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Catalytic Site Atlas

CSA LITERATURE entry for 1ca2

E.C. namecarbonate dehydratase
SpeciesHomo sapiens (Human)
E.C. Number (IntEnz)
CSA Homologues of 1ca2There are 321 Homologs
CSA Entries With UniProtID P00918
CSA Entries With EC Number
PDBe Entry 1ca2
PDBSum Entry 1ca2
MACiE Entry M0216

Literature Report

IntroductionCarbonic acid anhydrase is able to catalyse the conversion of carbon dioxide to carbonic acid and vice versa. This is important in metabolism because it enables the creation of carbonic acid, a very important buffer in the blood which has a vital role in human physiology.
MechansimThe reaction proceeds in two steps. First, an OH- bound to the Zinc ion attacks the carbon dioxide substrate forming bicarbonate and leaving a water at the Zinc ion. Polarisation of the C=O bond of carbon dioxide is achieved by Thr 199. Following this step, the OH- is regenerated by deprotonation of a water molecule by His 64, with Zinc acting to increase the polarity of the OH bond by withdrawing electrons from the oxygen atom.

Catalytic Sites for 1ca2

Annotated By Reference To The Literature - Site 2 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
ThrA199macie:sideChainThe interaction between the Thr199 and hydroxide serve to enhance the nucleophilicity of the hydroxide and help orient the substrate (CO2) in the active site.
HisA6464macie:sideChainIs able to deprotonate a water molecule allowing the formation of the catalytic nucleophile OH-.
GluA106macie:sideChainHydrogen bonds to the hydroxyl of Thr199, activiating it

Literature References

Eriksson AE
Refined structure of human carbonic anhydrase II at 2.0 A resolution.
Proteins 1988 4 274-282
PubMed: 3151019
Fisher Z
Structural and kinetic characterization of active-site histidine as a proton shuttle in catalysis by human carbonic anhydrase II.
Biochemistry 2005 44 1097-1105
PubMed: 15667203
Role of histidine 64 in the catalytic mechanism of human carbonic anhydrase II studied with a site-specific mutant.
Biochemistry 1989 28 7913-7918
PubMed: 2514797
Huang S
Crystal structure of carbonic anhydrase from Neisseria gonorrhoeae and its complex with the inhibitor acetazolamide.
J Mol Biol 1998 283 301-310
PubMed: 9761692
Supuran CT
Carbonic anhydrase inhibitors.
Med Res Rev 2003 23 146-189
PubMed: 12500287
Lindskog S.
Structure and mechanism of carbonic anhydrase.
Pharmacol Ther 1997 74 1-20
PubMed: 9336012