Literature summary for 4.4.1.5 extracted from

Yuan, M.; Luo, M.; Song, Y.; Xu, Q.; Wang, X.; Cao, Y.; Bu, X.; Ren, Y.; Hu, X.
Identification of curcumin derivatives as human glyoxalase I inhibitors: A combination of biological evaluation, molecular docking, 3D-QSAR and molecular dynamics simulation studies (2011), Bioorg. Med. Chem., 19, 1189-1196.

Cloned(Commentary)

Cloned (Comment)	Organism
expression in Escherichia coli	Homo sapiens

Crystallization (Commentary)

Crystallization (Comment)	Organism
molecular docking of all inhibitors tested into crystal structure, PDB entry 1QIN. In the binding model of the three-ring curcumin derivatives, two rings lay in the opening of the active site, the third is buried into hydrophobic pocket site. 6 ns molecular dynamics simulations of compound (1E,6E)-4-(3,4-dimethoxybenzylidene)-1,7-bis(4-hydroxy-3-methoxyphenyl)hepta-1,6-diene-3,5-dione show two important hydrogen bonds: one is between hydroxyl oxygen atom of compound (1E,6E)-4-(3,4-dimethoxybenzylidene)-1,7-bis(4-hydroxy-3-methoxyphenyl)hepta-1,6-diene-3,5-dione and the nitrogen atom in residue Arg37, and one between the hydroxyl oxygen of the compound inside the hydrophobic pocket and the carbonyl oxygen of residue Met179. The original hydrogen bond disappears but a new and stable one is formed. The average distance from Zn2+ to outer carbonyl oxygen of compound (1E,6E)-4-(3,4-dimethoxybenzylidene)-1,7-bis(4-hydroxy-3-methoxyphenyl)hepta-1,6-diene-3,5-dione is about 2.095 A during 6 ns simulation. Pi-pi stacking interaction is observed between a phenyl ring of the ligand and residue Phe67	Homo sapiens

Crystallization (Comment)

Organism

molecular docking of all inhibitors tested into crystal structure, PDB entry 1QIN. In the binding model of the three-ring curcumin derivatives, two rings lay in the opening of the active site, the third is buried into hydrophobic pocket site. 6 ns molecular dynamics simulations of compound (1E,6E)-4-(3,4-dimethoxybenzylidene)-1,7-bis(4-hydroxy-3-methoxyphenyl)hepta-1,6-diene-3,5-dione show two important hydrogen bonds: one is between hydroxyl oxygen atom of compound (1E,6E)-4-(3,4-dimethoxybenzylidene)-1,7-bis(4-hydroxy-3-methoxyphenyl)hepta-1,6-diene-3,5-dione and the nitrogen atom in residue Arg37, and one between the hydroxyl oxygen of the compound inside the hydrophobic pocket and the carbonyl oxygen of residue Met179. The original hydrogen bond disappears but a new and stable one is formed. The average distance from Zn2+ to outer carbonyl oxygen of compound (1E,6E)-4-(3,4-dimethoxybenzylidene)-1,7-bis(4-hydroxy-3-methoxyphenyl)hepta-1,6-diene-3,5-dione is about 2.095 A during 6 ns simulation. Pi-pi stacking interaction is observed between a phenyl ring of the ligand and residue Phe67

Homo sapiens

Inhibitors

Inhibitors	Comment	Organism
(1E,4Z,6E)-4-(4-hydroxy-3-methoxybenzylidene)-1-(3-hydroxy-4-methoxyphenyl)-7-(4-hydroxy-3-methoxyphenyl)hepta-1,6-diene-3,5-dione	three-ring curcumin derivative, in binding model two rings lay in the opening of the active site, the third is buried into hydrophobic pocket site	Homo sapiens
(1E,6E)-4-(3,4-dimethoxybenzylidene)-1,7-bis(4-hydroxy-3-methoxyphenyl)hepta-1,6-diene-3,5-dione	three-ring curcumin derivative, in binding model two rings lay in the opening of the active site, the third is buried into hydrophobic pocket site	Homo sapiens
(1E,6E)-4-(3-fluorobenzylidene)-1,7-bis(4-hydroxy-3-methoxyphenyl)hepta-1,6-diene-3,5-dione	three-ring curcumin derivative, in binding model two rings lay in the opening of the active site, the third is buried into hydrophobic pocket site	Homo sapiens
(1E,6E)-4-(4-fluorobenzylidene)-1,7-bis(4-hydroxy-3-methoxyphenyl)hepta-1,6-diene-3,5-dione	three-ring curcumin derivative, in binding model two rings lay in the opening of the active site, the third is buried into hydrophobic pocket site	Homo sapiens
4-[(4E)-5-(3,4-dimethoxyphenyl)-2-[(2E)-3-(3,4-dimethoxyphenyl)prop-2-enoyl]-3-oxopenta-1,4-dien-1-yl]benzene-1,2-dicarbaldehyde	three-ring curcumin derivative, in binding model two rings lay in the opening of the active site, the third is buried into hydrophobic pocket site	Homo sapiens

Organism

Organism	UniProt	Comment	Textmining
Homo sapiens	-	isoform glyoxalase I	-

Source Tissue

Source Tissue	Comment	Organism	Textmining
UAMS-32 cell	-	Homo sapiens	-

Ki Value [mM]

Ki Value [mM]	Ki Value maximum [mM]	Inhibitor	Comment	Organism
0.0026	-	(1E,6E)-4-(3-fluorobenzylidene)-1,7-bis(4-hydroxy-3-methoxyphenyl)hepta-1,6-diene-3,5-dione	pH 7.1, 30°C	Homo sapiens
0.0032	-	(1E,6E)-4-(4-fluorobenzylidene)-1,7-bis(4-hydroxy-3-methoxyphenyl)hepta-1,6-diene-3,5-dione	pH 7.1, 30°C	Homo sapiens
0.0036	-	4-[(4E)-5-(3,4-dimethoxyphenyl)-2-[(2E)-3-(3,4-dimethoxyphenyl)prop-2-enoyl]-3-oxopenta-1,4-dien-1-yl]benzene-1,2-dicarbaldehyde	pH 7.1, 30°C	Homo sapiens
0.0036	-	(1E,4Z,6E)-4-(4-hydroxy-3-methoxybenzylidene)-1-(3-hydroxy-4-methoxyphenyl)-7-(4-hydroxy-3-methoxyphenyl)hepta-1,6-diene-3,5-dione	pH 7.1, 30°C	Homo sapiens
0.0046	-	(1E,6E)-4-(3,4-dimethoxybenzylidene)-1,7-bis(4-hydroxy-3-methoxyphenyl)hepta-1,6-diene-3,5-dione	pH 7.1, 30°C	Homo sapiens