DB code: S00424

RLCP classification 4.15.898520.455 : Addition
CATH domain 3.40.1050.10 : Beta-carbonic Anhydrase; Chain A Catalytic domain
E.C. 4.2.1.1
CSA 1i6p
M-CSA 1i6p
MACiE

CATH domain Related DB codes (homologues)
3.40.1050.10 : Beta-carbonic Anhydrase; Chain A S00521 D00474

Uniprot Enzyme Name
UniprotKB Protein name Synonyms Contains Pfam RefSeq
P17067 Carbonic anhydrase, chloroplastic
EC 4.2.1.1
Carbonate dehydratase
Carbonic anhydrase, 27 kDa isoform
Carbonic anhydrase, 25 kDa isoform
PF00484 (Pro_CA)
[Graphical View]
P61517 Carbonic anhydrase 2
EC 4.2.1.1
Carbonate dehydratase 2
None PF00484 (Pro_CA)
[Graphical View] 		NP_414668.1 (Protein)
NC_000913.2 (DNA/RNA sequence)
YP_488429.1 (Protein)
NC_007779.1 (DNA/RNA sequence)

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
P17067 CAHC_PEA H(2)CO(3) = CO(2) + H(2)O. Homohexamer. Plastid, chloroplast stroma.
P61517 CAN_ECOLI H(2)CO(3) = CO(2) + H(2)O. Homodimer. Binds 1 zinc ion per subunit.

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

Compound table
Cofactors Substrates Products Intermediates
KEGG-id C00038 C00001 C00011 C01353
E.C.
Compound Zinc H2O CO2 Carbonic acid
Type heavy metal H2O others carboxyl group
ChEBI 29105
 29105
 		15377
 15377
 		16526
 16526
 		28976
 28976
PubChem 32051
 32051
 		22247451
 962
 22247451
 962
 		280
 280
 		22639876
 3614646
 767
 22639876
 3614646
 767
1ekjA Bound:_ZN Unbound Unbound Analogue:ACT
1ekjB Bound:_ZN Unbound Unbound Analogue:ACT
1ekjC Bound:_ZN Unbound Bound:HOH_1001 Analogue:ACT
1ekjD Bound:_ZN Unbound Unbound Analogue:ACT
1ekjE Bound:_ZN Unbound Unbound Analogue:ACT
1ekjF Bound:_ZN Unbound Unbound Analogue:ACT
1ekjG Bound:_ZN Unbound Unbound Analogue:ACT
1ekjH Bound:_ZN Unbound Unbound Analogue:ACT
1t75A Bound:_ZN Unbound Unbound
1t75B Bound:_ZN Unbound Unbound
1t75D Bound:_ZN Unbound Unbound
1t75E Bound:_ZN Unbound Unbound
1i6oA Bound:_ZN Unbound Unbound Unbound
1i6oB Bound:_ZN Unbound Unbound Unbound
1i6pA Bound:_ZN Unbound Unbound 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
1ekjA GLN 151;ASP 162;TYR 205 CYS 160;;HIS 220;CYS 223(Zinc binding) D160 sligtly away from zinc
1ekjB GLN 151;ASP 162;TYR 205 CYS 160;;HIS 220;CYS 223(Zinc binding) D160 sligtly away from zinc
1ekjC GLN 151;ASP 162;TYR 205 CYS 160;ASP 162;HIS 220;CYS 223(Zinc binding)
1ekjD GLN 151;ASP 162;TYR 205 CYS 160;ASP 162;HIS 220;CYS 223(Zinc binding)
1ekjE GLN 151;ASP 162;TYR 205 CYS 160;;HIS 220;CYS 223(Zinc binding) D160 sligtly away from zinc
1ekjF GLN 151;ASP 162;TYR 205 CYS 160;;HIS 220;CYS 223(Zinc binding) D160 sligtly away from zinc
1ekjG GLN 151;ASP 162;TYR 205 CYS 160;ASP 162;HIS 220;CYS 223(Zinc binding)
1ekjH GLN 151;ASP 162;TYR 205 CYS 160;;HIS 220;CYS 223(Zinc binding) D160 sligtly away from zinc
1t75A GLN 33;ASP 44;TYR 83 CYS 42;ASP 44;HIS 98;CYS 101(Zinc binding)
1t75B GLN 33;ASP 44;TYR 83 CYS 42;ASP 44;HIS 98;CYS 101(Zinc binding)
1t75D GLN 33;ASP 44;TYR 83 CYS 42;ASP 44;HIS 98;CYS 101(Zinc binding)
1t75E GLN 33;ASP 44;TYR 83 CYS 42;ASP 44;HIS 98;CYS 101(Zinc binding)
1i6oA GLN 33;ASP 44;TYR 83 CYS 42;ASP 44;HIS 98;CYS 101(Zinc binding)
1i6oB GLN 33;ASP 44;TYR 83 CYS 42;ASP 44;HIS 98;CYS 101(Zinc binding)
1i6pA GLN 33;ASP 44;TYR 83 CYS 42;ASP 44;HIS 98;CYS 101(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 belongs to the beta-carbonic anhydrase family.
The catalytic zinc ion is ligated by two conserved cysteine residues and a conserved histidine, together with a conserved aspartate residue (Asp162 of 1ekj). However, in some structures, the aspartate residue is displaced, suggesting that this residue function as a switch of catalytic reaction (see [8]).
According to the literature [4], [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 general base or proton shuttle residue (which transfers a proton to the solvent), or solvent, to generate the hydroxide. This role is probably played by Tyr205' from the adjacent chain (of 1ekj). (Asp162 may act as a general base, which deprotonates 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 Gln151' from the adjacent chain (of 1ekj). The nucleophile, the hydroxide, is also stabilized by Asp162. This reaction leads to the formation of the product, bicarbonate anion.

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