EzCatDB: S00236

DB codeS00236
RLCP classification3.100.790.76
CATH domainDomain 13.20.20.190Catalytic domain
E.C.4.6.1.13
CSA2plc
MACiEM0026

CATH domainRelated DB codes (homologues)
3.20.20.190M00183,M00118

Enzyme Name
Swiss-protKEGG

P34024P14262P08954
Protein name1-phosphatidylinositol phosphodiesterase1-phosphatidylinositol phosphodiesterase1-phosphatidylinositol phosphodiesterasephosphatidylinositol diacylglycerol-lyase
monophosphatidylinositol phosphodiesterase
phosphatidylinositol phospholipase C
1-phosphatidylinositol phosphodiesterase
1-phosphatidyl-D-myo-inositol inositolphosphohydrolase(cyclic-phosphate-forming)
1-phosphatidyl-1D-myo-inositol diacylglycerol-lyase(1,2-cyclic-phosphate-forming)
SynonymsEC 4.6.1.13
Phosphatidylinositol diacylglycerol-lyase
Phosphatidylinositol-specific phospholipase C
PI-PLC
EC 4.6.1.13
Phosphatidylinositol diacylglycerol-lyase
Phosphatidylinositol-specific phospholipase C
PI-PLC
EC 4.6.1.13
Phosphatidylinositol diacylglycerol-lyase
Phosphatidylinositol-specific phospholipase C
PI-PLC

KEGG pathways
MAP codePathways
MAP00562Inositol phosphate metabolism

Swiss-prot:Accession NumberP34024P14262P08954
Entry namePLC_LISMOPLC_BACCEPLC_BACTU
Activity1-phosphatidyl-1D-myo-inositol = 1D-myo- inositol 1,2-cyclic phosphate + 1,2-diacyl-sn-glycerol.1-phosphatidyl-1D-myo-inositol = 1D-myo- inositol 1,2-cyclic phosphate + 1,2-diacyl-sn-glycerol.1-phosphatidyl-1D-myo-inositol = 1D-myo- inositol 1,2-cyclic phosphate + 1,2-diacyl-sn-glycerol.
SubunitMonomer.

Subcellular locationSecreted. Cytoplasm. Note=Secreted and, to a lesser extent, cytoplasmic.Secreted.Secreted.
Cofactor




SubstratesProducts
KEGG-idC01194C04299C00165
Compound1-Phosphatidyl-D-myo-inositolD-myo-Inositol 1,2-cyclic phosphateDiacylglycerol
Typecarbohydrate,lipid,phosphate group/phosphate ioncarbohydrate,phosphate group/phosphate ioncarbohydrate,lipid
1aodAUnboundAnalogue:INSUnbound
2plcAUnboundUnboundUnbound
1gymAAnalogue:MYGUnboundUnbound
1ptdAUnboundUnboundUnbound
1ptgAUnboundAnalogue:INSUnbound
2ptdAUnboundUnboundUnbound
3ptdAUnboundUnboundUnbound
4ptdAUnboundUnboundUnbound
5ptdAUnboundUnboundUnbound
6ptdAUnboundUnboundUnbound
7ptdAUnboundUnboundUnbound
1t6mAUnboundUnboundUnbound
1t6mBUnboundUnboundUnbound
2or2AUnboundUnboundUnbound
2or2BUnboundUnboundUnbound

Active-site residues
resource
literature [18], [24], [25], [26], [28], [29], [32], [34] & Catalytic Site Atlas (2plc)
pdbCatalytic residuescomment
1aodAHIS 45;ASP 46;ARG 84;HIS 93;ASP 278

2plcAHIS 45;ASP 46;ARG 84;HIS 93;ASP 278

1gymAHIS 32;ASP 33;ARG 69;HIS 82;ASP 274

1ptdAHIS 32;ASP 33;ARG 69;HIS 82;ASP 274

1ptgAHIS 32;ASP 33;ARG 69;HIS 82;ASP 274

2ptdAHIS 32;ASP 33;ARG 69;HIS 82;ASP 274

3ptdAHIS 32;ASP 33;ARG 69;HIS 82;       
mutant D274S
4ptdAHIS 32;ASP 33;ARG 69;HIS 82;       
mutant D274N
5ptdA      ;ASP 33;ARG 69;HIS 82;ASP 274
mutant H32A
6ptdA      ;ASP 33;ARG 69;HIS 82;ASP 274
mutant H32L
7ptdAHIS 32;ASP 33;ARG 69;HIS 82;ASP 274
mutant R163K
1t6mAHIS 36;ASP 37;      ;HIS 86;ASP 278
mutant R73D
1t6mBHIS 36;ASP 37;      ;HIS 86;ASP 278
mutant R73D
2or2AHIS 32;ASP 33;ARG 69;HIS 82;ASP 274

2or2BHIS 32;ASP 33;ARG 69;HIS 82;ASP 274


References for Catalytic Mechanism
ReferencesSectionsNo. of steps in catalysis
[1]Scheme III, Scheme IV, p.27551
[4]p.5189-5192
[5]Scheme VIII, p.51912
[10]Fig. 8, p.38604
[12]p.9502
[14]Fig. 1
[16]p.1391
[17]Fig.8, p.12810-128122
[18]Fig.1, p.66412
[22]Fig. 1, p.277-2782
[23]Fig. 1, p.1940-19432
[24]Fig. 1, Fig. 2, Fig. 9, p.4577-4578
[25]Fig. 7, p.644-645
[26]Fig. 7, p.245-2492
[28]Scheme I, Fig. 1, Fig. 4, p.5428-54312
[29]Fig. 5, Fig. 6, p.9749-97502
[32]Fig. 1, Fig. 2, p.2426-24292
[34]Fig. 7, p.3242
[35]Scheme 1, p.9984-9988

references
[1]
PubMed ID2161255
JournalBiochemistry
Year1990
Volume29
Pages2747-57
AuthorsLin GL, Bennett CF, Tsai MD
TitlePhospholipids chiral at phosphorus. Stereochemical mechanism of reactions catalyzed by phosphatidylinositide-specific phospholipase C from Bacillus cereus and guinea pig uterus.
[2]
PubMed ID2160965
JournalJ Biol Chem
Year1990
Volume265
Pages9201-7
AuthorsChien MM, Cambier JC
TitleDivalent cation regulation of phosphoinositide metabolism. Naturally occurring B lymphoblasts contain a Mg2(+)-regulated phosphatidylinositol-specific phospholipase C.
[3]
PubMed ID1814635
JournalChem Phys Lipids
Year1991
Volume60
Pages101-10
AuthorsShashidhar MS, Volwerk JJ, Griffith OH, Keana JF
TitleA chromogenic substrate for phosphatidylinositol-specific phospholipase C: 4-nitrophenyl myo-inositol-1-phosphate.
[4]
PubMed ID1646930
JournalMethods Enzymol
Year1991
Volume197
Pages258-69
AuthorsBruzik KS, Tsai MD
TitlePhospholipase stereospecificity at phosphorus.
[5]
PubMed ID1318746
JournalBiochemistry
Year1992
Volume31
Pages5183-93
AuthorsBruzik KS, Morocho AM, Jhon DY, Rhee SG, Tsai MD
TitlePhospholipids chiral at phosphorus. Stereochemical mechanism for the formation of inositol 1-phosphate catalyzed by phosphatidylinositol-specific phospholipase C.
[6]
PubMed ID8395883
JournalBiochemistry
Year1993
Volume32
Pages8836-41
AuthorsLewis KA, Garigapati VR, Zhou C, Roberts MF
TitleSubstrate requirements of bacterial phosphatidylinositol-specific phospholipase C.
[7]
PubMed ID8386017
JournalBiophys J
Year1993
Volume64
Pages784-91
AuthorsBullock TL, Ryan M, Kim SL, Remington SJ, Griffith OH
TitleCrystallization of phosphatidylinositol-specific phospholipase C from Bacillus cereus.
[8]
PubMed ID8142343
JournalBiochemistry
Year1994
Volume33
Pages3464-74
AuthorsVolwerk JJ, Filthuth E, Griffith OH, Jain MK
TitlePhosphatidylinositol-specific phospholipase C from Bacillus cereus at the lipid-water interface: interfacial binding, catalysis, and activation.
[9]
PubMed ID7531435
JournalBiochem J
Year1995
Volume305
Pages745-51
AuthorsKoblan KS, Schaber MD, Edwards G, Gibbs JB, Pompliano DL
Titlesrc-homology 2 (SH2) domain ligation as an allosteric regulator: modulation of phosphoinositide-specific phospholipase C gamma 1 structure and activity.
[10]
CommentsX-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS).
Medline ID95393962
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JournalEMBO J
Year1995
Volume14
Pages3855-63
AuthorsHeinz DW, Ryan M, Bullock TL, Griffith OH
TitleCrystal structure of the phosphatidylinositol-specific phospholipase C from Bacillus cereus in complex with myo-inositol.
Related PDB1ptd,1ptg
Related Swiss-protP14262
[11]
PubMed ID8869740
JournalAdv Enzyme Regul
Year1996
Volume36
Pages57-71
AuthorsRoberts MF, Wu Y, Zhou C, Geng D, Tan C
TitleMechanism and structure based inhibitors of phospholipase C enzymes.
[12]
CommentsX-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS).
Medline ID96302248
PubMed ID8755729
JournalBiochemistry
Year1996
Volume35
Pages9496-504
AuthorsHeinz DW, Ryan M, Smith MP, Weaver LH, Keana JF, Griffith OH
TitleCrystal structure of phosphatidylinositol-specific phospholipase C from Bacillus cereus in complex with glucosaminyl(alpha 1-->6)-D-myo-inositol, an essential fragment of GPI anchors.
Related PDB1gym
Related Swiss-protP14262
[13]
PubMed ID8893831
JournalJ Med Chem
Year1996
Volume39
Pages4366-76
AuthorsRyan M, Smith MP, Vinod TK, Lau WL, Keana JF, Griffith OH
TitleSynthesis, structure-activity relationships, and the effect of polyethylene glycol on inhibitors of phosphatidylinositol-specific phospholipase C from Bacillus cereus.
[14]
PubMed ID8877813
JournalJ Mol Recognit
Year1996
Volume9
Pages197-209
AuthorsVizitiu D, Kriste AG, Campbell AS, Thatcher GR
TitleInhibition of phosphatidylinositol-specific phospholipase C: studies on synthetic substrates, inhibitors and a synthetic enzyme.
[15]
PubMed ID8602254
JournalNature
Year1996
Volume380
Pages581-3
AuthorsIrvine R
TitlePhospholipid signalling. Taking stock of PI-PLC.
[16]
PubMed ID8994965
JournalStructure
Year1996
Volume4
Pages1387-94
AuthorsWilliams RL, Katan M
TitleStructural views of phosphoinositide-specific phospholipase C: signalling the way ahead.
[17]
CommentsX-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS).
Medline ID97477327
PubMed ID9335537
JournalBiochemistry
Year1997
Volume36
Pages12802-13
AuthorsGassler CS, Ryan M, Liu T, Griffith OH, Heinz DW
TitleProbing the roles of active site residues in phosphatidylinositol-specific phospholipase C from Bacillus cereus by site-directed mutagenesis.
Related PDB2ptd,3ptd,4ptd,5ptd,6ptd,7ptd
Related Swiss-protP14262
[18]
PubMed ID9184143
JournalBiochemistry
Year1997
Volume36
Pages6633-42
AuthorsHondal RJ, Riddle SR, Kravchuk AV, Zhao Z, Liao H, Bruzik KS, Tsai MD
TitlePhosphatidylinositol-specific phospholipase C: kinetic and stereochemical evidence for an interaction between arginine-69 and the phosphate group of phosphatidylinositol.
[19]
PubMed ID9398326
JournalBiochemistry
Year1997
Volume36
Pages15925-31
AuthorsZhou C, Garigapati V, Roberts MF
TitleShort-chain phosphatidylinositol conformation and its relevance to phosphatidylinositol-specific phospholipase C.
[20]
PubMed ID9254604
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Year1997
Volume36
Pages10089-97
AuthorsZhou C, Qian X, Roberts MF
TitleAllosteric activation of phosphatidylinositol-specific phospholipase C: specific phospholipid binding anchors the enzyme to the interface.
[21]
PubMed ID9003187
JournalBiochemistry
Year1997
Volume36
Pages347-55
AuthorsZhou C, Wu Y, Roberts MF
TitleActivation of phosphatidylinositol-specific phospholipase C toward inositol 1,2-(cyclic)-phosphate.
[22]
CommentsX-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 43-317.
Medline ID98035056
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Year1997
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TitleCrystal structure of the phosphatidylinositol-specific phospholipase C from the human pathogen Listeria monocytogenes.
Related PDB1aod,2plc
Related Swiss-protP34024
[23]
PubMed ID9300493
JournalProtein Sci
Year1997
Volume6
Pages1937-44
AuthorsLiu T, Ryan M, Dahlquist FW, Griffith OH
TitleDetermination of pKa values of the histidine side chains of phosphatidylinositol-specific phospholipase C from Bacillus cereus by NMR spectroscopy and site-directed mutagenesis.
[24]
PubMed ID9521777
JournalBiochemistry
Year1998
Volume37
Pages4568-80
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[25]
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Year1998
Volume275
Pages635-50
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Year1999
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Year1999
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TitleMutagenesis of active-site histidines of Listeria monocytogenes phosphatidylinositol-specific phospholipase C: effects on enzyme activity and biological function.
[28]
PubMed ID11331006
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Year2001
Volume40
Pages5422-32
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[29]
PubMed ID11583175
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Year2001
Volume40
Pages9743-50
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TitleA catalytic diad involved in substrate-assisted catalysis: NMR study of hydrogen bonding and dynamics at the active site of phosphatidylinositol-specific phospholipase C.
[30]
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JournalFEBS Lett
Year2001
Volume497
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TitleN-terminal EF-hand-like domain is required for phosphoinositide-specific phospholipase C activity in Arabidopsis thaliana.
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Year2002
Volume277
Pages19867-75
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TitleRole of tryptophan residues in interfacial binding of phosphatidylinositol-specific phospholipase C.
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Year2003
Volume42
Pages2422-30
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TitleEngineering a catalytic metal binding site into a calcium-independent phosphatidylinositol-specific phospholipase C leads to enhanced stereoselectivity.
[33]
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Year2003
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Pages15-27
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[34]
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Year2003
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[35]
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Year2005
Volume44
Pages9980-9
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TitleX-ray structure of the R69D phosphatidylinositol-specific phospholipase C enzyme: insight into the role of calcium and surrounding amino acids in active site geometry and catalysis.
[36]
PubMed ID17213187
JournalJ Biol Chem
Year2007
Volume282
Pages9228-35
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TitleDimer structure of an interfacially impaired phosphatidylinositol-specific phospholipase C.

comments
This enzyme was transferred from E.C. 3.1.4.10 to 4.6.1.13.
This enzyme catalyzes the following reactions:
(A) Intramolecular phosphotransfer reaction:
(B) Hydrolysis:
However, the activity of hydrolysis reaction is very low, according to the literature [25], [26].
The first reaction of this enzyme proceeds as follows:
(1) Asp274 modulates the activity of a general base, His32.
(2) His32 acts as a general base to deprotonate and activate 2-OH group of 1-Phosphatidyl-D-myo-inositol.
(3) The activated hydroxyl group makes a nucleophilic attack on the phosphate group of the substrate, forming a pentacovalent transition state.
(4) The negatively charged transition-state is stabilized by Arg69, which is modulated and oriented by Asp33.
(5) Asp33 also modulates the activity of the general acid, His82.
(6) His32 acts as a general acid to protonate the leaving group, completing the reaction.

createdupdated
2004-06-232009-02-26


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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