reveal conformational variability near the active center
Biochemistry
50
6280-6288
2011
Homo sapiens (Q16769), Mus musculus (Q9CYK2)
Koch, B.; Buchholz, M.; Wermann, M.; Heiser, U.; Schilling, S.; Demuth, H.U.
Probing secondary glutaminyl cyclase (QC) inhibitor interactions applying an in silico-modeling/site-directed mutagenesis approach: implications for drug development
Chem. Biol. Drug Des.
80
937-946
2012
Homo sapiens (Q16769), Mus musculus (Q9CYK2)
Huang, K.F.; Liaw, S.S.; Huang, W.L.; Chia, C.Y.; Lo, Y.C.; Chen, Y.L.; Wang, A.H.
Structures of human Golgi-resident glutaminyl cyclase and its complexes with inhibitors reveal a large loop movement upon inhibitor binding
J. Biol. Chem.
286
12439-12449
2011
Homo sapiens, Homo sapiens (Q9NXS2)
Cynis, H.; Funkelstein, L.; Toneff, T.; Mosier, C.; Ziegler, M.; Koch, B.; Demuth, H.U.; Hook, V.
Pyroglutamate-amyloid-beta and glutaminyl cyclase are colocalized with amyloid-beta in secretory vesicles and undergo activity-dependent, regulated secretion
Neurodegener. Dis.
14
85-97
2014
Bos taurus, Homo sapiens
Bridel, C.; Hoffmann, T.; Meyer, A.; Durieux, S.; Koel-Simmelink, M.A.; Orth, M.; Scheltens, P.; Lues, I.; Teunissen, C.E.
Glutaminyl cyclase activity correlates with levels of Abeta peptides and mediators of angiogenesis in cerebrospinal fluid of Alzheimers disease patients
Alzheimers Res. Ther.
9
38
2017
Homo sapiens (Q16769), Homo sapiens
Bender, P.; Egger, A.; Westermann, M.; Taudte, N.; Sculean, A.; Potempa, J.; Moeller, B.; Buchholz, M.; Eick, S.
Expression of human and Porphyromonas gingivalis glutaminyl cyclases in periodontitis and rheumatoid arthritis-A pilot study
Arch. Oral Biol.
97
223-230
2019
Porphyromonas gingivalis, Homo sapiens (Q16769), Homo sapiens (Q9NXS2), Homo sapiens
Li, M.; Dong, Y.; Yu, X.; Zou, Y.; Zheng, Y.; Bu, X.; Quan, J.; He, Z.; Wu, H.
Inhibitory effect of flavonoids on human glutaminyl cyclase
Bioorg. Med. Chem.
24
2280-2286
2016
Homo sapiens (Q16769), Homo sapiens
Ngo, V.T.H.; Hoang, V.H.; Tran, P.T.; Van Manh, N.; Ann, J.; Kim, E.; Cui, M.; Choi, S.; Lee, J.; Kim, H.; Ha, H.J.; Choi, K.; Kim, Y.H.; Lee, J.
Structure-activity relationship investigation of Phe-Arg mimetic region of human glutaminyl cyclase inhibitors
Bioorg. Med. Chem.
26
3133-3144
2018
Homo sapiens (Q16769), Homo sapiens
Wu, Z.; Weng, L.; Zhang, T.; Tian, H.; Fang, L.; Teng, H.; Zhang, W.; Gao, J.; Hao, Y.; Li, Y.; Zhou, H.; Wang, P.
Identification of glutaminyl cyclase isoenzyme isoQC as a regulator of SIRPalpha-CD47 axis
Cell Res.
29
502-505
2019
Homo sapiens (Q9NXS2)
Xu, A.; He, F.; Yu, C.; Qu, Y.; Zhang, Q.; Lv, J.; Zhang, X.; Ran, Y.; Wei, C.; Wu, J.
The development of small molecule inhibitors of glutaminyl cyclase and isoglutaminyl cyclase for Alzheimers disease
ChemistrySelect
4
10591-10600
2019
Homo sapiens (Q16769), Homo sapiens (Q9NXS2)
-
Schlenzig, D.; Cynis, H.; Hartlage-Ruebsamen, M.; Zeitschel, U.; Menge, K.; Fothe, A.; Ramsbeck, D.; Spahn, C.; Wermann, M.; Rossner, S.; Buchholz, M.; Schilling, S.; Demuth, H.U.
Dipeptidyl-peptidase activity of meprin beta links N-truncation of Abeta with glutaminyl cyclase-catalyzed pGlu-Abeta formation
J. Alzheimers Dis.
66
359-375
2018
Homo sapiens (Q16769), Homo sapiens
Pozzi, C.; Di Pisa, F.; Benvenuti, M.; Mangani, S.
The structure of the human glutaminyl cyclase-SEN177 complex indicates routes for developing new potent inhibitors as possible agents for the treatment of neurological disorders
J. Biol. Inorg. Chem.
23
1219-1226
2018
Homo sapiens (Q16769), Homo sapiens (Q9NXS2), Homo sapiens
Hielscher-Michael, S.; Griehl, C.; Buchholz, M.; Demuth, H.U.; Arnold, N.; Wessjohann, L.A.
Natural products from microalgae with potential against Alzheimers disease sulfolipids are potent glutaminyl cyclase inhibitors
Mar. Drugs
14
203
2016
Homo sapiens (Q16769)
Logtenberg, M.E.W.; Jansen, J.H.M.; Raaben, M.; Toebes, M.; Franke, K.; Brandsma, A.M.; Matlung, H.L.; Fauster, A.; Gomez-Eerland, R.; Bakker, N.A.M.; van der Schot, S.; Marijt, K.A.; Verdoes, M.; Haanen, J.B.A.G.; van den Berg, J.H.; Neefjes, J.; van den Berg, T.K.; Brummelkamp, T.R.; Leusen, J.H.W.; Scheeren, F.A.; Schumacher, T.N.
Glutaminyl cyclase is an enzymatic modifier of the CD47-SIRPalpha axis and a target for cancer immunotherapy
Nat. Med.
25
612-619
2019
Homo sapiens (Q9NXS2)
Vijayan, D.K.; Zhang, K.Y.J.
Human glutaminyl cyclase Structure, function, inhibitors and involvement in Alzheimers disease
Pharmacol. Res.
147
104342
2019
Homo sapiens (Q16769), Homo sapiens (Q9NXS2), Homo sapiens
Tran, P.; Hoang, V.; Lee, J.; Hien, T.; Tung, N.; Ngo, S.
In vitro and in silico determination of glutaminyl cyclase inhibitors
RSC Adv.
9
29619-29627
2019
Homo sapiens (Q16769)
-
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