DB code: S00167

RLCP classification 4.15.1107000.480 : Addition
CATH domain 2.160.10.10 : UDP N-Acetylglucosamine Acyltransferase; domain 1 Catalytic domain
E.C. 4.2.1.1
CSA 1qrg
M-CSA 1qrg
MACiE

CATH domain Related DB codes (homologues)
2.160.10.10 : UDP N-Acetylglucosamine Acyltransferase; domain 1 D00464 D00094 D00417

Uniprot Enzyme Name
UniprotKB Protein name Synonyms Pfam
P40881 Carbonic anhydrase
EC 4.2.1.1
PF00132 (Hexapep)
[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
P40881 CAH_METTE H(2)CO(3) = CO(2) + H(2)O. Homotetramer. Zinc.

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
1thjA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:_ZN Unbound Unbound Unbound
1thjB Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:_ZN Unbound Unbound Unbound
1thjC Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:_ZN Unbound Unbound Unbound
1qreA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Analogue:_CO Unbound Bound:BCT Intermediate-analogue:BCT
1qrfA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Analogue:_CO Unbound Unbound Unbound
1qrgA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:_ZN Unbound Unbound Unbound
1qrlA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:_ZN Unbound Bound:BCT Unbound
1qrmA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:_ZN Unbound Unbound Unbound
1qq0A Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Analogue:_CO Unbound Unbound Unbound

Reference for Active-site residues
resource references E.C.
Swiss-prot;P40881 & literature [6] & [8]

Active-site residues
PDB Catalytic residues Cofactor-binding residues Modified residues Main-chain involved in catalysis Comment
1thjA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ARG 59;GLU 62;GLN 75;GLU 84;ASN 202 HIS 81;HIS 117;HIS 122(Zinc binding)
1thjB Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ARG 59;GLU 62;GLN 75;GLU 84;ASN 202 HIS 81;HIS 117;HIS 122(Zinc binding)
1thjC Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ARG 59;GLU 62;GLN 75;GLU 84;ASN 202 HIS 81;HIS 117;HIS 122(Zinc binding)
1qreA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ARG 59;GLU 62;GLN 75;GLU 84;ASN 202 HIS 81;HIS 117;HIS 122(Zinc binding)
1qrfA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ARG 59;GLU 62;GLN 75;GLU 84;ASN 202 HIS 81;HIS 117;HIS 122(Zinc binding)
1qrgA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ARG 59;GLU 62;GLN 75;GLU 84;ASN 202 HIS 81;HIS 117;HIS 122(Zinc binding)
1qrlA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ARG 59;GLU 62;GLN 75;GLU 84;ASN 202 HIS 81;HIS 117;HIS 122(Zinc binding)
1qrmA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ARG 59;GLU 62;GLN 75;GLU 84;ASN 202 HIS 81;HIS 117;HIS 122(Zinc binding)
1qq0A Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ARG 59;GLU 62;GLN 75;GLU 84;ASN 202 HIS 81;HIS 117;HIS 122(Zinc binding)

References for Catalytic Mechanism
References Sections No. of steps in catalysis
[1]
p.2324-2325
[2]
p.13124-13127
[3]
Fig.5, p.9228-9229 2
[4]
p.9237-9239
[5]
p.338
[7]
p.48617
[8]
p.675-676

References
[1]
Resource
Comments X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS).
Medline ID 96221292
PubMed ID 8665839
Journal EMBO J
Year 1996
Volume 15
Pages 2323-30
Authors Kisker C, Schindelin H, Alber BE, Ferry JG, Rees DC
Title A left-hand beta-helix revealed by the crystal structure of a carbonic anhydrase from the archaeon Methanosarcina thermophila.
Related PDB 1thj
Related UniProtKB P40881
[2]
Resource
Comments
Medline ID
PubMed ID 10529183
Journal Biochemistry
Year 1999
Volume 38
Pages 13119-28
Authors Alber BE, Colangelo CM, Dong J, Stalhandske CM, Baird TT, Tu C, Fierke CA, Silverman DN, Scott RA, Ferry JG
Title Kinetic and spectroscopic characterization of the gamma-carbonic anhydrase from the methanoarchaeon Methanosarcina thermophila.
Related PDB
Related UniProtKB
[3]
Resource
Comments X-RAY CRYSTALLOGRAPHY (1.46 ANGSTROMS).
Medline ID 20384208
PubMed ID 10924115
Journal Biochemistry
Year 2000
Volume 39
Pages 9222-31
Authors Iverson TM, Alber BE, Kisker C, Ferry JG, Rees DC
Title A closer look at the active site of gamma-class carbonic anhydrases: high-resolution crystallographic studies of the carbonic anhydrase from Methanosarcina thermophila.
Related PDB 1qre 1qrf 1qrg 1qrl 1qrm 1qq0
Related UniProtKB P40881
[4]
Resource
Comments
Medline ID
PubMed ID 10924116
Journal Biochemistry
Year 2000
Volume 39
Pages 9232-40
Authors Tripp BC, Ferry JG
Title A structure-function study of a proton transport pathway in the gamma-class carbonic anhydrase from Methanosarcina thermophila.
Related PDB
Related UniProtKB
[5]
Resource
Comments
Medline ID
PubMed ID 10978542
Journal FEMS Microbiol Rev
Year 2000
Volume 24
Pages 335-66
Authors Smith KS, Ferry JG
Title Prokaryotic carbonic anhydrases.
Related PDB
Related UniProtKB
[6]
Resource
Comments
Medline ID
PubMed ID 11414818
Journal J Am Chem Soc
Year 2001
Volume 123
Pages 5861-6
Authors Tu C, Tripp BC, Ferry JG, Silverman DN
Title Bicarbonate as a proton donor in catalysis by Zn(II)- and Co(II)-containing carbonic anhydrases.
Related PDB
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 11781108
Journal Biochemistry
Year 2002
Volume 41
Pages 669-78
Authors Tripp BC, Tu C, Ferry JG
Title Role of arginine 59 in the gamma-class carbonic anhydrases.
Related PDB
Related UniProtKB
[9]
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

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.

Created Updated
2004-06-28 2009-02-26