DB code: S00521

RLCP classification 4.15.898500.454 : Addition
CATH 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 S00424 D00474

Uniprot Enzyme Name
UniprotKB Protein name Synonyms RefSeq Pfam
Q50565
Carbonic anhydrase
NP_276694.1 (Protein)
NC_000916.1 (DNA/RNA sequence)
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
Q50565 Q50565_METTH

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
 29105
 		16526
 16526
 		15377
 15377
 		28976
 28976
PubChem 32051
 32051
 		280
 280
 		22247451
 962
 22247451
 962
 		22639876
 3614646
 767
 22639876
 3614646
 767
1g5cA Bound:_ZN Unbound Bound:HOH_1 Unbound
1g5cB Bound:_ZN Unbound Bound:HOH_2 Unbound
1g5cC Bound:_ZN Unbound Bound:HOH_3 Unbound
1g5cD Bound:_ZN Unbound Bound:HOH_4 Unbound
1g5cE Bound:_ZN Unbound Bound:HOH_6 Unbound
1g5cF Bound:_ZN Unbound Bound:HOH_5 Unbound

Reference for Active-site residues
resource references E.C.
literature [4]

Active-site residues
PDB Catalytic residues Cofactor-binding residues Modified residues Main-chain involved in catalysis Comment
1g5cA ASP 34 CYS 32; ;HIS 87;CYS 90(Zinc binding) GLY 91 D34 sligtly away from zinc
1g5cB ASP 34 CYS 32; ;HIS 87;CYS 90(Zinc binding) GLY 91 D34 sligtly away from zinc
1g5cC ASP 34 CYS 32;ASP 34;HIS 87;CYS 90(Zinc binding) GLY 91
1g5cD ASP 34 CYS 32; ;HIS 87;CYS 90(Zinc binding) GLY 91 D34 sligtly away from zinc
1g5cE ASP 34 CYS 32; ;HIS 87;CYS 90(Zinc binding) GLY 91 D34 sligtly away from zinc
1g5cF ASP 34 CYS 32; ;HIS 87;CYS 90(Zinc binding) GLY 91 D34 sligtly away from zinc

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
Although this enzyme belongs to the beta-carbonic anhydrase family, it seems to have a slightly different mechanism from that of other beta-carbonic anhydrase enzymes (see [6], [7]).
The catalytic zinc ion is ligated by two conserved cysteine residues and a conserved histidine, together with a conserved aspartate residue (Asp34).
According to the literature [6] & [7], 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 solvent water, to generate the hydroxide. Asp34 may act as a general base or a proton shuttle, which transfer a proton from the water bound to the cofactor zinc ion.
(3) The hydroxide bound to zinc makes a nucleophilic attack on the carbon atom of another substrate, carbon dioxide (CO2), which is stabilized by Gly91. The nucleophile, the hydroxide, is also stabilized by Asp34. This reaction leads to the formation of the product, bicarbonate anion.

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