DB code: D00474

RLCP classification 4.15.898510.455 : Addition
CATH domain 3.40.1050.10 : Beta-carbonic Anhydrase; Chain A Catalytic domain
3.40.1050.10 : Beta-carbonic Anhydrase; Chain A Catalytic domain
E.C. 4.2.1.1
CSA
M-CSA
MACiE

CATH domain Related DB codes (homologues)
3.40.1050.10 : Beta-carbonic Anhydrase; Chain A S00521 S00424

Uniprot Enzyme Name
UniprotKB Protein name Synonyms Pfam
Q43060 Carbonic anhydrase
EC 4.2.1.1
PF00484 (Pro_CA)
[Graphical View]

KEGG enzyme name
carbonate dehydratase
carbonic anhydrase
anhydrase
carbonate anhydrase
carbonic acid anhydrase
carboxyanhydrase
carbonic anhydrase A
carbonate hydro-lyase

UniprotKB: Accession Number Entry name Activity Subunit Subcellular location Cofactor
Q43060 Q43060_PORCR H(2)CO(3) = CO(2) + H(2)O.

KEGG Pathways
Map code Pathways E.C.
MAP00910 Nitrogen metabolism

Compound table
Cofactors Substrates Products Intermediates
KEGG-id C00038 C00011 C00001 C01353
E.C.
Compound Zinc CO2 H2O Carbonic acid
Type heavy metal others H2O carboxyl group
ChEBI 29105
16526
15377
28976
PubChem 32051
280
22247451
962
22639876
3614646
767
1ddzA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:_ZN Unbound Unbound
1ddzB01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:_ZN Unbound Unbound
1ddzA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:_ZN Unbound Unbound
1ddzB02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:_ZN Unbound Unbound

Reference for Active-site residues
resource references E.C.
literature [7]

Active-site residues
PDB Catalytic residues Cofactor-binding residues Modified residues Main-chain involved in catalysis Comment
1ddzA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain GLN 394;ASP 405;TYR 444 CYS 403;ASP 405;HIS 459;CYS 462(Zinc binding)
1ddzB01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain GLN 394;ASP 405;TYR 444 CYS 403;ASP 405;HIS 459;CYS 462(Zinc binding)
1ddzA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain GLN 140;ASP 151;TYR 190 CYS 149;ASP 151;HIS 205;CYS 208(Zinc binding)
1ddzB02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain GLN 140;ASP 151;TYR 190 CYS 149;ASP 151;HIS 205;CYS 208(Zinc binding)

References for Catalytic Mechanism
References Sections No. of steps in catalysis
[4]
Fig.4, p.1414-1415 4
[5]
FIG.4, p.5526 4
[6]
p.10305
[7]
p.48615, p.48617
[8]
p.919-920
[9]
Fig.7, p.208 5
[10]
[11]

References
[1]
Resource
Comments
Medline ID
PubMed ID 7925414
Journal Eur J Biochem
Year 1994
Volume 224
Pages 901-7
Authors Johansson IM, Forsman C
Title Solvent hydrogen isotope effects and anion inhibition of CO2 hydration catalysed by carbonic anhydrase from Pisum sativum.
Related PDB
Related UniProtKB
[2]
Resource
Comments
Medline ID
PubMed ID 9100024
Journal Biochemistry
Year 1997
Volume 36
Pages 4287-94
Authors Bjorkbacka H, Johansson IM, Skarfstad E, Forsman C
Title The sulfhydryl groups of Cys 269 and Cys 272 are critical for the oligomeric state of chloroplast carbonic anhydrase from Pisum sativum.
Related PDB
Related UniProtKB
[3]
Resource
Comments
Medline ID
PubMed ID 9336012
Journal Pharmacol Ther
Year 1997
Volume 74
Pages 1-20
Authors Lindskog S
Title Structure and mechanism of carbonic anhydrase.
Related PDB
Related UniProtKB
[4]
Resource
Comments X-RAY CRYSTALLOGRAPHY (1.93 ANGSTROMS) OF 108-328.
Medline ID 20211383
PubMed ID 10747009
Journal EMBO J
Year 2000
Volume 19
Pages 1407-18
Authors Kimber MS, Pai EF
Title The active site architecture of Pisum sativum beta-carbonic anhydrase is a mirror image of that of alpha-carbonic anhydrases.
Related PDB 1ekj
Related UniProtKB P17067
[5]
Resource
Comments X-ray crystallography
Medline ID
PubMed ID 10681531
Journal J Biol Chem
Year 2000
Volume 275
Pages 5521-6
Authors Mitsuhashi S, Mizushima T, Yamashita E, Yamamoto M, Kumasaka T, Moriyama H, Ueki T, Miyachi S, Tsukihara T
Title X-ray structure of beta-carbonic anhydrase from the red alga, Porphyridium purpureum, reveals a novel catalytic site for CO(2) hydration.
Related PDB 1ddz
Related UniProtKB
[6]
Resource
Comments X-ray crystallography
Medline ID
PubMed ID 11096105
Journal J Biol Chem
Year 2001
Volume 276
Pages 10299-305
Authors Strop P, Smith KS, Iverson TM, Ferry JG, Rees DC
Title Crystal structure of the "cab"-type beta class carbonic anhydrase from the archaeon Methanobacterium thermoautotrophicum.
Related PDB 1g5c
Related UniProtKB
[7]
Resource
Comments
Medline ID
PubMed ID 11696553
Journal J Biol Chem
Year 2001
Volume 276
Pages 48615-8
Authors Tripp BC, Smith K, Ferry JG
Title Carbonic anhydrase: new insights for an ancient enzyme.
Related PDB
Related UniProtKB
[8]
Resource
Comments
Medline ID
PubMed ID 11316870
Journal Protein Sci
Year 2001
Volume 10
Pages 911-22
Authors Cronk JD, Endrizzi JA, Cronk MR, O'neill JW, Zhang KY
Title Crystal structure of E. coli beta-carbonic anhydrase, an enzyme with an unusual pH-dependent activity.
Related PDB 1i6o 1i6p
Related UniProtKB
[9]
Resource
Comments
Medline ID
PubMed ID 12147257
Journal Arch Biochem Biophys
Year 2002
Volume 404
Pages 197-209
Authors Rowlett RS, Tu C, McKay MM, Preiss JR, Loomis RJ, Hicks KA, Marchione RJ, Strong JA, Donovan GS Jr, Chamberlin JE
Title Kinetic characterization of wild-type and proton transfer-impaired variants of beta-carbonic anhydrase from Arabidopsis thaliana.
Related PDB
Related UniProtKB
[10]
Resource
Comments
Medline ID
PubMed ID 12484784
Journal Biochemistry
Year 2002
Volume 41
Pages 15429-35
Authors Tu C, Rowlett RS, Tripp BC, Ferry JG, Silverman DN
Title Chemical rescue of proton transfer in catalysis by carbonic anhydrases in the beta- and gamma-class.
Related PDB
Related UniProtKB
[11]
Resource
Comments
Medline ID
PubMed ID 12107142
Journal J Bacteriol
Year 2002
Volume 184
Pages 4240-5
Authors Smith KS, Ingram-Smith C, Ferry JG
Title Roles of the conserved aspartate and arginine in the catalytic mechanism of an archaeal beta-class carbonic anhydrase.
Related PDB
Related UniProtKB
[12]
Resource
Comments
Medline ID
PubMed ID 15081890
Journal Arch Biochem Biophys
Year 2004
Volume 425
Pages 25-32
Authors Rowlett RS, Tu C, Murray PS, Chamberlin JE
Title Examination of the role of Gln-158 in the mechanism of CO(2) hydration catalyzed by beta-carbonic anhydrase from Arabidopsis thaliana.
Related PDB
Related UniProtKB

Comments
This enzyme is composed of two internally repeated catalytic domains. The catalytic domains are homologous to other beta-carbonic anhydorase enzymes (see S00424 in EzCatDB).
The catalytic zinc ion is ligated by two conserved cysteine residues and a conserved histidine, together with a conserved aspartate residue (Asp151/Asp405). However, considering the temperature factor, the aspartate residue is very mobile, suggesting that this residue can be displaced by the substrate hydroxide, when it is protonated (see [5]).
According to the literature [4], [5], [7], [8], [9] & [12], the catalytic reaction proceeds as follows:
(1) A water molecule is bound to the cofactor zinc.
(2) A proton of the substrate water is abstracted by a catalytic residue, a proton shuttle residue, or solvent, to generate the hydroxide. Asp151/Asp405 acts as a general base, which deprotonates the water bound to the cofactor zinc ion. Tyr190'/Tyr444' may act as a proton shuttle, which transfers a proton to the solvent.
(3) The hydroxide bound to zinc makes a nucleophilic attack on the carbon atom of another substrate, carbon dioxide (CO2), which is stabilized by Gln140'/Gln394'. The nucleophile, the hydroxide, is also stabilized by Asp151/Asp405. This reaction leads to the formation of the product, bicarbonate anion.

Created Updated
2004-07-15 2009-02-26