EzCatDB: S00455

DB codeS00455
RLCP classification1.15.8000.2150
CATH domainDomain 13.90.80.10Catalytic domain
E.C.3.6.1.1
CSA1wgi


Enzyme Name
Swiss-protKEGG

P00817P0A7A9P50308P38576
Protein nameInorganic pyrophosphataseInorganic pyrophosphataseInorganic pyrophosphataseInorganic pyrophosphataseinorganic diphosphatase
SynonymsEC 3.6.1.1
Pyrophosphate phospho-hydrolase
PPase
EC 3.6.1.1
Pyrophosphate phospho-hydrolase
PPase
EC 3.6.1.1
Pyrophosphate phospho-hydrolase
PPase
EC 3.6.1.1
Pyrophosphate phospho-hydrolase
PPase

KEGG pathways
MAP codePathways
MAP00190Oxidative phosphorylation

Swiss-prot:Accession NumberP00817P0A7A9P50308P38576
Entry nameIPYR_YEASTIPYR_ECOLIIPYR_SULACIPYR_THET8
ActivityDiphosphate + H(2)O = 2 phosphate.Diphosphate + H(2)O = 2 phosphate.Diphosphate + H(2)O = 2 phosphate.Diphosphate + H(2)O = 2 phosphate.
SubunitHomodimer.Homohexamer.Homohexamer.Homohexamer.
Subcellular locationCytoplasm.Cytoplasm.Cytoplasm.Cytoplasm.
CofactorBinds 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).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.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.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.


CofactorsSubstratesProducts
KEGG-idC00050C00013C00001C00009
CompoundMetalPyrophosphateH2OOrthophosphate
Typeheavy metalphosphate group/phosphate ionH2Ophosphate group/phosphate ion
117eABound:4x_MNUnbound
Bound:2xPO4
117eBBound:4x_MNUnbound
Bound:PO4
1e6aABound:4x_MNBound:POP
Unbound
1e6aBBound:4x_MNBound:POP
Unbound
1e9gABound:4x_MNUnbound
Bound:2xPO4
1e9gBBound:4x_MNUnbound
Bound:2xPO4
1hujABound:_MGUnbound
Unbound
1hujBBound:_MGUnbound
Unbound
1hukABound:_MGUnbound
Unbound
1hukBBound:_MGUnbound
Unbound
1pypAUnboundUnbound
Unbound
1pypBUnboundUnbound
Unbound
1wgiABound:2x_MNUnbound
Unbound
1wgiBBound:2x_MNUnbound
Unbound
1wgjABound:4x_MNUnbound
Bound:2xPO4
1wgjBBound:4x_MNUnbound
Bound:2xPO4
1yppABound:4x_MNUnbound
Bound:2xPO4
1yppBBound:4x_MNUnbound
Bound:2xPO4
8prkABound:3x_MNUnbound
Bound:PO4
8prkBBound:3x_MNUnbound
Bound:PO4
1eipAUnboundUnbound
Unbound
1eipBUnboundUnbound
Unbound
1fajAUnboundUnbound
Unbound
1igpAUnboundUnbound
Unbound
1inoABound:_MNUnbound
Unbound
1ipwABound:_MGUnbound
Unbound
1ipwBBound:_MGUnbound
Unbound
1jfdAUnboundUnbound
Analogue:SO4
1jfdBUnboundUnbound
Analogue:SO4
1mjwAUnboundUnbound
Analogue:SO4
1mjwBUnboundUnbound
Analogue:SO4
1mjxAUnboundUnbound
Analogue:SO4
1mjxBUnboundUnbound
Analogue:SO4
1mjyAUnboundUnbound
Unbound
1mjyBUnboundUnbound
Unbound
1mjzAUnboundUnbound
Unbound
1obwABound:2x_MGUnbound
Unbound
1obwBBound:2x_MGUnbound
Unbound
1obwCBound:_MGUnbound
Unbound
2eipAUnboundUnbound
Unbound
2eipBUnboundUnbound
Unbound
1qezABound:_MGUnbound
Unbound
1qezBBound:_MGUnbound
Unbound
1qezCBound:_MGUnbound
Unbound
1qezDBound:_MGUnbound
Unbound
1qezEBound:_MGUnbound
Unbound
1qezFBound:_MGUnbound
Unbound
2prdAUnboundUnbound
Analogue:SO4

Active-site residues
pdbCatalytic residuesCofactor-binding residuescomment
117eAGLU   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
117eBGLU 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
1e6aAGLU   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)

1e6aBGLU 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)

1e9gAGLU   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)

1e9gBGLU   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)

1hujAGLU   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)

1hujBGLU   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)

1hukAGLU   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)

1hukBGLU   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)

1pypAGLU   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
1pypBGLU   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
1wgiAGLU   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)

1wgiBGLU   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)

1wgjAGLU   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)

1wgjBGLU   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)

1yppAGLU   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)

1yppBGLU   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)

8prkAGLU   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
8prkBGLU 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
1eipAGLU   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
1eipBGLU   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
1fajAGLU   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)

1igpAGLU   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)

1inoAGLU   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)

1ipwAGLU   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)

1ipwBGLU   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)

1jfdAGLU   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)

1jfdBGLU   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)

1mjwAGLU   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)

1mjwBGLU   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)

1mjxAGLU   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
1mjxBGLU   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
1mjyAGLU   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
1mjyBGLU   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
1mjzAGLU   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
1obwAGLU   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)

1obwBGLU   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)

1obwCGLU   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)

2eipAGLU   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)

2eipBGLU   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)

1qezAGLU 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
1qezBGLU 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
1qezCGLU 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
1qezDGLU 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
1qezEGLU 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
1qezFGLU 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
2prdAGLU   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
ReferencesSectionsNo. 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.3123-31253
[34]p.637-638, p.641-642

references
[1]
CommentsSimilarity To E.Coli And K.Lactis Ppases.
Medline ID90254161
PubMed ID2160278
JournalBiochimica et Biophysica Acta
Year1990
Volume1038
Pages338-45
AuthorsLahti R, Kolakowski LF Jr, Heinonen J, Vihinen M, Pohjanoksa K, Cooperman BS
TitleConservation of functional residues between yeast and E. coli inorganic pyrophosphatases.
Related Swiss-protP00817
[2]
PubMed ID1974462
JournalBiochemistry
Year1990
Volume29
Pages5761-6
AuthorsLahti R, Pohjanoksa K, Pitkaranta T, Heikinheimo P, Salminen T, Meyer P, Heinonen J
TitleA 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.
[3]
CommentsX-ray crystallography (2.0 Angstroms)
PubMed ID7920256
JournalProtein Sci
Year1994
Volume3
Pages1098-107
AuthorsTeplyakov A, Obmolova G, Wilson KS, Ishii K, Kaji H, Samejima T, Kuranova I
TitleCrystal structure of inorganic pyrophosphatase from Thermus thermophilus.
Related PDB2prd
Related Swiss-protP38576
[4]
CommentsX-ray crystallography (2.7 Angstroms)
Medline ID95062129
PubMed ID7971944
JournalProtein Eng, Erratum in:Protein Eng 1994 7 1173
Year1994
Volume7
Pages823-30
AuthorsKankare J, Neal GS, Salminen T, Glumoff T, Glumhoff T [corrected to Glumoff T, Cooperman BS, Lahti R, Goldman A
TitleThe structure of E.coli soluble inorganic pyrophosphatase at 2.7 A resolution.
Related Swiss-protP0A7A9
[5]
CommentsX-ray crystallography (2.5 Angstroms)
PubMed ID8034059
JournalFEBS Lett
Year1994
Volume348
Pages301-4
AuthorsOganessyan VYu, Kurilova SA, Vorobyeva NN, Nazarova TI, Popov AN, Lebedev AA, Avaeva SM, Harutyunyan EH
TitleX-ray crystallographic studies of recombinant inorganic pyrophosphatase from Escherichia coli.
Related PDB1igp,1ino
[6]
PubMed ID7827037
JournalBiochemistry
Year1995
Volume34
Pages782-91
AuthorsSalminen T, Kapyla J, Heikinheimo P, Kankare J, Goldman A, Heinonen J, Baykov AA, Cooperman BS, Lahti R
TitleStructure and function analysis of Escherichia coli inorganic pyrophosphatase: is a hydroxide ion the key to catalysis?
[7]
PubMed ID8543015
JournalFEBS Lett
Year1995
Volume377
Pages44-6
AuthorsAvaeva SM, Rodina EV, Kurilova SA, Nazarova TI, Vorobyeva NN, Harutyunyan EH, Oganessyan VYu
TitleMg2+ activation of Escherichia coli inorganic pyrophosphatase.
[8]
PubMed ID8530523
JournalJ Biol Chem
Year1995
Volume270
Pages30804-12
AuthorsBaykov AA, Dudarenkov VY, Kapyla J, Salminen T, Hyytia T, Kasho VN, Husgafvel S, Cooperman BS, Goldman A, Lahti R
TitleDissociation of hexameric Escherichia coli inorganic pyrophosphatase into trimers on His-136-->Gln or His-140-->Gln substitution and its effect on enzyme catalytic properties.
[9]
PubMed ID8664254
JournalBiochemistry
Year1996
Volume35
Pages4655-61
AuthorsBaykov AA, Hyytia T, Volk SE, Kasho VN, Vener AV, Goldman A, Lahti R, Cooperman BS
TitleCatalysis by Escherichia coli inorganic pyrophosphatase: pH and Mg2+ dependence.
[10]
PubMed ID8664255
JournalBiochemistry
Year1996
Volume35
Pages4662-9
AuthorsVolk SE, Dudarenkov VY, Kapyla J, Kasho VN, Voloshina OA, Salminen T, Goldman A, Lahti R, Baykov AA, Cooperman BS
TitleEffect of E20D substitution in the active site of Escherichia coli inorganic pyrophosphatase on its quaternary structure and catalytic properties.
[11]
CommentsX-ray crystallography (2.2/2.3 Angstroms)
PubMed ID8664256
JournalBiochemistry
Year1996
Volume35
Pages4670-7
AuthorsKankare J, Salminen T, Lahti R, Cooperman BS, Baykov AA, Goldman A
TitleCrystallographic identification of metal-binding sites in Escherichia coli inorganic pyrophosphatase.
Related PDB1ipw
Related Swiss-protP0A7A9
[12]
PubMed ID8706698
JournalEur J Biochem
Year1996
Volume239
Pages138-43
AuthorsHeikinheimo P, Pohjanjoki P, Helminen A, Tasanen M, Cooperman BS, Goldman A, Baykov A, Lahti R
TitleA site-directed mutagenesis study of Saccharomyces cerevisiae pyrophosphatase. Functional conservation of the active site of soluble inorganic pyrophosphatases.
[13]
CommentsX-ray crystallography (2.4 Angstroms)
PubMed ID8706712
JournalEur J Biochem
Year1996
Volume239
Pages220-8
AuthorsHarutyunyan EH, Kuranova IP, Vainshtein BK, Hohne WE, Lamzin VS, Dauter Z, Teplyakov AV, Wilson KS
TitleX-ray structure of yeast inorganic pyrophosphatase complexed with manganese and phosphate.
Related PDB1ypp
[14]
PubMed ID8772181
JournalFEBS Lett
Year1996
Volume392
Pages91-4
AuthorsAvaeva SM, Rodina EV, Kurilova SA, Nazarova TI, Vorobyeva NN
TitleEffect of D42N substitution in Escherichia coli inorganic pyrophosphatase on catalytic activity and Mg2+ binding.
[15]
PubMed ID8980129
JournalFEBS Lett
Year1996
Volume399
Pages99-102
AuthorsAvaeva S, Ignatov P, Kurilova S, Nazarova T, Rodina E, Vorobyeva N, Oganessyan V, Harutyunyan E
TitleEscherichia coli inorganic pyrophosphatase: site-directed mutagenesis of the metal binding sites.
[16]
CommentsX-ray crystallography (2.2/2.0 Angstroms)
PubMed ID8994974
JournalStructure
Year1996
Volume4
Pages1491-508
AuthorsHeikinheimo P, Lehtonen J, Baykov A, Lahti R, Cooperman BS, Goldman A
TitleThe structural basis for pyrophosphatase catalysis.
Related PDB1wgi,1wgj
Related Swiss-protP00817
[17]
JournalActa crystallographica. Section D
Year1996
Volume52
Pages551-63
AuthorsJ.A.Kankare,T.Salminen,R.Lahti,B.S.Cooperman, A.A.Baykov,A.Goldman
TitleThe structure of Escherichia coli inorganic pyrophosphatase at 2.2 angstroms resolution.
Related PDB1faj,2eip
Related Swiss-protP0A7A9
[18]
CommentsX-ray crystallography (1.9 Angstroms)
PubMed ID9201917
JournalBiochemistry
Year1997
Volume36
Pages7754-60
AuthorsHarutyunyan EH, Oganessyan VY, Oganessyan NN, Avaeva SM, Nazarova TI, Vorobyeva NN, Kurilova SA, Huber R, Mather T
TitleCrystal structure of holo inorganic pyrophosphatase from Escherichia coli at 1.9 A resolution. Mechanism of hydrolysis.
Related PDB1obw
[19]
CommentsX-ray crystallography (2.2 Angstroms)
PubMed ID9237692
JournalFEBS Lett
Year1997
Volume410
Pages502-8
AuthorsAvaeva 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
TitleCrystal structure of Escherichia coli inorganic pyrophosphatase complexed with SO4(2-). Ligand-induced molecular asymmetry.
Related PDB1jfd
Related Swiss-protP0A7A9
[20]
PubMed ID9457758
JournalBiochemistry (Mosc)
Year1997
Volume62
Pages946-50
AuthorsFabrichniy IP, Lahti R, Baykov AA
TitleEffect of Asp-97-->Glu substitution on the pH dependence of catalysis by inorganic pyrophosphatase of Escherichia coli.
[21]
CommentsX-ray crystallography (1.85/2.15 Angstroms, active site variants)
PubMed ID9878371
JournalJ Mol Biol
Year1998
Volume284
Pages1565-80
AuthorsTuominen V, Heikinheimo P, Kajander T, Torkkel T, Hyytia T, Kapyla J, Lahti R, Cooperman BS, Goldman A
TitleThe R78K and D117E active-site variants of Saccharomyces cerevisiae soluble inorganic pyrophosphatase: structural studies and mechanistic implications.
Related PDB117e,8prk
Related Swiss-protP00817
[22]
PubMed ID9485300
JournalBiochemistry
Year1998
Volume37
Pages1754-61
AuthorsPohjanjoki P, Lahti R, Goldman A, Cooperman BS
TitleEvolutionary 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.
[23]
PubMed ID9920869
JournalJ Biol Chem
Year1999
Volume274
Pages3294-9
AuthorsEfimova IS, Salminen A, Pohjanjoki P, Lapinniemi J, Magretova NN, Cooperman BS, Goldman A, Lahti R, Baykov AA
TitleDirected mutagenesis studies of the metal binding site at the subunit interface of Escherichia coli inorganic pyrophosphatase.
[24]
PubMed ID10095764
JournalEur J Biochem
Year1999
Volume260
Pages308-17
AuthorsBaykov AA, Hyytia T, Turkina MV, Efimova IS, Kasho VN, Goldman A, Cooperman BS, Lahti R
TitleFunctional characterization of Escherichia coli inorganic pyrophosphatase in zwitterionic buffers.
[25]
CommentsX-ray crystallography (2.7 Angstroms)
PubMed ID10386872
JournalProtein Sci
Year1999
Volume8
Pages1218-31
AuthorsLeppanen VM, Nummelin H, Hansen T, Lahti R, Schafer G, Goldman A
TitleSulfolobus acidocaldarius inorganic pyrophosphatase: structure, thermostability, and effect of metal ion in an archael pyrophosphatase.
Related PDB1qez
Related Swiss-protP50308
[26]
PubMed ID10618499
JournalFEBS Lett
Year1999
Volume464
Pages169-73
AuthorsAvaeva S, Grigorjeva O, Mitkevich V, Sklyankina V, Varfolomeyev S
TitleInteraction of Escherichia coli inorganic pyrophosphatase active sites.
[27]
PubMed ID10739480
JournalBiochemistry (Mosc)
Year2000
Volume65
Pages361-72
AuthorsAvaeva SM
TitleActive site interactions in oligomeric structures of inorganic pyrophosphatases.
[28]
PubMed ID11009607
JournalBiochemistry
Year2000
Volume39
Pages11939-47
AuthorsBaykov AA, Fabrichniy IP, Pohjanjoki P, Zyryanov AB, Lahti R
TitleFluoride effects along the reaction pathway of pyrophosphatase: evidence for a second enzyme.pyrophosphate intermediate.
[29]
Commentscatalysis
PubMed ID11076535
JournalBiochemistry
Year2000
Volume39
Pages13931-8
AuthorsBelogurov GA, Fabrichniy IP, Pohjanjoki P, Kasho VN, Lehtihuhta E, Turkina MV, Cooperman BS, Goldman A, Baykov AA, Lahti R
TitleCatalytically important ionizations along the reaction pathway of yeast pyrophosphatase.
[30]
CommentsX-ray crystallography (1.15/1.9 Angstroms, product complex/fluoride-inhibited complex)
PubMed ID11248042
JournalProc Natl Acad Sci U S A
Year2001
Volume98
Pages3121-6
AuthorsHeikinheimo P, Tuominen V, Ahonen AK, Teplyakov A, Cooperman BS, Baykov AA, Lahti R, Goldman A
TitleToward a quantum-mechanical description of metal-assisted phosphoryl transfer in pyrophosphatase.
Related PDB1e6a,1e9g
[31]
PubMed ID11279052
JournalJ Biol Chem
Year2001
Volume276
Pages17629-34
AuthorsZyryanov AB, Pohjanjoki P, Kasho VN, Shestakov AS, Goldman A, Lahti R, Baykov AA
TitleThe electrophilic and leaving group phosphates in the catalytic mechanism of yeast pyrophosphatase.
[32]
PubMed ID11566028
JournalArch Biochem Biophys
Year2001
Volume394
Pages61-6
AuthorsLopes DH, Sola-Penna M
TitleUrea increases tolerance of yeast inorganic pyrophosphatase activity to ethanol: the other side of urea interaction with proteins.
[33]
PubMed ID11754735
JournalJ Biochem (Tokyo)
Year2002
Volume131
Pages53-8
AuthorsMasuda H, Uchiumi T, Wada M, Ichiba T, Hachimori A
TitleEffects of replacement of prolines with alanines on the catalytic activity and thermostability of inorganic pyrophosphatase from thermophilic bacterium PS-3.
[34]
PubMed ID11846572
JournalJ Mol Biol
Year2001
Volume314
Pages633-45
AuthorsSamygina VR, Popov AN, Rodina EV, Vorobyeva NN, Lamzin VS, Polyakov KM, Kurilova SA, Nazarova TI, Avaeva SM
TitleThe structures of Escherichia coli inorganic pyrophosphatase complexed with Ca(2+) or CaPP(i) at atomic resolution and their mechanistic implications.
[35]
PubMed ID12169093
JournalBiochem J
Year2002
Volume367
Pages901-6
AuthorsZyryanov AB, Shestakov AS, Lahti R, Baykov AA
TitleMechanism by which metal cofactors control substrate specificity in pyrophosphatase.

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

createdupdated
2002-09-042011-02-09


Copyright: Nozomi Nagano, JST & CBRC-AIST
Funded by PRESTO/Japan Science and Technology Corporation (JST) (December 2001 - November 2004)
Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2005 - March 2006)
Funded by Grant-in-Aid for Scientific Research (B)/Japan Society for the Promotion of Science (JSPS) (April 2005 - March 2008)
Funded by BIRD/Japan Science and Technology Corporation (JST) (September 2005 - September 2010)
Funded by BIRD/Japan Science and Technology Corporation (JST) (October 2007 - September 2010)
Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2011 - March 2012)

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