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 18426
PubChem							122331 122331
1aodA						Unbound	Analogue:INS	Unbound
2plcA						Unbound	Unbound	Unbound
1gymA						Analogue:MYG	Unbound	Unbound
1ptdA						Unbound	Unbound	Unbound
1ptgA						Unbound	Analogue:INS	Unbound
2ptdA						Unbound	Unbound	Unbound
3ptdA						Unbound	Unbound	Unbound
4ptdA						Unbound	Unbound	Unbound
5ptdA						Unbound	Unbound	Unbound
6ptdA						Unbound	Unbound	Unbound
7ptdA						Unbound	Unbound	Unbound
1t6mA						Unbound	Unbound	Unbound
1t6mB						Unbound	Unbound	Unbound
2or2A						Unbound	Unbound	Unbound
2or2B						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						HIS 45;ASP 46;ARG 84;HIS 93;ASP 278
2plcA						HIS 45;ASP 46;ARG 84;HIS 93;ASP 278
1gymA						HIS 32;ASP 33;ARG 69;HIS 82;ASP 274
1ptdA						HIS 32;ASP 33;ARG 69;HIS 82;ASP 274
1ptgA						HIS 32;ASP 33;ARG 69;HIS 82;ASP 274
2ptdA						HIS 32;ASP 33;ARG 69;HIS 82;ASP 274
3ptdA						HIS 32;ASP 33;ARG 69;HIS 82;				mutant D274S
4ptdA						HIS 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
7ptdA						HIS 32;ASP 33;ARG 69;HIS 82;ASP 274				mutant R163K
1t6mA						HIS 36;ASP 37; ;HIS 86;ASP 278				mutant R73D
1t6mB						HIS 36;ASP 37; ;HIS 86;ASP 278				mutant R73D
2or2A						HIS 32;ASP 33;ARG 69;HIS 82;ASP 274
2or2B						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

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.

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