Activating Compound | Comment | Organism | Structure |
---|---|---|---|
4-methylimidazole | enzyme bound structure, PDB ID 4HEY | Homo sapiens | |
CAA12i | carbonic anhydrase activator 12i, enzyme binding structure determination and analysis, the location of the imidazole moiety in both conformations of CAA12i flips between two small hydrophobic cavities flanking Phe131. This movement may be analogous to the movement observed with His64 as it performs its proton-shuttling function. Conformation A may represent the in conformation of His64, as this position forms an extension of the proton wire network. In conformation B, the CAA12i tail moiety is extended away from the proton network, and this may be analogous to the out conformation of His64. Overall, the crystal structure of this CAA12i ligand indicates possible transient motion that may be essential to its activation function | Homo sapiens | |
histamine | enzyme bound structure, PDB ID 1AVN | Homo sapiens | |
histidine | enzyme bound structure, PDB ID 2ABE | Homo sapiens | |
additional information | proposed mechanism of CA enzyme activation by the compounds | Homo sapiens | |
phenylalanine | enzyme bound structure, PDB ID 2FMG | Homo sapiens |
Cloned (Comment) | Organism |
---|---|
gene CA2, recombinant expression of the enzyme in Escherichia coli strain BL21(DE3) | Homo sapiens |
Crystallization (Comment) | Organism |
---|---|
purified recombinant human CA II in complex with imidazole-based activator CAA12i, hanging drop vapor diffusion method, mixing of 10 mg/ml protein and 0.2 mM ligand in 50 mM Tris-HCl, pH 7.8, with reservoir solution, containing 50 mM Tris HCl and 1.3 M sodium citrate, pH 7.4, in a 1:1 ratio, 23°C, 7 days without agitation, X-ray diffraction structure determination and analysis at 1.6 A resolution | Homo sapiens |
Inhibitors | Comment | Organism | Structure |
---|---|---|---|
1-[2-(1H-imidazol-5-yl)ethyl]-4-methyl-2,6-di(propan-2-yl)pyridin-1-ium hexafluorophosphate | - |
Homo sapiens | |
N'',N'''-bis[(E)-(2,3,4-trihydroxyphenyl)methylidene]carbonic dihydrazide | - |
Homo sapiens | |
N'',N'''-bis[(E)-(2,3-dihydroxyphenyl)methylidene]carbonic dihydrazide | - |
Homo sapiens | |
N'',N'''-bis[(E)-(2,4,6-trihydroxyphenyl)methylidene]carbonic dihydrazide | - |
Homo sapiens | |
N'',N'''-Bis[(E)-(2,4-dichlorophenyl)methylidene]carbonic dihydrazide | - |
Homo sapiens | |
N'',N'''-bis[(E)-(2,5-dihydroxyphenyl)methylidene]carbonic dihydrazide | - |
Homo sapiens | |
N'',N'''-bis[(E)-(2,6-dichlorophenyl)methylidene]carbonic dihydrazide | mixed-type inhibition | Homo sapiens | |
N'',N'''-bis[(E)-(2-bromophenyl)methylidene]carbonic dihydrazide | - |
Homo sapiens | |
N'',N'''-bis[(E)-(2-chloro-5-nitrophenyl)methylidene]carbonic dihydrazide | mixed-type inhibition | Homo sapiens | |
N'',N'''-bis[(E)-(2-chlorophenyl)methylidene]carbonic dihydrazide | mixed-type inhibition | Homo sapiens | |
N'',N'''-bis[(E)-(2-fluorophenyl)methylidene]carbonic dihydrazide | - |
Homo sapiens | |
N'',N'''-bis[(E)-(2-hydroxy-3-methoxyphenyl)methylidene]carbonic dihydrazide | - |
Homo sapiens | |
N'',N'''-bis[(E)-(2-hydroxy-5-methoxyphenyl)methylidene]carbonic dihydrazide | - |
Homo sapiens | |
N'',N'''-bis[(E)-(2-hydroxyphenyl)methylidene]carbonic dihydrazide | - |
Homo sapiens | |
N'',N'''-bis[(E)-(2-methoxyphenyl)methylidene]carbonic dihydrazide | - |
Homo sapiens | |
N'',N'''-bis[(E)-(2-nitrophenyl)methylidene]carbonic dihydrazide | mixed-type inhibition | Homo sapiens | |
N'',N'''-bis[(E)-(3,4-dimethoxyphenyl)methylidene]carbonic dihydrazide | - |
Homo sapiens | |
N'',N'''-bis[(E)-(3-ethoxy-2-hydroxyphenyl)methylidene]carbonic dihydrazide | - |
Homo sapiens | |
N'',N'''-bis[(E)-(3-hydroxyphenyl)methylidene]carbonic dihydrazide | - |
Homo sapiens | |
N'',N'''-bis[(E)-(3-methoxyphenyl)methylidene]carbonic dihydrazide | - |
Homo sapiens | |
N'',N'''-bis[(E)-(4-bromophenyl)methylidene]carbonic dihydrazide | mixed-type inhibition | Homo sapiens | |
N'',N'''-bis[(E)-(4-chlorophenyl)methylidene]carbonic dihydrazide | - |
Homo sapiens | |
N'',N'''-bis[(E)-(4-fluorophenyl)methylidene]carbonic dihydrazide | - |
Homo sapiens | |
N'',N'''-bis[(E)-(4-hydroxyphenyl)methylidene]carbonic dihydrazide | - |
Homo sapiens | |
N'',N'''-bis[(E)-(4-methoxyphenyl)methylidene]carbonic dihydrazide | - |
Homo sapiens | |
N'',N'''-bis[(E)-(4-nitrophenyl)methylidene]carbonic dihydrazide | mixed-type inhibition | Homo sapiens | |
N'',N'''-bis[(E)-(5-bromo-2-hydroxyphenyl)methylidene]carbonic dihydrazide | - |
Homo sapiens | |
N'',N'''-bis[(E)-phenylmethylidene]carbonic dihydrazide | - |
Homo sapiens |
Metals/Ions | Comment | Organism | Structure |
---|---|---|---|
Zn2+ | required, metalloenzyme | Homo sapiens |
Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
---|---|---|---|---|---|---|
H2CO3 | Homo sapiens | - |
CO2 + H2O | - |
r |
Organism | UniProt | Comment | Textmining |
---|---|---|---|
Homo sapiens | P00918 | - |
- |
Purification (Comment) | Organism |
---|---|
recombinant enzyme from Escherichia coli strain BL21(DE3) by 4-aminomethylbenzenesulfonamide agarose affinity chromatography and ultrafiltration | Homo sapiens |
Source Tissue | Comment | Organism | Textmining |
---|---|---|---|
additional information | isozyme human CA II is ubiquitously-expressed | Homo sapiens | - |
neuron | - |
Homo sapiens | - |
Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
---|---|---|---|---|---|---|
H2CO3 | - |
Homo sapiens | CO2 + H2O | - |
r |
Synonyms | Comment | Organism |
---|---|---|
alpha-CA | - |
Homo sapiens |
CA II | - |
Homo sapiens |
CA2 | - |
Homo sapiens |
carbonic anhydrase 2 | - |
Homo sapiens |
carbonic anhydrase II | - |
Homo sapiens |
Ki Value [mM] | Ki Value maximum [mM] | Inhibitor | Comment | Organism | Structure |
---|---|---|---|---|---|
0.00178 | - |
N'',N'''-bis[(E)-(2,6-dichlorophenyl)methylidene]carbonic dihydrazide | pH 7.4, 25°C | Homo sapiens | |
0.00181 | - |
N'',N'''-bis[(E)-(2-nitrophenyl)methylidene]carbonic dihydrazide | pH 7.4, 25°C | Homo sapiens | |
0.00235 | - |
N'',N'''-bis[(E)-(4-nitrophenyl)methylidene]carbonic dihydrazide | pH 7.4, 25°C | Homo sapiens | |
0.00252 | - |
N'',N'''-bis[(E)-(4-bromophenyl)methylidene]carbonic dihydrazide | pH 7.4, 25°C | Homo sapiens | |
0.00358 | - |
N'',N'''-bis[(E)-(2-chloro-5-nitrophenyl)methylidene]carbonic dihydrazide | pH 7.4, 25°C | Homo sapiens | |
0.00412 | - |
N'',N'''-bis[(E)-(2-chlorophenyl)methylidene]carbonic dihydrazide | pH 7.4, 25°C | Homo sapiens |
IC50 Value | IC50 Value Maximum | Comment | Organism | Inhibitor | Structure |
---|---|---|---|---|---|
0.00133 | - |
pH 7.4, 25°C | Homo sapiens | N'',N'''-bis[(E)-(4-nitrophenyl)methylidene]carbonic dihydrazide | |
0.00137 | - |
pH 7.4, 25°C | Homo sapiens | N'',N'''-bis[(E)-(2-chloro-5-nitrophenyl)methylidene]carbonic dihydrazide | |
0.00146 | - |
pH 7.4, 25°C | Homo sapiens | N'',N'''-bis[(E)-(2,6-dichlorophenyl)methylidene]carbonic dihydrazide | |
0.00185 | - |
pH 7.4, 25°C | Homo sapiens | N'',N'''-bis[(E)-(2-nitrophenyl)methylidene]carbonic dihydrazide | |
0.00232 | - |
pH 7.4, 25°C | Homo sapiens | N'',N'''-bis[(E)-(4-bromophenyl)methylidene]carbonic dihydrazide | |
0.00233 | - |
pH 7.4, 25°C | Homo sapiens | N'',N'''-bis[(E)-(2-chlorophenyl)methylidene]carbonic dihydrazide | |
0.00267 | - |
pH 7.4, 25°C | Homo sapiens | N'',N'''-Bis[(E)-(2,4-dichlorophenyl)methylidene]carbonic dihydrazide | |
0.00396 | - |
pH 7.4, 25°C | Homo sapiens | N'',N'''-bis[(E)-(2-bromophenyl)methylidene]carbonic dihydrazide |
General Information | Comment | Organism |
---|---|---|
physiological function | carbonic anhydrase (CA) plays a key role in neuronal signaling, providing bicarbonate and proton ions for GABAergic and glutamatergic neuronal function. Activation of CA isoforms expressed in neurons have been shown to have implications in the prognosis of Alzheimer's disease and dementia, while inhibitors of CAs are clinically used in the treatment of epilepsy, emphasizing the importance of this family of enzymes in both disease and normal neuronal function | Homo sapiens |