DB code: D00474

RLCP classification	4.15.898510.455 : Addition
CATH domain	3.40.1050.10 : Beta-carbonic Anhydrase; Chain A	Catalytic domain
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	S00521 S00424

Uniprot Enzyme Name
UniprotKB	Protein name	Synonyms	Pfam
Q43060	Carbonic anhydrase	EC 4.2.1.1	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
Q43060	Q43060_PORCR	H(2)CO(3) = CO(2) + H(2)O.

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

1ddzA01	Bound:_ZN	Unbound		Unbound
1ddzB01	Bound:_ZN	Unbound		Unbound
1ddzA02	Bound:_ZN	Unbound		Unbound
1ddzB02	Bound:_ZN	Unbound		Unbound

Reference for Active-site residues
resource	references	E.C.
literature [7]

Active-site residues
PDB	Catalytic residues	Cofactor-binding residues	Modified residues	Main-chain involved in catalysis	Comment

1ddzA01	GLN 394;ASP 405;TYR 444	CYS 403;ASP 405;HIS 459;CYS 462(Zinc binding)
1ddzB01	GLN 394;ASP 405;TYR 444	CYS 403;ASP 405;HIS 459;CYS 462(Zinc binding)
1ddzA02	GLN 140;ASP 151;TYR 190	CYS 149;ASP 151;HIS 205;CYS 208(Zinc binding)
1ddzB02	GLN 140;ASP 151;TYR 190	CYS 149;ASP 151;HIS 205;CYS 208(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 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.

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.

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