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 29105	16526 16526	15377 15377	28976 28976
PubChem	32051 32051	280 280	22247451 962 22247451 962	22639876 3614646 767 22639876 3614646 767

1thjA	Bound:_ZN	Unbound		Unbound	Unbound
1thjB	Bound:_ZN	Unbound		Unbound	Unbound
1thjC	Bound:_ZN	Unbound		Unbound	Unbound
1qreA	Analogue:_CO	Unbound		Bound:BCT	Intermediate-analogue:BCT
1qrfA	Analogue:_CO	Unbound		Unbound	Unbound
1qrgA	Bound:_ZN	Unbound		Unbound	Unbound
1qrlA	Bound:_ZN	Unbound		Bound:BCT	Unbound
1qrmA	Bound:_ZN	Unbound		Unbound	Unbound
1qq0A	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	ARG 59;GLU 62;GLN 75;GLU 84;ASN 202	HIS 81;HIS 117;HIS 122(Zinc binding)
1thjB	ARG 59;GLU 62;GLN 75;GLU 84;ASN 202	HIS 81;HIS 117;HIS 122(Zinc binding)
1thjC	ARG 59;GLU 62;GLN 75;GLU 84;ASN 202	HIS 81;HIS 117;HIS 122(Zinc binding)
1qreA	ARG 59;GLU 62;GLN 75;GLU 84;ASN 202	HIS 81;HIS 117;HIS 122(Zinc binding)
1qrfA	ARG 59;GLU 62;GLN 75;GLU 84;ASN 202	HIS 81;HIS 117;HIS 122(Zinc binding)
1qrgA	ARG 59;GLU 62;GLN 75;GLU 84;ASN 202	HIS 81;HIS 117;HIS 122(Zinc binding)
1qrlA	ARG 59;GLU 62;GLN 75;GLU 84;ASN 202	HIS 81;HIS 117;HIS 122(Zinc binding)
1qrmA	ARG 59;GLU 62;GLN 75;GLU 84;ASN 202	HIS 81;HIS 117;HIS 122(Zinc binding)
1qq0A	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.

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