EzCatDB: S00167

DB codeS00167
RLCP classification4.15.1107000.480
CATH domainDomain 12.160.10.10Catalytic domain
E.C.4.2.1.1
CSA1qrg

CATH domainRelated DB codes (homologues)
2.160.10.10D00464,D00094,D00417

Enzyme Name
Swiss-protKEGG

P40881
Protein nameCarbonic anhydrasecarbonate dehydratase
carbonic anhydrase
anhydrase
carbonate anhydrase
carbonic acid anhydrase
carboxyanhydrase
carbonic anhydrase A
carbonate hydro-lyase
SynonymsEC 4.2.1.1

KEGG pathways
MAP codePathways
MAP00910Nitrogen metabolism

Swiss-prot:Accession NumberP40881
Entry nameCAH_METTE
ActivityH(2)CO(3) = CO(2) + H(2)O.
SubunitHomotetramer.
Subcellular location
CofactorZinc.


CofactorsSubstratesProductsintermediates
KEGG-idC00038C00011C00001C01353
CompoundZincCO2H2OCarbonic acid
Typeheavy metalothersH2Ocarboxyl group
1thjABound:_ZNUnbound
UnboundUnbound
1thjBBound:_ZNUnbound
UnboundUnbound
1thjCBound:_ZNUnbound
UnboundUnbound
1qreAAnalogue:_COUnbound
Bound:BCTIntermediate-analogue:BCT
1qrfAAnalogue:_COUnbound
UnboundUnbound
1qrgABound:_ZNUnbound
UnboundUnbound
1qrlABound:_ZNUnbound
Bound:BCTUnbound
1qrmABound:_ZNUnbound
UnboundUnbound
1qq0AAnalogue:_COUnbound
UnboundUnbound

Active-site residues
resource
Swiss-prot;P40881 & literature [6] & [8]
pdbCatalytic residuesCofactor-binding residues
1thjAARG 59;GLU 62;GLN 75;GLU 84;ASN 202
HIS 81;HIS 117;HIS 122(Zinc binding)
1thjBARG 59;GLU 62;GLN 75;GLU 84;ASN 202
HIS 81;HIS 117;HIS 122(Zinc binding)
1thjCARG 59;GLU 62;GLN 75;GLU 84;ASN 202
HIS 81;HIS 117;HIS 122(Zinc binding)
1qreAARG 59;GLU 62;GLN 75;GLU 84;ASN 202
HIS 81;HIS 117;HIS 122(Zinc binding)
1qrfAARG 59;GLU 62;GLN 75;GLU 84;ASN 202
HIS 81;HIS 117;HIS 122(Zinc binding)
1qrgAARG 59;GLU 62;GLN 75;GLU 84;ASN 202
HIS 81;HIS 117;HIS 122(Zinc binding)
1qrlAARG 59;GLU 62;GLN 75;GLU 84;ASN 202
HIS 81;HIS 117;HIS 122(Zinc binding)
1qrmAARG 59;GLU 62;GLN 75;GLU 84;ASN 202
HIS 81;HIS 117;HIS 122(Zinc binding)
1qq0AARG 59;GLU 62;GLN 75;GLU 84;ASN 202
HIS 81;HIS 117;HIS 122(Zinc binding)

References for Catalytic Mechanism
ReferencesSectionsNo. of steps in catalysis
[1]p.2324-2325
[2]p.13124-13127
[3]Fig.5, p.9228-92292
[4]p.9237-9239
[5]p.338
[7]p.48617
[8]p.675-676

references
[1]
CommentsX-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS).
Medline ID96221292
PubMed ID8665839
JournalEMBO J
Year1996
Volume15
Pages2323-30
AuthorsKisker C, Schindelin H, Alber BE, Ferry JG, Rees DC
TitleA left-hand beta-helix revealed by the crystal structure of a carbonic anhydrase from the archaeon Methanosarcina thermophila.
Related PDB1thj
Related Swiss-protP40881
[2]
PubMed ID10529183
JournalBiochemistry
Year1999
Volume38
Pages13119-28
AuthorsAlber BE, Colangelo CM, Dong J, Stalhandske CM, Baird TT, Tu C, Fierke CA, Silverman DN, Scott RA, Ferry JG
TitleKinetic and spectroscopic characterization of the gamma-carbonic anhydrase from the methanoarchaeon Methanosarcina thermophila.
[3]
CommentsX-RAY CRYSTALLOGRAPHY (1.46 ANGSTROMS).
Medline ID20384208
PubMed ID10924115
JournalBiochemistry
Year2000
Volume39
Pages9222-31
AuthorsIverson TM, Alber BE, Kisker C, Ferry JG, Rees DC
TitleA closer look at the active site of gamma-class carbonic anhydrases: high-resolution crystallographic studies of the carbonic anhydrase from Methanosarcina thermophila.
Related PDB1qre,1qrf,1qrg,1qrl,1qrm,1qq0
Related Swiss-protP40881
[4]
PubMed ID10924116
JournalBiochemistry
Year2000
Volume39
Pages9232-40
AuthorsTripp BC, Ferry JG
TitleA structure-function study of a proton transport pathway in the gamma-class carbonic anhydrase from Methanosarcina thermophila.
[5]
PubMed ID10978542
JournalFEMS Microbiol Rev
Year2000
Volume24
Pages335-66
AuthorsSmith KS, Ferry JG
TitleProkaryotic carbonic anhydrases.
[6]
PubMed ID11414818
JournalJ Am Chem Soc
Year2001
Volume123
Pages5861-6
AuthorsTu C, Tripp BC, Ferry JG, Silverman DN
TitleBicarbonate as a proton donor in catalysis by Zn(II)- and Co(II)-containing carbonic anhydrases.
[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 ID11781108
JournalBiochemistry
Year2002
Volume41
Pages669-78
AuthorsTripp BC, Tu C, Ferry JG
TitleRole of arginine 59 in the gamma-class carbonic anhydrases.
[9]
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.

comments
This enzyme is belongs to the gamma -carbonic anhydorase enzyme family.
The catalytic zinc ion is ligated by three conserved histidine residues in a trigonal bipyramidal geometry with two more water ligands. (When cobalt ion is bound to this enzyme, the geometry is octahedral.) (see [3]). One of the ligating histidine residues, His117, is from a next chain.
According to the literature [3], [4], [7] & [8], 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 proton shuttle residue, to generate the hydroxide. The proton of the zinc-bound water is transferred through Glu62 to Glu84. Thus, Glu62 acts as a general base to deprotonate the water, whilst Glu84 acts as a proton shuttle residue, which transfer the proton to the solvent.
(3) The hydroxide bound to the zinc makes a nucleophilic attack on the carbon atom of another substrate, carbon dioxide (CO2), which is probably stabilized by Arg59, Gln75' or Asn202' from the adjacent chain. (This attack seems to be SN1-like, according to the literature [3].) The nucleophile, the hydroxide, is also stabilized by Asp62. This reaction leads to the formation of the product, bicarbonate anion.

createdupdated
2004-06-282009-02-26


Copyright: Nozomi Nagano, JST & CBRC-AIST
Funded by PRESTO/Japan Science and Technology Corporation (JST) (December 2001 - November 2004)
Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2005 - March 2006)
Funded by Grant-in-Aid for Scientific Research (B)/Japan Society for the Promotion of Science (JSPS) (April 2005 - March 2008)
Funded by BIRD/Japan Science and Technology Corporation (JST) (September 2005 - September 2010)
Funded by BIRD/Japan Science and Technology Corporation (JST) (October 2007 - September 2010)
Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2011 - March 2012)

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