EzCatDB: D00474
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DB codeD00474
RLCP classification4.15.898510.455 : Addition
CATH domainDomain 13.40.1050.10 : Beta-carbonic Anhydrase; Chain ACatalytic domain
Domain 23.40.1050.10 : Beta-carbonic Anhydrase; Chain ACatalytic domain
E.C.4.2.1.1

CATH domainRelated DB codes (homologues)
3.40.1050.10 : Beta-carbonic Anhydrase; Chain AS00521,S00424

Enzyme Name
UniProtKBKEGG

Q43060
Protein nameCarbonic anhydrasecarbonate dehydratase
carbonic anhydrase
anhydrase
carbonate anhydrase
carbonic acid anhydrase
carboxyanhydrase
carbonic anhydrase A
carbonate hydro-lyase
SynonymsEC 4.2.1.1
PfamPF00484 (Pro_CA)
[Graphical view]

KEGG pathways
MAP codePathways
MAP00910Nitrogen metabolism

UniProtKB:Accession NumberQ43060
Entry nameQ43060_PORCR
ActivityH(2)CO(3) = CO(2) + H(2)O.
Subunit
Subcellular location
Cofactor

Compound table: links to PDB-related databases & PoSSuM

CofactorsSubstratesProducts
KEGG-idC00038C00011C00001C01353
CompoundZincCO2H2OCarbonic acid
Typeheavy metalothersH2Ocarboxyl group
ChEBI29105
16526
15377
28976
PubChem32051
280
962
22247451
767
3614646
22639876
            
1ddzA01Bound:_ZNUnbound Unbound
1ddzB01Bound:_ZNUnbound Unbound
1ddzA02Bound:_ZNUnbound Unbound
1ddzB02Bound:_ZNUnbound Unbound

Active-site residues
resource
literature [7]
pdbCatalytic residuesCofactor-binding residues
          
1ddzA01GLN 394;ASP 405;TYR 444
CYS 403;ASP 405;HIS 459;CYS 462(Zinc binding)
1ddzB01GLN 394;ASP 405;TYR 444
CYS 403;ASP 405;HIS 459;CYS 462(Zinc binding)
1ddzA02GLN 140;ASP 151;TYR 190
CYS 149;ASP 151;HIS 205;CYS 208(Zinc binding)
1ddzB02GLN 140;ASP 151;TYR 190
CYS 149;ASP 151;HIS 205;CYS 208(Zinc binding)

References for Catalytic Mechanism
ReferencesSectionsNo. of steps in catalysis
[4]Fig.4, p.1414-14154
[5]FIG.4, p.55264
[6]p.10305
[7]p.48615, p.48617
[8]p.919-920
[9]Fig.7, p.2085
[10]

[11]


references
[1]
PubMed ID7925414
JournalEur J Biochem
Year1994
Volume224
Pages901-7
AuthorsJohansson IM, Forsman C
TitleSolvent hydrogen isotope effects and anion inhibition of CO2 hydration catalysed by carbonic anhydrase from Pisum sativum.
[2]
PubMed ID9100024
JournalBiochemistry
Year1997
Volume36
Pages4287-94
AuthorsBjorkbacka H, Johansson IM, Skarfstad E, Forsman C
TitleThe sulfhydryl groups of Cys 269 and Cys 272 are critical for the oligomeric state of chloroplast carbonic anhydrase from Pisum sativum.
[3]
PubMed ID9336012
JournalPharmacol Ther
Year1997
Volume74
Pages1-20
AuthorsLindskog S
TitleStructure and mechanism of carbonic anhydrase.
[4]
CommentsX-RAY CRYSTALLOGRAPHY (1.93 ANGSTROMS) OF 108-328.
Medline ID20211383
PubMed ID10747009
JournalEMBO J
Year2000
Volume19
Pages1407-18
AuthorsKimber MS, Pai EF
TitleThe active site architecture of Pisum sativum beta-carbonic anhydrase is a mirror image of that of alpha-carbonic anhydrases.
Related PDB1ekj
Related UniProtKBP17067
[5]
CommentsX-ray crystallography
PubMed ID10681531
JournalJ Biol Chem
Year2000
Volume275
Pages5521-6
AuthorsMitsuhashi S, Mizushima T, Yamashita E, Yamamoto M, Kumasaka T, Moriyama H, Ueki T, Miyachi S, Tsukihara T
TitleX-ray structure of beta-carbonic anhydrase from the red alga, Porphyridium purpureum, reveals a novel catalytic site for CO(2) hydration.
Related PDB1ddz
[6]
CommentsX-ray crystallography
PubMed ID11096105
JournalJ Biol Chem
Year2001
Volume276
Pages10299-305
AuthorsStrop P, Smith KS, Iverson TM, Ferry JG, Rees DC
TitleCrystal structure of the "cab"-type beta class carbonic anhydrase from the archaeon Methanobacterium thermoautotrophicum.
Related PDB1g5c
[7]
PubMed ID11696553
JournalJ Biol Chem
Year2001
Volume276
Pages48615-8
AuthorsTripp BC, Smith K, Ferry JG
TitleCarbonic anhydrase: new insights for an ancient enzyme.
[8]
PubMed ID11316870
JournalProtein Sci
Year2001
Volume10
Pages911-22
AuthorsCronk JD, Endrizzi JA, Cronk MR, O'neill JW, Zhang KY
TitleCrystal structure of E. coli beta-carbonic anhydrase, an enzyme with an unusual pH-dependent activity.
Related PDB1i6o,1i6p
[9]
PubMed ID12147257
JournalArch Biochem Biophys
Year2002
Volume404
Pages197-209
AuthorsRowlett RS, Tu C, McKay MM, Preiss JR, Loomis RJ, Hicks KA, Marchione RJ, Strong JA, Donovan GS Jr, Chamberlin JE
TitleKinetic characterization of wild-type and proton transfer-impaired variants of beta-carbonic anhydrase from Arabidopsis thaliana.
[10]
PubMed ID12484784
JournalBiochemistry
Year2002
Volume41
Pages15429-35
AuthorsTu C, Rowlett RS, Tripp BC, Ferry JG, Silverman DN
TitleChemical rescue of proton transfer in catalysis by carbonic anhydrases in the beta- and gamma-class.
[11]
PubMed ID12107142
JournalJ Bacteriol
Year2002
Volume184
Pages4240-5
AuthorsSmith KS, Ingram-Smith C, Ferry JG
TitleRoles of the conserved aspartate and arginine in the catalytic mechanism of an archaeal beta-class carbonic anhydrase.
[12]
PubMed ID15081890
JournalArch Biochem Biophys
Year2004
Volume425
Pages25-32
AuthorsRowlett RS, Tu C, Murray PS, Chamberlin JE
TitleExamination of the role of Gln-158 in the mechanism of CO(2) hydration catalyzed by beta-carbonic anhydrase from Arabidopsis thaliana.

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.

createdupdated
2004-07-152009-02-26


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