Application | Comment | Organism |
---|---|---|
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 | Homo sapiens |
Cloned (Comment) | Organism |
---|---|
recombinant expression of wild-type and mutant isozyme sQC | Homo sapiens |
Crystallization (Comment) | Organism |
---|---|
analysis of 23 human sQC structures, diverse PDB IDs, overview | Homo sapiens |
analysis of several human gQC structures, i.e. PDB IDs 3PB4, 3PB6, 3PB7, 3PB8, and 3PB9, overview | Homo sapiens |
Protein Variants | Comment | Organism |
---|---|---|
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 | Homo sapiens |
E201L | site-directed mutagenesis, the mutant is inactive, the side chain of L201 has oriented away from the D305 in the mutant structure | Homo sapiens |
E201Q | site-directed mutagenesis, the mutant is almost inactive, the side chain of L201 has oriented away from the D305 in the mutant structure | Homo sapiens |
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 | Homo sapiens |
Y115E/Y117E | site-directed mutagenesis, the double mutation improves the protein solubility compared to wild-type | Homo sapiens |
Inhibitors | Comment | Organism | Structure |
---|---|---|---|
(E)-N1-(5-methyl-1H-imidazol-1-yl)-2-nitro-N'1-[4-(trifluoromethyl)phenyl]ethene-1,1-diamine | - |
Homo sapiens | |
1-(3,4-dimethoxyphenyl)-N-(1H-imidazol-1-yl)cyclopropane-1-carbothioamide | - |
Homo sapiens | |
1-(3,4-dimethoxyphenyl)-N-(4-methyl-1H-imidazol-1-yl)cyclopropane-1-carbothioamide | - |
Homo sapiens | |
1-(3,4-dimethoxyphenyl)-N-(5-methyl-1H-imidazol-1-yl)cyclopropane-1-carbothioamide | - |
Homo sapiens | |
2-(4-ethoxyphenyl)-5,7-dihydroxy-4H-1-benzopyran-4-one | - |
Homo sapiens | |
3-(5-methyl-1H-imidazol-1-yl)-6-phenyl-2-sulfanylidene-2,3-dihydrothieno[2,3-d]pyrimidin-4(1H)-one | - |
Homo sapiens | |
5,7-dihydroxy-2-(5-methylthiophen-2-yl)-4H-1-benzopyran-4-one | - |
Homo sapiens | |
5,7-dihydroxy-2-(thiophen-2-yl)-4H-1-benzopyran-4-one | - |
Homo sapiens | |
additional information | structure-function analysis of enzyme inhibitors, overview; 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 | Homo sapiens | |
N''-cyano-N-(5-methyl-1H-imidazol-1-yl)-N'-(3,4,5-trimethoxyphenyl)guanidine | - |
Homo sapiens | |
N-(3,4-dimethoxyphenyl)-N'-(4-methyl-1H-imidazol-1-yl)thiourea | - |
Homo sapiens | |
N-(3,4-dimethoxyphenyl)-N'-(5-methyl-1H-imidazol-1-yl)thiourea | - |
Homo sapiens | |
N-(3,4-dimethoxyphenyl)-N'-1H-imidazol-1-ylthiourea | - |
Homo sapiens | |
N-(3,4-dimethoxyphenyl)-N'-[3-(1H-imidazol-1-yl)propyl]thiourea | - |
Homo sapiens | |
N-(4'-fluoro[1,1'-biphenyl]-2-yl)-4-methyl-1H-imidazol-1-amine | - |
Homo sapiens | |
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 | - |
Homo sapiens | |
N-[3-(1H-imidazol-1-yl)propyl]-N'-phenylthiourea | - |
Homo sapiens | |
N-[3-methoxy-4-[(piperidin-4-yl)methoxy]phenyl]-N'-(5-methyl-1H-imidazol-1-yl)thiourea | - |
Homo sapiens | |
N-[4-(2-aminoethoxy)-3-methoxyphenyl]-N'-(5-methyl-1H-imidazol-1-yl)thiourea | - |
Homo sapiens | |
N-[4-(3-aminopropoxy)-3-methoxyphenyl]-N'-(5-methyl-1H-imidazol-1-yl)thiourea | - |
Homo sapiens | |
N-[4-(4-aminobutoxy)-3-methoxyphenyl]-N'-(5-methyl-1H-imidazol-1-yl)thiourea | - |
Homo sapiens | |
N-[4-[3-(2-aminopyridin-4-yl)propoxy]-3-methoxyphenyl]-N'-(5-methyl-1H-imidazol-1-yl)thiourea | - |
Homo sapiens | |
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 | Homo sapiens | |
SEN-180 | - |
Homo sapiens | |
SEN-817 | - |
Homo sapiens | |
SEN177 | - |
Homo sapiens | |
Sen180 | - |
Homo sapiens | |
Sen817 | - |
Homo sapiens |
Localization | Comment | Organism | GeneOntology No. | Textmining |
---|---|---|---|---|
extracellular | - |
Homo sapiens | - |
- |
Golgi apparatus | - |
Homo sapiens | 5794 | - |
Metals/Ions | Comment | Organism | Structure |
---|---|---|---|
Zn2+ | active site bound and involved in catalysis | Homo sapiens | |
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 | Homo sapiens |
Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
---|---|---|---|---|---|---|
L-glutaminyl-peptide | Homo sapiens | - |
5-oxoprolyl-peptide + NH3 | - |
? |
Organism | UniProt | Comment | Textmining |
---|---|---|---|
Homo sapiens | Q16769 | - |
- |
Homo sapiens | Q9NXS2 | - |
- |
Posttranslational Modification | Comment | Organism |
---|---|---|
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 | Homo sapiens |
Source Tissue | Comment | Organism | Textmining |
---|---|---|---|
brain | - |
Homo sapiens | - |
Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
---|---|---|---|---|---|---|
L-glutaminyl-peptide | - |
Homo sapiens | 5-oxoprolyl-peptide + NH3 | - |
? |
Synonyms | Comment | Organism |
---|---|---|
glutaminyl cyclase | - |
Homo sapiens |
Golgi resident glutaminyl cyclase | - |
Homo sapiens |
gQC | - |
Homo sapiens |
hQC | - |
Homo sapiens |
secretory glutaminyl cyclase | - |
Homo sapiens |
sQC | - |
Homo sapiens |
IC50 Value | IC50 Value Maximum | Comment | Organism | Inhibitor | Structure |
---|---|---|---|---|---|
0.000013 | - |
pH and temperature not specified in the publication | Homo sapiens | SEN177 | |
0.000053 | - |
pH and temperature not specified in the publication | Homo sapiens | SEN-177 | |
0.000058 | - |
pH and temperature not specified in the publication | Homo sapiens | Sen180 | |
0.00017 | - |
pH and temperature not specified in the publication | Homo sapiens | SEN-180 | |
0.0018 | - |
pH and temperature not specified in the publication | Homo sapiens | SEN-817 | |
0.0023 | - |
pH and temperature not specified in the publication | Homo sapiens | Sen817 |
General Information | Comment | Organism |
---|---|---|
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 | Homo sapiens |
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 | Homo sapiens |
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) | Homo sapiens |