DB code: S00236

RLCP classification 3.100.790.76 : Transfer
CATH domain 3.20.20.190 : TIM Barrel Catalytic domain
E.C. 4.6.1.13
CSA 2plc
M-CSA 2plc
MACiE M0026

CATH domain Related DB codes (homologues)
3.20.20.190 : TIM Barrel M00183 M00118

Uniprot Enzyme Name
UniprotKB Protein name Synonyms RefSeq Pfam
P34024 1-phosphatidylinositol phosphodiesterase
EC 4.6.1.13
Phosphatidylinositol diacylglycerol-lyase
Phosphatidylinositol-specific phospholipase C
PI-PLC
NP_463732.1 (Protein)
NC_003210.1 (DNA/RNA sequence)
PF00388 (PI-PLC-X)
[Graphical View]
P14262 1-phosphatidylinositol phosphodiesterase
EC 4.6.1.13
Phosphatidylinositol diacylglycerol-lyase
Phosphatidylinositol-specific phospholipase C
PI-PLC
PF00388 (PI-PLC-X)
[Graphical View]
P08954 1-phosphatidylinositol phosphodiesterase
EC 4.6.1.13
Phosphatidylinositol diacylglycerol-lyase
Phosphatidylinositol-specific phospholipase C
PI-PLC
PF00388 (PI-PLC-X)
[Graphical View]

KEGG enzyme name
phosphatidylinositol 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)

UniprotKB: Accession Number Entry name Activity Subunit Subcellular location Cofactor
P34024 PLC_LISMO 1-phosphatidyl-1D-myo-inositol = 1D-myo- inositol 1,2-cyclic phosphate + 1,2-diacyl-sn-glycerol. Monomer. Secreted. Cytoplasm. Note=Secreted and, to a lesser extent, cytoplasmic.
P14262 PLC_BACCE 1-phosphatidyl-1D-myo-inositol = 1D-myo- inositol 1,2-cyclic phosphate + 1,2-diacyl-sn-glycerol. Secreted.
P08954 PLC_BACTU 1-phosphatidyl-1D-myo-inositol = 1D-myo- inositol 1,2-cyclic phosphate + 1,2-diacyl-sn-glycerol. Secreted.

KEGG Pathways
Map code Pathways E.C.
MAP00562 Inositol phosphate metabolism

Compound table
Substrates Products Intermediates
KEGG-id C01194 C04299 C00165
E.C.
Compound 1-Phosphatidyl-D-myo-inositol D-myo-Inositol 1,2-cyclic phosphate Diacylglycerol
Type carbohydrate,lipid,phosphate group/phosphate ion carbohydrate,phosphate group/phosphate ion carbohydrate,lipid
ChEBI 18426
PubChem 122331
1aodA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Analogue:INS Unbound
2plcA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound
1gymA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Analogue:MYG Unbound Unbound
1ptdA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound
1ptgA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Analogue:INS Unbound
2ptdA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound
3ptdA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound
4ptdA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound
5ptdA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound
6ptdA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound
7ptdA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound
1t6mA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound
1t6mB Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound
2or2A Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound
2or2B Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound

Reference for Active-site residues
resource references E.C.
literature [18], [24], [25], [26], [28], [29], [32], [34] & Catalytic Site Atlas (2plc)

Active-site residues
PDB Catalytic residues Cofactor-binding residues Modified residues Main-chain involved in catalysis Comment
1aodA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain HIS 45;ASP 46;ARG 84;HIS 93;ASP 278
2plcA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain HIS 45;ASP 46;ARG 84;HIS 93;ASP 278
1gymA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain HIS 32;ASP 33;ARG 69;HIS 82;ASP 274
1ptdA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain HIS 32;ASP 33;ARG 69;HIS 82;ASP 274
1ptgA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain HIS 32;ASP 33;ARG 69;HIS 82;ASP 274
2ptdA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain HIS 32;ASP 33;ARG 69;HIS 82;ASP 274
3ptdA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain HIS 32;ASP 33;ARG 69;HIS 82; mutant D274S
4ptdA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain HIS 32;ASP 33;ARG 69;HIS 82; mutant D274N
5ptdA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ;ASP 33;ARG 69;HIS 82;ASP 274 mutant H32A
6ptdA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ;ASP 33;ARG 69;HIS 82;ASP 274 mutant H32L
7ptdA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain HIS 32;ASP 33;ARG 69;HIS 82;ASP 274 mutant R163K
1t6mA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain HIS 36;ASP 37; ;HIS 86;ASP 278 mutant R73D
1t6mB Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain HIS 36;ASP 37; ;HIS 86;ASP 278 mutant R73D
2or2A Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain HIS 32;ASP 33;ARG 69;HIS 82;ASP 274
2or2B Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain HIS 32;ASP 33;ARG 69;HIS 82;ASP 274

References for Catalytic Mechanism
References Sections No. of steps in catalysis
[1]
Scheme III, Scheme IV, p.2755 1
[4]
p.5189-5192
[5]
Scheme VIII, p.5191 2
[10]
Fig. 8, p.3860 4
[12]
p.9502
[14]
Fig. 1
[16]
p.1391
[17]
Fig.8, p.12810-12812 2
[18]
Fig.1, p.6641 2
[22]
Fig. 1, p.277-278 2
[23]
Fig. 1, p.1940-1943 2
[24]
Fig. 1, Fig. 2, Fig. 9, p.4577-4578
[25]
Fig. 7, p.644-645
[26]
Fig. 7, p.245-249 2
[28]
Scheme I, Fig. 1, Fig. 4, p.5428-5431 2
[29]
Fig. 5, Fig. 6, p.9749-9750 2
[32]
Fig. 1, Fig. 2, p.2426-2429 2
[34]
Fig. 7, p.3242
[35]
Scheme 1, p.9984-9988

References
[1]
Resource
Comments
Medline ID
PubMed ID 2161255
Journal Biochemistry
Year 1990
Volume 29
Pages 2747-57
Authors Lin GL, Bennett CF, Tsai MD
Title Phospholipids chiral at phosphorus. Stereochemical mechanism of reactions catalyzed by phosphatidylinositide-specific phospholipase C from Bacillus cereus and guinea pig uterus.
Related PDB
Related UniProtKB
[2]
Resource
Comments
Medline ID
PubMed ID 2160965
Journal J Biol Chem
Year 1990
Volume 265
Pages 9201-7
Authors Chien MM, Cambier JC
Title Divalent cation regulation of phosphoinositide metabolism. Naturally occurring B lymphoblasts contain a Mg2(+)-regulated phosphatidylinositol-specific phospholipase C.
Related PDB
Related UniProtKB
[3]
Resource
Comments
Medline ID
PubMed ID 1814635
Journal Chem Phys Lipids
Year 1991
Volume 60
Pages 101-10
Authors Shashidhar MS, Volwerk JJ, Griffith OH, Keana JF
Title A chromogenic substrate for phosphatidylinositol-specific phospholipase C: 4-nitrophenyl myo-inositol-1-phosphate.
Related PDB
Related UniProtKB
[4]
Resource
Comments
Medline ID
PubMed ID 1646930
Journal Methods Enzymol
Year 1991
Volume 197
Pages 258-69
Authors Bruzik KS, Tsai MD
Title Phospholipase stereospecificity at phosphorus.
Related PDB
Related UniProtKB
[5]
Resource
Comments
Medline ID
PubMed ID 1318746
Journal Biochemistry
Year 1992
Volume 31
Pages 5183-93
Authors Bruzik KS, Morocho AM, Jhon DY, Rhee SG, Tsai MD
Title Phospholipids chiral at phosphorus. Stereochemical mechanism for the formation of inositol 1-phosphate catalyzed by phosphatidylinositol-specific phospholipase C.
Related PDB
Related UniProtKB
[6]
Resource
Comments
Medline ID
PubMed ID 8395883
Journal Biochemistry
Year 1993
Volume 32
Pages 8836-41
Authors Lewis KA, Garigapati VR, Zhou C, Roberts MF
Title Substrate requirements of bacterial phosphatidylinositol-specific phospholipase C.
Related PDB
Related UniProtKB
[7]
Resource
Comments
Medline ID
PubMed ID 8386017
Journal Biophys J
Year 1993
Volume 64
Pages 784-91
Authors Bullock TL, Ryan M, Kim SL, Remington SJ, Griffith OH
Title Crystallization of phosphatidylinositol-specific phospholipase C from Bacillus cereus.
Related PDB
Related UniProtKB
[8]
Resource
Comments
Medline ID
PubMed ID 8142343
Journal Biochemistry
Year 1994
Volume 33
Pages 3464-74
Authors Volwerk JJ, Filthuth E, Griffith OH, Jain MK
Title Phosphatidylinositol-specific phospholipase C from Bacillus cereus at the lipid-water interface: interfacial binding, catalysis, and activation.
Related PDB
Related UniProtKB
[9]
Resource
Comments
Medline ID
PubMed ID 7531435
Journal Biochem J
Year 1995
Volume 305
Pages 745-51
Authors Koblan KS, Schaber MD, Edwards G, Gibbs JB, Pompliano DL
Title src-homology 2 (SH2) domain ligation as an allosteric regulator: modulation of phosphoinositide-specific phospholipase C gamma 1 structure and activity.
Related PDB
Related UniProtKB
[10]
Resource
Comments X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS).
Medline ID 95393962
PubMed ID 7664726
Journal EMBO J
Year 1995
Volume 14
Pages 3855-63
Authors Heinz DW, Ryan M, Bullock TL, Griffith OH
Title Crystal structure of the phosphatidylinositol-specific phospholipase C from Bacillus cereus in complex with myo-inositol.
Related PDB 1ptd 1ptg
Related UniProtKB P14262
[11]
Resource
Comments
Medline ID
PubMed ID 8869740
Journal Adv Enzyme Regul
Year 1996
Volume 36
Pages 57-71
Authors Roberts MF, Wu Y, Zhou C, Geng D, Tan C
Title Mechanism and structure based inhibitors of phospholipase C enzymes.
Related PDB
Related UniProtKB
[12]
Resource
Comments X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS).
Medline ID 96302248
PubMed ID 8755729
Journal Biochemistry
Year 1996
Volume 35
Pages 9496-504
Authors Heinz DW, Ryan M, Smith MP, Weaver LH, Keana JF, Griffith OH
Title Crystal 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 PDB 1gym
Related UniProtKB P14262
[13]
Resource
Comments
Medline ID
PubMed ID 8893831
Journal J Med Chem
Year 1996
Volume 39
Pages 4366-76
Authors Ryan M, Smith MP, Vinod TK, Lau WL, Keana JF, Griffith OH
Title Synthesis, structure-activity relationships, and the effect of polyethylene glycol on inhibitors of phosphatidylinositol-specific phospholipase C from Bacillus cereus.
Related PDB
Related UniProtKB
[14]
Resource
Comments
Medline ID
PubMed ID 8877813
Journal J Mol Recognit
Year 1996
Volume 9
Pages 197-209
Authors Vizitiu D, Kriste AG, Campbell AS, Thatcher GR
Title Inhibition of phosphatidylinositol-specific phospholipase C: studies on synthetic substrates, inhibitors and a synthetic enzyme.
Related PDB
Related UniProtKB
[15]
Resource
Comments
Medline ID
PubMed ID 8602254
Journal Nature
Year 1996
Volume 380
Pages 581-3
Authors Irvine R
Title Phospholipid signalling. Taking stock of PI-PLC.
Related PDB
Related UniProtKB
[16]
Resource
Comments
Medline ID
PubMed ID 8994965
Journal Structure
Year 1996
Volume 4
Pages 1387-94
Authors Williams RL, Katan M
Title Structural views of phosphoinositide-specific phospholipase C: signalling the way ahead.
Related PDB
Related UniProtKB
[17]
Resource
Comments X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS).
Medline ID 97477327
PubMed ID 9335537
Journal Biochemistry
Year 1997
Volume 36
Pages 12802-13
Authors Gassler CS, Ryan M, Liu T, Griffith OH, Heinz DW
Title Probing the roles of active site residues in phosphatidylinositol-specific phospholipase C from Bacillus cereus by site-directed mutagenesis.
Related PDB 2ptd 3ptd 4ptd 5ptd 6ptd 7ptd
Related UniProtKB P14262
[18]
Resource
Comments
Medline ID
PubMed ID 9184143
Journal Biochemistry
Year 1997
Volume 36
Pages 6633-42
Authors Hondal RJ, Riddle SR, Kravchuk AV, Zhao Z, Liao H, Bruzik KS, Tsai MD
Title Phosphatidylinositol-specific phospholipase C: kinetic and stereochemical evidence for an interaction between arginine-69 and the phosphate group of phosphatidylinositol.
Related PDB
Related UniProtKB
[19]
Resource
Comments
Medline ID
PubMed ID 9398326
Journal Biochemistry
Year 1997
Volume 36
Pages 15925-31
Authors Zhou C, Garigapati V, Roberts MF
Title Short-chain phosphatidylinositol conformation and its relevance to phosphatidylinositol-specific phospholipase C.
Related PDB
Related UniProtKB
[20]
Resource
Comments
Medline ID
PubMed ID 9254604
Journal Biochemistry
Year 1997
Volume 36
Pages 10089-97
Authors Zhou C, Qian X, Roberts MF
Title Allosteric activation of phosphatidylinositol-specific phospholipase C: specific phospholipid binding anchors the enzyme to the interface.
Related PDB
Related UniProtKB
[21]
Resource
Comments
Medline ID
PubMed ID 9003187
Journal Biochemistry
Year 1997
Volume 36
Pages 347-55
Authors Zhou C, Wu Y, Roberts MF
Title Activation of phosphatidylinositol-specific phospholipase C toward inositol 1,2-(cyclic)-phosphate.
Related PDB
Related UniProtKB
[22]
Resource
Comments X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 43-317.
Medline ID 98035056
PubMed ID 9367761
Journal J Mol Biol
Year 1997
Volume 273
Pages 269-82
Authors Moser J, Gerstel B, Meyer JE, Chakraborty T, Wehland J, Heinz DW
Title Crystal structure of the phosphatidylinositol-specific phospholipase C from the human pathogen Listeria monocytogenes.
Related PDB 1aod 2plc
Related UniProtKB P34024
[23]
Resource
Comments
Medline ID
PubMed ID 9300493
Journal Protein Sci
Year 1997
Volume 6
Pages 1937-44
Authors Liu T, Ryan M, Dahlquist FW, Griffith OH
Title Determination of pKa values of the histidine side chains of phosphatidylinositol-specific phospholipase C from Bacillus cereus by NMR spectroscopy and site-directed mutagenesis.
Related PDB
Related UniProtKB
[24]
Resource
Comments
Medline ID
PubMed ID 9521777
Journal Biochemistry
Year 1998
Volume 37
Pages 4568-80
Authors Hondal RJ, Zhao Z, Kravchuk AV, Liao H, Riddle SR, Yue X, Bruzik KS, Tsai MD
Title Mechanism of phosphatidylinositol-specific phospholipase C: a unified view of the mechanism of catalysis.
Related PDB
Related UniProtKB
[25]
Resource
Comments
Medline ID
PubMed ID 9466937
Journal J Mol Biol
Year 1998
Volume 275
Pages 635-50
Authors Heinz DW, Essen LO, Williams RL
Title Structural and mechanistic comparison of prokaryotic and eukaryotic phosphoinositide-specific phospholipases C.
Related PDB
Related UniProtKB
[26]
Resource
Comments
Medline ID
PubMed ID 10570252
Journal Biochim Biophys Acta
Year 1999
Volume 1441
Pages 237-54
Authors Griffith OH, Ryan M
Title Bacterial phosphatidylinositol-specific phospholipase C: structure, function, and interaction with lipids.
Related PDB
Related UniProtKB
[27]
Resource
Comments
Medline ID
PubMed ID 9864213
Journal Infect Immun
Year 1999
Volume 67
Pages 182-6
Authors Bannam T, Goldfine H
Title Mutagenesis of active-site histidines of Listeria monocytogenes phosphatidylinositol-specific phospholipase C: effects on enzyme activity and biological function.
Related PDB
Related UniProtKB
[28]
Resource
Comments
Medline ID
PubMed ID 11331006
Journal Biochemistry
Year 2001
Volume 40
Pages 5422-32
Authors Kubiak RJ, Yue X, Hondal RJ, Mihai C, Tsai MD, Bruzik KS
Title Involvement of the Arg-Asp-His catalytic triad in enzymatic cleavage of the phosphodiester bond.
Related PDB
Related UniProtKB
[29]
Resource
Comments
Medline ID
PubMed ID 11583175
Journal Biochemistry
Year 2001
Volume 40
Pages 9743-50
Authors Ryan M, Liu T, Dahlquist FW, Griffith OH
Title A catalytic diad involved in substrate-assisted catalysis: NMR study of hydrogen bonding and dynamics at the active site of phosphatidylinositol-specific phospholipase C.
Related PDB
Related UniProtKB
[30]
Resource
Comments
Medline ID
PubMed ID 11377433
Journal FEBS Lett
Year 2001
Volume 497
Pages 165-70
Authors Otterhag L, Sommarin M, Pical C
Title N-terminal EF-hand-like domain is required for phosphoinositide-specific phospholipase C activity in Arabidopsis thaliana.
Related PDB
Related UniProtKB
[31]
Resource
Comments
Medline ID
PubMed ID 11912206
Journal J Biol Chem
Year 2002
Volume 277
Pages 19867-75
Authors Feng J, Wehbi H, Roberts MF
Title Role of tryptophan residues in interfacial binding of phosphatidylinositol-specific phospholipase C.
Related PDB
Related UniProtKB
[32]
Resource
Comments
Medline ID
PubMed ID 12600209
Journal Biochemistry
Year 2003
Volume 42
Pages 2422-30
Authors Kravchuk AV, Zhao L, Bruzik KS, Tsai MD
Title Engineering a catalytic metal binding site into a calcium-independent phosphatidylinositol-specific phospholipase C leads to enhanced stereoselectivity.
Related PDB
Related UniProtKB
[33]
Resource
Comments
Medline ID
PubMed ID 12832083
Journal Biochim Biophys Acta
Year 2003
Volume 1613
Pages 15-27
Authors Wehbi H, Feng J, Roberts MF
Title Water-miscible organic cosolvents enhance phosphatidylinositol-specific phospholipase C phosphotransferase as well as phosphodiesterase activity.
Related PDB
Related UniProtKB
[34]
Resource
Comments
Medline ID
PubMed ID 12630878
Journal J Am Chem Soc
Year 2003
Volume 125
Pages 3236-42
Authors Mihai C, Kravchuk AV, Tsai MD, Bruzik KS
Title Application of Bronsted-type LFER in the study of the phospholipase C mechanism.
Related PDB
Related UniProtKB
[35]
Resource
Comments
Medline ID
PubMed ID 16042375
Journal Biochemistry
Year 2005
Volume 44
Pages 9980-9
Authors Apiyo D, Zhao L, Tsai MD, Selby TL
Title X-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.
Related PDB
Related UniProtKB
[36]
Resource
Comments
Medline ID
PubMed ID 17213187
Journal J Biol Chem
Year 2007
Volume 282
Pages 9228-35
Authors Shao C, Shi X, Wehbi H, Zambonelli C, Head JF, Seaton BA, Roberts MF
Title Dimer structure of an interfacially impaired phosphatidylinositol-specific phospholipase C.
Related PDB
Related UniProtKB

Comments
(1) Asp274 modulates the activity of a general base, His32.
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:
(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.

Created Updated
2004-06-23 2009-02-26