DB code: S00455

RLCP classification 1.15.8000.2150 : Hydrolysis
CATH domain 3.90.80.10 : Inorganic Pyrophosphatase Catalytic domain
E.C. 3.6.1.1
CSA 1wgi
M-CSA 1wgi
MACiE

CATH domain Related DB codes (homologues)

Uniprot Enzyme Name
UniprotKB Protein name Synonyms RefSeq Pfam
P00817 Inorganic pyrophosphatase
EC 3.6.1.1
Pyrophosphate phospho-hydrolase
PPase
NP_009565.1 (Protein)
NM_001178359.1 (DNA/RNA sequence)
PF00719 (Pyrophosphatase)
[Graphical View]
P0A7A9 Inorganic pyrophosphatase
EC 3.6.1.1
Pyrophosphate phospho-hydrolase
PPase
NP_418647.1 (Protein)
NC_000913.2 (DNA/RNA sequence)
YP_492368.1 (Protein)
NC_007779.1 (DNA/RNA sequence)
PF00719 (Pyrophosphatase)
[Graphical View]
P50308 Inorganic pyrophosphatase
EC 3.6.1.1
Pyrophosphate phospho-hydrolase
PPase
YP_255610.1 (Protein)
NC_007181.1 (DNA/RNA sequence)
PF00719 (Pyrophosphatase)
[Graphical View]
P38576 Inorganic pyrophosphatase
EC 3.6.1.1
Pyrophosphate phospho-hydrolase
PPase
YP_145231.1 (Protein)
NC_006461.1 (DNA/RNA sequence)
PF00719 (Pyrophosphatase)
[Graphical View]

KEGG enzyme name
inorganic diphosphatase

UniprotKB: Accession Number Entry name Activity Subunit Subcellular location Cofactor
P00817 IPYR_YEAST Diphosphate + H(2)O = 2 phosphate. Homodimer. Cytoplasm. Binds 4 magnesium ions per subunit. Other metal ions can support activity, but at a lower rate. Two magnesium ions are required for the activation of the enzyme and are present before substrate binds, two additional magnesium ions form complexes with substrate and product (By similarity).
P0A7A9 IPYR_ECOLI Diphosphate + H(2)O = 2 phosphate. Homohexamer. Cytoplasm. Binds 4 magnesium ions per subunit. Other metal ions can support activity, but at a lower rate. Two magnesium ions are required for the activation of the enzyme and are present before substrate binds, two additional magnesium ions form complexes with substrate and product.
P50308 IPYR_SULAC Diphosphate + H(2)O = 2 phosphate. Homohexamer. Cytoplasm. Binds 4 magnesium ions per subunit. Other metal ions can support activity, but at a lower rate. Two magnesium ions are required for the activation of the enzyme and that are present before substrate binds, two additional magnesium ions form complexes with substrate and product.
P38576 IPYR_THET8 Diphosphate + H(2)O = 2 phosphate. Homohexamer. Cytoplasm. Binds 4 magnesium ions per subunit. Other metal ions can support activity, but at a lower rate. Two magnesium ions are required for the activation of the enzyme and are present before substrate binds, two additional magnesium ions form complexes with substrate and product.

KEGG Pathways
Map code Pathways E.C.
MAP00190 Oxidative phosphorylation

Compound table
Cofactors Substrates Products Intermediates
KEGG-id C00050 C00013 C00001 C00009
E.C.
Compound Metal Pyrophosphate H2O Orthophosphate
Type heavy metal phosphate group/phosphate ion H2O phosphate group/phosphate ion
ChEBI 29888
 29888
 		15377
 15377
 		26078
 26078
PubChem 1023
 21961011
 1023
 21961011
 		22247451
 962
 22247451
 962
 		1004
 22486802
 1004
 22486802
117eA Bound:4x_MN Unbound Bound:2xPO4
117eB Bound:4x_MN Unbound Bound:PO4
1e6aA Bound:4x_MN Bound:POP Unbound
1e6aB Bound:4x_MN Bound:POP Unbound
1e9gA Bound:4x_MN Unbound Bound:2xPO4
1e9gB Bound:4x_MN Unbound Bound:2xPO4
1hujA Bound:_MG Unbound Unbound
1hujB Bound:_MG Unbound Unbound
1hukA Bound:_MG Unbound Unbound
1hukB Bound:_MG Unbound Unbound
1pypA Unbound Unbound Unbound
1pypB Unbound Unbound Unbound
1wgiA Bound:2x_MN Unbound Unbound
1wgiB Bound:2x_MN Unbound Unbound
1wgjA Bound:4x_MN Unbound Bound:2xPO4
1wgjB Bound:4x_MN Unbound Bound:2xPO4
1yppA Bound:4x_MN Unbound Bound:2xPO4
1yppB Bound:4x_MN Unbound Bound:2xPO4
8prkA Bound:3x_MN Unbound Bound:PO4
8prkB Bound:3x_MN Unbound Bound:PO4
1eipA Unbound Unbound Unbound
1eipB Unbound Unbound Unbound
1fajA Unbound Unbound Unbound
1igpA Unbound Unbound Unbound
1inoA Bound:_MN Unbound Unbound
1ipwA Bound:_MG Unbound Unbound
1ipwB Bound:_MG Unbound Unbound
1jfdA Unbound Unbound Analogue:SO4
1jfdB Unbound Unbound Analogue:SO4
1mjwA Unbound Unbound Analogue:SO4
1mjwB Unbound Unbound Analogue:SO4
1mjxA Unbound Unbound Analogue:SO4
1mjxB Unbound Unbound Analogue:SO4
1mjyA Unbound Unbound Unbound
1mjyB Unbound Unbound Unbound
1mjzA Unbound Unbound Unbound
1obwA Bound:2x_MG Unbound Unbound
1obwB Bound:2x_MG Unbound Unbound
1obwC Bound:_MG Unbound Unbound
2eipA Unbound Unbound Unbound
2eipB Unbound Unbound Unbound
1qezA Bound:_MG Unbound Unbound
1qezB Bound:_MG Unbound Unbound
1qezC Bound:_MG Unbound Unbound
1qezD Bound:_MG Unbound Unbound
1qezE Bound:_MG Unbound Unbound
1qezF Bound:_MG Unbound Unbound
2prdA Unbound Unbound Analogue:SO4

Reference for Active-site residues
resource references E.C.

Active-site residues
PDB Catalytic residues Cofactor-binding residues Modified residues Main-chain involved in catalysis Comment
117eA GLU 48;LYS 56;ARG 78;TYR 93;TYR 192;LYS 193 GLU 58;ASP 115;;ASP 120;ASP 147;ASP 152(three MN2+ binding) mutant D117E
117eB GLU 1048;LYS 1056;ARG 1078;TYR 1093;TYR 1192;LYS 1193 GLU 1058;ASP 1115; ;ASP 1120;ASP 1147;ASP 1152(three MN2+ binding) mutant D1117E
1e6aA GLU 48;LYS 56;ARG 78;TYR 93;TYR 192;LYS 193 GLU 58;ASP 115;ASP 117;ASP 120;ASP 147;ASP 152(three MN2+ binding)
1e6aB GLU 1048;LYS 1056;ARG 1078;TYR 1093;TYR 1192;LYS 1193 GLU 1058;ASP 1115;ASP 1117;ASP 1120;ASP 1147;ASP 1152(three MN2+ binding)
1e9gA GLU 48;LYS 56;ARG 78;TYR 93;TYR 192;LYS 193 GLU 58;ASP 115;ASP 117;ASP 120;ASP 147;ASP 152(three MN2+ binding)
1e9gB GLU 48;LYS 56;ARG 78;TYR 93;TYR 192;LYS 193 GLU 58;ASP 115;ASP 117;ASP 120;ASP 147;ASP 152(three MN2+ binding)
1hujA GLU 48;LYS 56;ARG 78;TYR 93;TYR 192;LYS 193 GLU 58;ASP 115;ASP 117;ASP 120;ASP 147;ASP 152(three MN2+ binding)
1hujB GLU 48;LYS 56;ARG 78;TYR 93;TYR 192;LYS 193 GLU 58;ASP 115;ASP 117;ASP 120;ASP 147;ASP 152(three MN2+ binding)
1hukA GLU 48;LYS 56;ARG 78;TYR 93;TYR 192;LYS 193 GLU 58;ASP 115;ASP 117;ASP 120;ASP 147;ASP 152(three MN2+ binding)
1hukB GLU 48;LYS 56;ARG 78;TYR 93;TYR 192;LYS 193 GLU 58;ASP 115;ASP 117;ASP 120;ASP 147;ASP 152(three MN2+ binding)
1pypA GLU 48;LYS 56;ARG 77;TYR 92;TYR 191;LYS 192 GLU 58;ASP 114;;ASP 119;ASP 146;ASP 151(three MN2+ binding) mutant D116N
1pypB GLU 48;LYS 56;ARG 77;TYR 92;TYR 191;LYS 192 GLU 58;ASP 114;;ASP 119;ASP 146;ASP 151(three MN2+ binding) mutant D116N
1wgiA GLU 48;LYS 56;ARG 78;TYR 93;TYR 192;LYS 193 GLU 58;ASP 115;ASP 117;ASP 120;ASP 147;ASP 152(three MN2+ binding)
1wgiB GLU 48;LYS 56;ARG 78;TYR 93;TYR 192;LYS 193 GLU 58;ASP 115;ASP 117;ASP 120;ASP 147;ASP 152(three MN2+ binding)
1wgjA GLU 48;LYS 56;ARG 78;TYR 93;TYR 192;LYS 193 GLU 58;ASP 115;ASP 117;ASP 120;ASP 147;ASP 152(three MN2+ binding)
1wgjB GLU 48;LYS 56;ARG 78;TYR 93;TYR 192;LYS 193 GLU 58;ASP 115;ASP 117;ASP 120;ASP 147;ASP 152(three MN2+ binding)
1yppA GLU 48;LYS 56;ARG 78;TYR 93;TYR 192;LYS 193 GLU 58;ASP 115;ASP 117;ASP 120;ASP 147;ASP 152(three MN2+ binding)
1yppB GLU 48;LYS 56;ARG 78;TYR 93;TYR 192;LYS 193 GLU 58;ASP 115;ASP 117;ASP 120;ASP 147;ASP 152(three MN2+ binding)
8prkA GLU 48;LYS 56; ;TYR 93;TYR 192;LYS 193 GLU 58;ASP 115;ASP 117;ASP 120;ASP 147;ASP 152(three MN2+ binding) mutant R78K
8prkB GLU 1048;LYS 1056; ;TYR 1093;TYR 1192;LYS 1193 GLU 1058;ASP 1115;ASP 1117;ASP 1120;ASP 1147;ASP 1152(three MN2+ binding) mutant R1078K
1eipA GLU 20;LYS 29;ARG 43;TYR 55;TYR 141;LYS 142 GLU 31;ASP 65;ASP 67;ASP 70; ;ASP 102(three MN2+ binding) mutant D101E, invisible D97
1eipB GLU 20;LYS 29;ARG 43;TYR 55;TYR 141;LYS 142 GLU 31;ASP 65;ASP 67;ASP 70; ;ASP 102(three MN2+ binding) mutant D101E, invisible D97
1fajA GLU 20;LYS 29;ARG 43;TYR 55;TYR 141;LYS 142 GLU 31;ASP 65;ASP 67;ASP 70;ASP 97;ASP 102(three MN2+ binding)
1igpA GLU 20;LYS 29;ARG 43;TYR 55;TYR 141;LYS 142 GLU 31;ASP 65;ASP 67;ASP 70;ASP 97;ASP 102(three MN2+ binding)
1inoA GLU 20;LYS 29;ARG 43;TYR 55;TYR 141;LYS 142 GLU 31;ASP 65;ASP 67;ASP 70;ASP 97;ASP 102(three MN2+ binding)
1ipwA GLU 20;LYS 29;ARG 43;TYR 55;TYR 141;LYS 142 GLU 31;ASP 65;ASP 67;ASP 70;ASP 97;ASP 102(three MN2+ binding)
1ipwB GLU 20;LYS 29;ARG 43;TYR 55;TYR 141;LYS 142 GLU 31;ASP 65;ASP 67;ASP 70;ASP 97;ASP 102(three MN2+ binding)
1jfdA GLU 20;LYS 29;ARG 43;TYR 55;TYR 141;LYS 142 GLU 31;ASP 65;ASP 67;ASP 70;ASP 97;ASP 102(three MN2+ binding)
1jfdB GLU 20;LYS 29;ARG 43;TYR 55;TYR 141;LYS 142 GLU 31;ASP 65;ASP 67;ASP 70;ASP 97;ASP 102(three MN2+ binding)
1mjwA GLU 20;LYS 29;ARG 43;TYR 55;TYR 141;LYS 142 GLU 31;ASP 65;ASP 67;ASP 70;ASP 97;ASP 102(three MN2+ binding)
1mjwB GLU 20;LYS 29;ARG 43;TYR 55;TYR 141;LYS 142 GLU 31;ASP 65;ASP 67;ASP 70;ASP 97;ASP 102(three MN2+ binding)
1mjxA GLU 20;LYS 29;ARG 43;TYR 55;TYR 141;LYS 142 GLU 31; ;ASP 67;ASP 70;ASP 97;ASP 102(three MN2+ binding) mutant D65N
1mjxB GLU 20;LYS 29;ARG 43;TYR 55;TYR 141;LYS 142 GLU 31; ;ASP 67;ASP 70;ASP 97;ASP 102(three MN2+ binding) mutant D65N
1mjyA GLU 20;LYS 29;ARG 43;TYR 55;TYR 141;LYS 142 GLU 31;ASP 65;ASP 67; ;ASP 97;ASP 102(three MN2+ binding) mutant D70N
1mjyB GLU 20;LYS 29;ARG 43;TYR 55;TYR 141;LYS 142 GLU 31;ASP 65;ASP 67; ;ASP 97;ASP 102(three MN2+ binding) mutant D70N
1mjzA GLU 20;LYS 29;ARG 43;TYR 55;TYR 141;LYS 142 GLU 31;ASP 65;ASP 67;ASP 70; ;ASP 102(three MN2+ binding) mutant D97N
1obwA GLU 20;LYS 29;ARG 43;TYR 55;TYR 141;LYS 142 GLU 31;ASP 65;ASP 67;ASP 70;ASP 97;ASP 102(three MN2+ binding)
1obwB GLU 20;LYS 29;ARG 43;TYR 55;TYR 141;LYS 142 GLU 31;ASP 65;ASP 67;ASP 70;ASP 97;ASP 102(three MN2+ binding)
1obwC GLU 20;LYS 29;ARG 43;TYR 55;TYR 141;LYS 142 GLU 31;ASP 65;ASP 67;ASP 70;ASP 97;ASP 102(three MN2+ binding)
2eipA GLU 20;LYS 29;ARG 43;TYR 55;TYR 141;LYS 142 GLU 31;ASP 65;ASP 67;ASP 70;ASP 97;ASP 102(three MN2+ binding)
2eipB GLU 20;LYS 29;ARG 43;TYR 55;TYR 141;LYS 142 GLU 31;ASP 65;ASP 67;ASP 70;ASP 97;ASP 102(three MN2+ binding)
1qezA GLU 1018;LYS 1026;ARG 1040;TYR 1052;TYR 1138;LYS 1139 GLU 1028;ASP 1062;ASP 1064;ASP 1067;ASP 1094;ASP 1099(three MN2+ binding) mutant R1037K
1qezB GLU 2018;LYS 2026;ARG 2040;TYR 2052;TYR 2138;LYS 2139 GLU 2028;ASP 2062;ASP 2064;ASP 2067;ASP 2094;ASP 2099(three MN2+ binding) mutant R2037K
1qezC GLU 3018;LYS 3026;ARG 3040;TYR 3052;TYR 3138;LYS 3139 GLU 3028;ASP 3062;ASP 3064;ASP 3067;ASP 3094;ASP 3099(three MN2+ binding) mutant R3037K
1qezD GLU 4018;LYS 4026;ARG 4040;TYR 4052;TYR 4138;LYS 4139 GLU 4028;ASP 4062;ASP 4064;ASP 4067;ASP 4094;ASP 4099(three MN2+ binding) mutant R4037K
1qezE GLU 5018;LYS 5026;ARG 5040;TYR 5052;TYR 5138;LYS 5139 GLU 5028;ASP 5062;ASP 5064;ASP 5067;ASP 5094;ASP 5099(three MN2+ binding) mutant R5037K
1qezF GLU 6018;LYS 6026;ARG 6040;TYR 6052;TYR 6138;LYS 6139 GLU 6028;ASP 6062;ASP 6064;ASP 6067;ASP 6094;ASP 6099(three MN2+ binding) mutant R6037K
2prdA GLU 21;LYS 29;ARG 43;TYR 55;TYR 139;LYS 140 GLU 31;ASP 65;ASP 67;ASP 70;ASP 97;ASP 102(three MN2+ binding)

References for Catalytic Mechanism
References Sections No. of steps in catalysis
[3]
p.1101-1103
[4]
p.827-829
[6]
p.787-789
[9]
p.4660-4661
[12]
Fig.4, p.142
[13]
Fig.9, Fig.10, p.224-227
[16]
Fig.7, p.1498-1502
[18]
Fig.6, Fig.8, p.7757-7760
[21]
p.1574-1575
[22]
Fig.3, p.1756-1759
[30]
Scheme 1, p.3123-3125 3
[34]
p.637-638, p.641-642

References
[1]
Resource
Comments Similarity To E.Coli And K.Lactis Ppases.
Medline ID 90254161
PubMed ID 2160278
Journal Biochimica et Biophysica Acta
Year 1990
Volume 1038
Pages 338-45
Authors Lahti R, Kolakowski LF Jr, Heinonen J, Vihinen M, Pohjanoksa K, Cooperman BS
Title Conservation of functional residues between yeast and E. coli inorganic pyrophosphatases.
Related PDB
Related UniProtKB P00817
[2]
Resource
Comments
Medline ID
PubMed ID 1974462
Journal Biochemistry
Year 1990
Volume 29
Pages 5761-6
Authors Lahti R, Pohjanoksa K, Pitkaranta T, Heikinheimo P, Salminen T, Meyer P, Heinonen J
Title A site-directed mutagenesis study on Escherichia coli inorganic pyrophosphatase. Glutamic acid-98 and lysine-104 are important for structural integrity, whereas aspartic acids-97 and -102 are essential for catalytic activity.
Related PDB
Related UniProtKB
[3]
Resource
Comments X-ray crystallography (2.0 Angstroms)
Medline ID
PubMed ID 7920256
Journal Protein Sci
Year 1994
Volume 3
Pages 1098-107
Authors Teplyakov A, Obmolova G, Wilson KS, Ishii K, Kaji H, Samejima T, Kuranova I
Title Crystal structure of inorganic pyrophosphatase from Thermus thermophilus.
Related PDB 2prd
Related UniProtKB P38576
[4]
Resource
Comments X-ray crystallography (2.7 Angstroms)
Medline ID 95062129
PubMed ID 7971944
Journal Protein Eng, Erratum in:Protein Eng 1994 7 1173
Year 1994
Volume 7
Pages 823-30
Authors Kankare J, Neal GS, Salminen T, Glumoff T, Glumhoff T [corrected to Glumoff T, Cooperman BS, Lahti R, Goldman A
Title The structure of E.coli soluble inorganic pyrophosphatase at 2.7 A resolution.
Related PDB
Related UniProtKB P0A7A9
[5]
Resource
Comments X-ray crystallography (2.5 Angstroms)
Medline ID
PubMed ID 8034059
Journal FEBS Lett
Year 1994
Volume 348
Pages 301-4
Authors Oganessyan VYu, Kurilova SA, Vorobyeva NN, Nazarova TI, Popov AN, Lebedev AA, Avaeva SM, Harutyunyan EH
Title X-ray crystallographic studies of recombinant inorganic pyrophosphatase from Escherichia coli.
Related PDB 1igp 1ino
Related UniProtKB
[6]
Resource
Comments
Medline ID
PubMed ID 7827037
Journal Biochemistry
Year 1995
Volume 34
Pages 782-91
Authors Salminen T, Kapyla J, Heikinheimo P, Kankare J, Goldman A, Heinonen J, Baykov AA, Cooperman BS, Lahti R
Title Structure and function analysis of Escherichia coli inorganic pyrophosphatase: is a hydroxide ion the key to catalysis?
Related PDB
Related UniProtKB
[7]
Resource
Comments
Medline ID
PubMed ID 8543015
Journal FEBS Lett
Year 1995
Volume 377
Pages 44-6
Authors Avaeva SM, Rodina EV, Kurilova SA, Nazarova TI, Vorobyeva NN, Harutyunyan EH, Oganessyan VYu
Title Mg2+ activation of Escherichia coli inorganic pyrophosphatase.
Related PDB
Related UniProtKB
[8]
Resource
Comments
Medline ID
PubMed ID 8530523
Journal J Biol Chem
Year 1995
Volume 270
Pages 30804-12
Authors Baykov AA, Dudarenkov VY, Kapyla J, Salminen T, Hyytia T, Kasho VN, Husgafvel S, Cooperman BS, Goldman A, Lahti R
Title Dissociation of hexameric Escherichia coli inorganic pyrophosphatase into trimers on His-136-->Gln or His-140-->Gln substitution and its effect on enzyme catalytic properties.
Related PDB
Related UniProtKB
[9]
Resource
Comments
Medline ID
PubMed ID 8664254
Journal Biochemistry
Year 1996
Volume 35
Pages 4655-61
Authors Baykov AA, Hyytia T, Volk SE, Kasho VN, Vener AV, Goldman A, Lahti R, Cooperman BS
Title Catalysis by Escherichia coli inorganic pyrophosphatase: pH and Mg2+ dependence.
Related PDB
Related UniProtKB
[10]
Resource
Comments
Medline ID
PubMed ID 8664255
Journal Biochemistry
Year 1996
Volume 35
Pages 4662-9
Authors Volk SE, Dudarenkov VY, Kapyla J, Kasho VN, Voloshina OA, Salminen T, Goldman A, Lahti R, Baykov AA, Cooperman BS
Title Effect of E20D substitution in the active site of Escherichia coli inorganic pyrophosphatase on its quaternary structure and catalytic properties.
Related PDB
Related UniProtKB
[11]
Resource
Comments X-ray crystallography (2.2/2.3 Angstroms)
Medline ID
PubMed ID 8664256
Journal Biochemistry
Year 1996
Volume 35
Pages 4670-7
Authors Kankare J, Salminen T, Lahti R, Cooperman BS, Baykov AA, Goldman A
Title Crystallographic identification of metal-binding sites in Escherichia coli inorganic pyrophosphatase.
Related PDB 1ipw
Related UniProtKB P0A7A9
[12]
Resource
Comments
Medline ID
PubMed ID 8706698
Journal Eur J Biochem
Year 1996
Volume 239
Pages 138-43
Authors Heikinheimo P, Pohjanjoki P, Helminen A, Tasanen M, Cooperman BS, Goldman A, Baykov A, Lahti R
Title A site-directed mutagenesis study of Saccharomyces cerevisiae pyrophosphatase. Functional conservation of the active site of soluble inorganic pyrophosphatases.
Related PDB
Related UniProtKB
[13]
Resource
Comments X-ray crystallography (2.4 Angstroms)
Medline ID
PubMed ID 8706712
Journal Eur J Biochem
Year 1996
Volume 239
Pages 220-8
Authors Harutyunyan EH, Kuranova IP, Vainshtein BK, Hohne WE, Lamzin VS, Dauter Z, Teplyakov AV, Wilson KS
Title X-ray structure of yeast inorganic pyrophosphatase complexed with manganese and phosphate.
Related PDB 1ypp
Related UniProtKB
[14]
Resource
Comments
Medline ID
PubMed ID 8772181
Journal FEBS Lett
Year 1996
Volume 392
Pages 91-4
Authors Avaeva SM, Rodina EV, Kurilova SA, Nazarova TI, Vorobyeva NN
Title Effect of D42N substitution in Escherichia coli inorganic pyrophosphatase on catalytic activity and Mg2+ binding.
Related PDB
Related UniProtKB
[15]
Resource
Comments
Medline ID
PubMed ID 8980129
Journal FEBS Lett
Year 1996
Volume 399
Pages 99-102
Authors Avaeva S, Ignatov P, Kurilova S, Nazarova T, Rodina E, Vorobyeva N, Oganessyan V, Harutyunyan E
Title Escherichia coli inorganic pyrophosphatase: site-directed mutagenesis of the metal binding sites.
Related PDB
Related UniProtKB
[16]
Resource
Comments X-ray crystallography (2.2/2.0 Angstroms)
Medline ID
PubMed ID 8994974
Journal Structure
Year 1996
Volume 4
Pages 1491-508
Authors Heikinheimo P, Lehtonen J, Baykov A, Lahti R, Cooperman BS, Goldman A
Title The structural basis for pyrophosphatase catalysis.
Related PDB 1wgi 1wgj
Related UniProtKB P00817
[17]
Resource
Comments
Medline ID
PubMed ID
Journal Acta crystallographica. Section D
Year 1996
Volume 52
Pages 551-63
Authors J.A.Kankare,T.Salminen,R.Lahti,B.S.Cooperman, A.A.Baykov,A.Goldman
Title The structure of Escherichia coli inorganic pyrophosphatase at 2.2 angstroms resolution.
Related PDB 1faj 2eip
Related UniProtKB P0A7A9
[18]
Resource
Comments X-ray crystallography (1.9 Angstroms)
Medline ID
PubMed ID 9201917
Journal Biochemistry
Year 1997
Volume 36
Pages 7754-60
Authors Harutyunyan EH, Oganessyan VY, Oganessyan NN, Avaeva SM, Nazarova TI, Vorobyeva NN, Kurilova SA, Huber R, Mather T
Title Crystal structure of holo inorganic pyrophosphatase from Escherichia coli at 1.9 A resolution. Mechanism of hydrolysis.
Related PDB 1obw
Related UniProtKB
[19]
Resource
Comments X-ray crystallography (2.2 Angstroms)
Medline ID
PubMed ID 9237692
Journal FEBS Lett
Year 1997
Volume 410
Pages 502-8
Authors Avaeva S, Kurilova S, Nazarova T, Rodina E, Vorobyeva N, Sklyankina V, Grigorjeva O, Harutyunyan E, Oganessyan V, Wilson K, Dauter Z, Huber R, Mather T
Title Crystal structure of Escherichia coli inorganic pyrophosphatase complexed with SO4(2-). Ligand-induced molecular asymmetry.
Related PDB 1jfd
Related UniProtKB P0A7A9
[20]
Resource
Comments
Medline ID
PubMed ID 9457758
Journal Biochemistry (Mosc)
Year 1997
Volume 62
Pages 946-50
Authors Fabrichniy IP, Lahti R, Baykov AA
Title Effect of Asp-97-->Glu substitution on the pH dependence of catalysis by inorganic pyrophosphatase of Escherichia coli.
Related PDB
Related UniProtKB
[21]
Resource
Comments X-ray crystallography (1.85/2.15 Angstroms, active site variants)
Medline ID
PubMed ID 9878371
Journal J Mol Biol
Year 1998
Volume 284
Pages 1565-80
Authors Tuominen V, Heikinheimo P, Kajander T, Torkkel T, Hyytia T, Kapyla J, Lahti R, Cooperman BS, Goldman A
Title The R78K and D117E active-site variants of Saccharomyces cerevisiae soluble inorganic pyrophosphatase: structural studies and mechanistic implications.
Related PDB 117e 8prk
Related UniProtKB P00817
[22]
Resource
Comments
Medline ID
PubMed ID 9485300
Journal Biochemistry
Year 1998
Volume 37
Pages 1754-61
Authors Pohjanjoki P, Lahti R, Goldman A, Cooperman BS
Title Evolutionary conservation of enzymatic catalysis: quantitative comparison of the effects of mutation of aligned residues in Saccharomyces cerevisiae and Escherichia coli inorganic pyrophosphatases on enzymatic activity.
Related PDB
Related UniProtKB
[23]
Resource
Comments
Medline ID
PubMed ID 9920869
Journal J Biol Chem
Year 1999
Volume 274
Pages 3294-9
Authors Efimova IS, Salminen A, Pohjanjoki P, Lapinniemi J, Magretova NN, Cooperman BS, Goldman A, Lahti R, Baykov AA
Title Directed mutagenesis studies of the metal binding site at the subunit interface of Escherichia coli inorganic pyrophosphatase.
Related PDB
Related UniProtKB
[24]
Resource
Comments
Medline ID
PubMed ID 10095764
Journal Eur J Biochem
Year 1999
Volume 260
Pages 308-17
Authors Baykov AA, Hyytia T, Turkina MV, Efimova IS, Kasho VN, Goldman A, Cooperman BS, Lahti R
Title Functional characterization of Escherichia coli inorganic pyrophosphatase in zwitterionic buffers.
Related PDB
Related UniProtKB
[25]
Resource
Comments X-ray crystallography (2.7 Angstroms)
Medline ID
PubMed ID 10386872
Journal Protein Sci
Year 1999
Volume 8
Pages 1218-31
Authors Leppanen VM, Nummelin H, Hansen T, Lahti R, Schafer G, Goldman A
Title Sulfolobus acidocaldarius inorganic pyrophosphatase: structure, thermostability, and effect of metal ion in an archael pyrophosphatase.
Related PDB 1qez
Related UniProtKB P50308
[26]
Resource
Comments
Medline ID
PubMed ID 10618499
Journal FEBS Lett
Year 1999
Volume 464
Pages 169-73
Authors Avaeva S, Grigorjeva O, Mitkevich V, Sklyankina V, Varfolomeyev S
Title Interaction of Escherichia coli inorganic pyrophosphatase active sites.
Related PDB
Related UniProtKB
[27]
Resource
Comments
Medline ID
PubMed ID 10739480
Journal Biochemistry (Mosc)
Year 2000
Volume 65
Pages 361-72
Authors Avaeva SM
Title Active site interactions in oligomeric structures of inorganic pyrophosphatases.
Related PDB
Related UniProtKB
[28]
Resource
Comments
Medline ID
PubMed ID 11009607
Journal Biochemistry
Year 2000
Volume 39
Pages 11939-47
Authors Baykov AA, Fabrichniy IP, Pohjanjoki P, Zyryanov AB, Lahti R
Title Fluoride effects along the reaction pathway of pyrophosphatase: evidence for a second enzyme.pyrophosphate intermediate.
Related PDB
Related UniProtKB
[29]
Resource
Comments catalysis
Medline ID
PubMed ID 11076535
Journal Biochemistry
Year 2000
Volume 39
Pages 13931-8
Authors Belogurov GA, Fabrichniy IP, Pohjanjoki P, Kasho VN, Lehtihuhta E, Turkina MV, Cooperman BS, Goldman A, Baykov AA, Lahti R
Title Catalytically important ionizations along the reaction pathway of yeast pyrophosphatase.
Related PDB
Related UniProtKB
[30]
Resource
Comments X-ray crystallography (1.15/1.9 Angstroms, product complex/fluoride-inhibited complex)
Medline ID
PubMed ID 11248042
Journal Proc Natl Acad Sci U S A
Year 2001
Volume 98
Pages 3121-6
Authors Heikinheimo P, Tuominen V, Ahonen AK, Teplyakov A, Cooperman BS, Baykov AA, Lahti R, Goldman A
Title Toward a quantum-mechanical description of metal-assisted phosphoryl transfer in pyrophosphatase.
Related PDB 1e6a 1e9g
Related UniProtKB
[31]
Resource
Comments
Medline ID
PubMed ID 11279052
Journal J Biol Chem
Year 2001
Volume 276
Pages 17629-34
Authors Zyryanov AB, Pohjanjoki P, Kasho VN, Shestakov AS, Goldman A, Lahti R, Baykov AA
Title The electrophilic and leaving group phosphates in the catalytic mechanism of yeast pyrophosphatase.
Related PDB
Related UniProtKB
[32]
Resource
Comments
Medline ID
PubMed ID 11566028
Journal Arch Biochem Biophys
Year 2001
Volume 394
Pages 61-6
Authors Lopes DH, Sola-Penna M
Title Urea increases tolerance of yeast inorganic pyrophosphatase activity to ethanol: the other side of urea interaction with proteins.
Related PDB
Related UniProtKB
[33]
Resource
Comments
Medline ID
PubMed ID 11754735
Journal J Biochem (Tokyo)
Year 2002
Volume 131
Pages 53-8
Authors Masuda H, Uchiumi T, Wada M, Ichiba T, Hachimori A
Title Effects of replacement of prolines with alanines on the catalytic activity and thermostability of inorganic pyrophosphatase from thermophilic bacterium PS-3.
Related PDB
Related UniProtKB
[34]
Resource
Comments
Medline ID
PubMed ID 11846572
Journal J Mol Biol
Year 2001
Volume 314
Pages 633-45
Authors Samygina VR, Popov AN, Rodina EV, Vorobyeva NN, Lamzin VS, Polyakov KM, Kurilova SA, Nazarova TI, Avaeva SM
Title The structures of Escherichia coli inorganic pyrophosphatase complexed with Ca(2+) or CaPP(i) at atomic resolution and their mechanistic implications.
Related PDB
Related UniProtKB
[35]
Resource
Comments
Medline ID
PubMed ID 12169093
Journal Biochem J
Year 2002
Volume 367
Pages 901-6
Authors Zyryanov AB, Shestakov AS, Lahti R, Baykov AA
Title Mechanism by which metal cofactors control substrate specificity in pyrophosphatase.
Related PDB
Related UniProtKB

Comments
This enzyme belongs to the PPase family.
Each Swissprot accession number includes the following PDB data.
IPYR_YEAST;P00817;117e, 1e6a, 1e9g, 1huj, 1huk, 1pyp, 1wgi, 1wgj, 1ypp, 8prk
IPYR_ECOLI;P0A7A9;1eip, 1faj, 1igp, 1ino, 1ipw, 1jfd, 1mjw, 1mjx, 1mjy, 1mjz, 1obw, 2eip
IPYR_SULAC;P50308;1qez
IPYR_THETH;P38576;2prd
The catalysis involves an SN2 mechanism (or an associative one), in which a nucleophilic hydroxyl anion makes a direct inline attack on a phosphorus atom of the substrate, rather than an SN1 one (a dissociative mechanism), according to the literature [13] & [30].
Although an alternative mechanism has been reported, in which other water molecule coordinated to Tyr93 (PDB 117e) and Mg2+ at subsite M2 is suggested to be the nucleophile (see [18]), most papers ([12], [16], [21], [22] & [34]) suggested that the hydroxide anion bound to Asp117 (PDB 117e) and the two magnesium ions at subsites M1 and M2 should make a nucleophilic attack on the substrate. Moreover, instead of acidic residues of the enzyme, a water molecule coordinated to another magnesium at subsite M3 is suggested to function as a proton donor to the leaving group, the bridging oxygen between the two phosphorus atoms, according to some papers ([16], [21] & [22]).
The rest of residues, such as arginine and lysine residues are considered to stabilize the transition state of the reaction.
Furthermore, some papers discussed the roles of the metal ions in the catalysis ([16] & [34]). The roles are suggested as follows:
(1) lowering the pKa of the water molecule to create a nucleophilic hydroxide: mainly by the one at subsite M2
(2) orienting accurately the attacking nucleophile: mainly by the one at M1
(3) increasing the substrate electrophilicity by neutralizing its net charge: mainly by the one at M3
(4) lowering the pKa of the leaving group

Created Updated
2002-09-04 2011-02-09