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Literature summary extracted from

  • Bhatt, A.; Mondal, U.K.; Supuran, C.T.; Ilies, M.A.; McKenna, R.
    Crystal structure of carbonic anhydrase II in complex with an activating ligand implications in neuronal function (2018), Mol. Neurobiol., 55, 7431-7437 .
    View publication on PubMed

Activating Compound

EC Number Activating Compound Comment Organism Structure
4.2.1.1 4-methylimidazole enzyme bound structure, PDB ID 4HEY Homo sapiens
4.2.1.1 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
4.2.1.1 histamine enzyme bound structure, PDB ID 1AVN Homo sapiens
4.2.1.1 histidine enzyme bound structure, PDB ID 2ABE Homo sapiens
4.2.1.1 additional information proposed mechanism of CA enzyme activation by the compounds Homo sapiens
4.2.1.1 phenylalanine enzyme bound structure, PDB ID 2FMG Homo sapiens

Cloned(Commentary)

EC Number Cloned (Comment) Organism
4.2.1.1 gene CA2, recombinant expression of the enzyme in Escherichia coli strain BL21(DE3) Homo sapiens

Crystallization (Commentary)

EC Number Crystallization (Comment) Organism
4.2.1.1 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

EC Number Inhibitors Comment Organism Structure
4.2.1.1 1-[2-(1H-imidazol-5-yl)ethyl]-4-methyl-2,6-di(propan-2-yl)pyridin-1-ium hexafluorophosphate
-
 Homo sapiens
4.2.1.1 N'',N'''-bis[(E)-(2,3,4-trihydroxyphenyl)methylidene]carbonic dihydrazide
-
 Homo sapiens
4.2.1.1 N'',N'''-bis[(E)-(2,3-dihydroxyphenyl)methylidene]carbonic dihydrazide
-
 Homo sapiens
4.2.1.1 N'',N'''-bis[(E)-(2,4,6-trihydroxyphenyl)methylidene]carbonic dihydrazide
-
 Homo sapiens
4.2.1.1 N'',N'''-Bis[(E)-(2,4-dichlorophenyl)methylidene]carbonic dihydrazide
-
 Homo sapiens
4.2.1.1 N'',N'''-bis[(E)-(2,5-dihydroxyphenyl)methylidene]carbonic dihydrazide
-
 Homo sapiens
4.2.1.1 N'',N'''-bis[(E)-(2,6-dichlorophenyl)methylidene]carbonic dihydrazide mixed-type inhibition Homo sapiens
4.2.1.1 N'',N'''-bis[(E)-(2-bromophenyl)methylidene]carbonic dihydrazide
-
 Homo sapiens
4.2.1.1 N'',N'''-bis[(E)-(2-chloro-5-nitrophenyl)methylidene]carbonic dihydrazide mixed-type inhibition Homo sapiens
4.2.1.1 N'',N'''-bis[(E)-(2-chlorophenyl)methylidene]carbonic dihydrazide mixed-type inhibition Homo sapiens
4.2.1.1 N'',N'''-bis[(E)-(2-fluorophenyl)methylidene]carbonic dihydrazide
-
 Homo sapiens
4.2.1.1 N'',N'''-bis[(E)-(2-hydroxy-3-methoxyphenyl)methylidene]carbonic dihydrazide
-
 Homo sapiens
4.2.1.1 N'',N'''-bis[(E)-(2-hydroxy-5-methoxyphenyl)methylidene]carbonic dihydrazide
-
 Homo sapiens
4.2.1.1 N'',N'''-bis[(E)-(2-hydroxyphenyl)methylidene]carbonic dihydrazide
-
 Homo sapiens
4.2.1.1 N'',N'''-bis[(E)-(2-methoxyphenyl)methylidene]carbonic dihydrazide
-
 Homo sapiens
4.2.1.1 N'',N'''-bis[(E)-(2-nitrophenyl)methylidene]carbonic dihydrazide mixed-type inhibition Homo sapiens
4.2.1.1 N'',N'''-bis[(E)-(3,4-dimethoxyphenyl)methylidene]carbonic dihydrazide
-
 Homo sapiens
4.2.1.1 N'',N'''-bis[(E)-(3-ethoxy-2-hydroxyphenyl)methylidene]carbonic dihydrazide
-
 Homo sapiens
4.2.1.1 N'',N'''-bis[(E)-(3-hydroxyphenyl)methylidene]carbonic dihydrazide
-
 Homo sapiens
4.2.1.1 N'',N'''-bis[(E)-(3-methoxyphenyl)methylidene]carbonic dihydrazide
-
 Homo sapiens
4.2.1.1 N'',N'''-bis[(E)-(4-bromophenyl)methylidene]carbonic dihydrazide mixed-type inhibition Homo sapiens
4.2.1.1 N'',N'''-bis[(E)-(4-chlorophenyl)methylidene]carbonic dihydrazide
-
 Homo sapiens
4.2.1.1 N'',N'''-bis[(E)-(4-fluorophenyl)methylidene]carbonic dihydrazide
-
 Homo sapiens
4.2.1.1 N'',N'''-bis[(E)-(4-hydroxyphenyl)methylidene]carbonic dihydrazide
-
 Homo sapiens
4.2.1.1 N'',N'''-bis[(E)-(4-methoxyphenyl)methylidene]carbonic dihydrazide
-
 Homo sapiens
4.2.1.1 N'',N'''-bis[(E)-(4-nitrophenyl)methylidene]carbonic dihydrazide mixed-type inhibition Homo sapiens
4.2.1.1 N'',N'''-bis[(E)-(5-bromo-2-hydroxyphenyl)methylidene]carbonic dihydrazide
-
 Homo sapiens
4.2.1.1 N'',N'''-bis[(E)-phenylmethylidene]carbonic dihydrazide
-
 Homo sapiens

Metals/Ions

EC Number Metals/Ions Comment Organism Structure
4.2.1.1 Zn2+ required, metalloenzyme Homo sapiens

Natural Substrates/ Products (Substrates)

EC Number Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
4.2.1.1 H2CO3 Homo sapiens
-
 CO2 + H2O
-
 r

Organism

EC Number Organism UniProt Comment Textmining
4.2.1.1 Homo sapiens P00918
-
-

Purification (Commentary)

EC Number Purification (Comment) Organism
4.2.1.1 recombinant enzyme from Escherichia coli strain BL21(DE3) by 4-aminomethylbenzenesulfonamide agarose affinity chromatography and ultrafiltration Homo sapiens

Source Tissue

EC Number Source Tissue Comment Organism Textmining
4.2.1.1 additional information isozyme human CA II is ubiquitously-expressed Homo sapiens
-
4.2.1.1 neuron
-
 Homo sapiens
-

Substrates and Products (Substrate)

EC Number Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
4.2.1.1 H2CO3
-
 Homo sapiens CO2 + H2O
-
 r

Synonyms

EC Number Synonyms Comment Organism
4.2.1.1 alpha-CA
-
 Homo sapiens
4.2.1.1 CA II
-
 Homo sapiens
4.2.1.1 CA2
-
 Homo sapiens
4.2.1.1 carbonic anhydrase 2
-
 Homo sapiens
4.2.1.1 carbonic anhydrase II
-
 Homo sapiens

Ki Value [mM]

EC Number Ki Value [mM] Ki Value maximum [mM] Inhibitor Comment Organism Structure
4.2.1.1 0.00178
-
 N'',N'''-bis[(E)-(2,6-dichlorophenyl)methylidene]carbonic dihydrazide pH 7.4, 25°C Homo sapiens
4.2.1.1 0.00181
-
 N'',N'''-bis[(E)-(2-nitrophenyl)methylidene]carbonic dihydrazide pH 7.4, 25°C Homo sapiens
4.2.1.1 0.00235
-
 N'',N'''-bis[(E)-(4-nitrophenyl)methylidene]carbonic dihydrazide pH 7.4, 25°C Homo sapiens
4.2.1.1 0.00252
-
 N'',N'''-bis[(E)-(4-bromophenyl)methylidene]carbonic dihydrazide pH 7.4, 25°C Homo sapiens
4.2.1.1 0.00358
-
 N'',N'''-bis[(E)-(2-chloro-5-nitrophenyl)methylidene]carbonic dihydrazide pH 7.4, 25°C Homo sapiens
4.2.1.1 0.00412
-
 N'',N'''-bis[(E)-(2-chlorophenyl)methylidene]carbonic dihydrazide pH 7.4, 25°C Homo sapiens

IC50 Value

EC Number IC50 Value IC50 Value Maximum Comment Organism Inhibitor Structure
4.2.1.1 0.00133
-
 pH 7.4, 25°C Homo sapiens N'',N'''-bis[(E)-(4-nitrophenyl)methylidene]carbonic dihydrazide
4.2.1.1 0.00137
-
 pH 7.4, 25°C Homo sapiens N'',N'''-bis[(E)-(2-chloro-5-nitrophenyl)methylidene]carbonic dihydrazide
4.2.1.1 0.00146
-
 pH 7.4, 25°C Homo sapiens N'',N'''-bis[(E)-(2,6-dichlorophenyl)methylidene]carbonic dihydrazide
4.2.1.1 0.00185
-
 pH 7.4, 25°C Homo sapiens N'',N'''-bis[(E)-(2-nitrophenyl)methylidene]carbonic dihydrazide
4.2.1.1 0.00232
-
 pH 7.4, 25°C Homo sapiens N'',N'''-bis[(E)-(4-bromophenyl)methylidene]carbonic dihydrazide
4.2.1.1 0.00233
-
 pH 7.4, 25°C Homo sapiens N'',N'''-bis[(E)-(2-chlorophenyl)methylidene]carbonic dihydrazide
4.2.1.1 0.00267
-
 pH 7.4, 25°C Homo sapiens N'',N'''-Bis[(E)-(2,4-dichlorophenyl)methylidene]carbonic dihydrazide
4.2.1.1 0.00396
-
 pH 7.4, 25°C Homo sapiens N'',N'''-bis[(E)-(2-bromophenyl)methylidene]carbonic dihydrazide

General Information

EC Number General Information Comment Organism
4.2.1.1 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