DB code: M00118

RLCP classification 1.15.72000.565 : Hydrolysis
CATH domain 2.30.29.30 : PH-domain like
1.10.238.10 : Recoverin; domain 1
1.10.238.10 : Recoverin; domain 1
3.20.20.190 : TIM Barrel Catalytic domain
2.60.40.150 : Immunoglobulin-like
E.C. 3.1.4.11
CSA 2isd
M-CSA 2isd
MACiE M0028

CATH domain Related DB codes (homologues)
1.10.238.10 : Recoverin; domain 1 M00183 M00198 D00151
2.30.29.30 : PH-domain like M00125 M00183 M00344
2.60.40.150 : Immunoglobulin-like M00221 M00183 M00043
3.20.20.190 : TIM Barrel M00183 S00236

Uniprot Enzyme Name
UniprotKB Protein name Synonyms RefSeq Pfam
P10688 1-phosphatidylinositol-4,5-bisphosphate phosphodiesterase delta-1
EC 3.1.4.11
Phosphoinositide phospholipase C
Phospholipase C-delta-1
PLC-delta-1
PLC-III
NP_058731.1 (Protein)
NM_017035.1 (DNA/RNA sequence)
PF00168 (C2)
PF09279 (efhand_like)
PF00169 (PH)
PF00388 (PI-PLC-X)
PF00387 (PI-PLC-Y)
[Graphical View]

KEGG enzyme name
phosphoinositide phospholipase C
triphosphoinositide phosphodiesterase
phosphoinositidase C
1-phosphatidylinositol-4,5-bisphosphate phosphodiesterase
monophosphatidylinositol phosphodiesterase
phosphatidylinositol phospholipase C
PI-PLC
1-phosphatidyl-D-myo-inositol-4,5-bisphosphateinositoltrisphosphohydrolase

UniprotKB: Accession Number Entry name Activity Subunit Subcellular location Cofactor
P10688 PLCD1_RAT 1-phosphatidyl-1D-myo-inositol 4,5- bisphosphate + H(2)O = 1D-myo-inositol 1,4,5-trisphosphate + diacylglycerol. Binds 3 calcium ions per subunit. Two of the calcium ions are bound to the C2 domain.

KEGG Pathways
Map code Pathways E.C.
MAP00562 Inositol phosphate metabolism
MAP04070 Phosphatidylinositol signaling system

Compound table
Cofactors Substrates Products Intermediates
KEGG-id C00076 C04637 C00001 C01245 C00165
E.C.
Compound Calcium 1-Phosphatidyl-D-myo-inositol 4,5-bisphosphate H2O D-myo-Inositol 1,4,5-trisphosphate Diacylglycerol
Type divalent metal (Ca2+, Mg2+) carbohydrate,lipid,phosphate group/phosphate ion H2O carbohydrate,phosphate group/phosphate ion carbohydrate,lipid
ChEBI 29108
 29108
 		15377
 15377
 		16595
 16595
PubChem 271
 271
 		22247451
 962
 22247451
 962
 		439456
 439456
1maiA Unbound Unbound Bound:I3P Unbound Unbound
1djgB01 Unbound Unbound Unbound Unbound Unbound
1djhB01 Unbound Unbound Unbound Unbound Unbound
1djiB01 Unbound Unbound Unbound Unbound Unbound
1djwB01 Unbound Unbound Unbound Unbound Unbound
1djxB01 Unbound Unbound Unbound Unbound Unbound
1djyB01 Unbound Unbound Unbound Unbound Unbound
1djzB01 Unbound Unbound Unbound Unbound Unbound
1isdB01 Unbound Unbound Unbound Unbound Unbound
2isdB01 Unbound Unbound Unbound Unbound Unbound
1djgA01 Unbound Unbound Unbound Unbound Unbound
1djgB02 Unbound Unbound Unbound Unbound Unbound
1djhA01 Unbound Unbound Unbound Unbound Unbound
1djhB02 Unbound Unbound Unbound Unbound Unbound
1djiA01 Unbound Unbound Unbound Unbound Unbound
1djiB02 Unbound Unbound Unbound Unbound Unbound
1djwA01 Unbound Unbound Unbound Unbound Unbound
1djwB02 Unbound Unbound Unbound Unbound Unbound
1djxA01 Unbound Unbound Unbound Unbound Unbound
1djxB02 Unbound Unbound Unbound Unbound Unbound
1djyA01 Unbound Unbound Unbound Unbound Unbound
1djyB02 Unbound Unbound Unbound Unbound Unbound
1djzA01 Unbound Unbound Unbound Unbound Unbound
1djzB02 Unbound Unbound Unbound Unbound Unbound
1isdA01 Unbound Unbound Unbound Unbound Unbound
1isdB02 Unbound Unbound Unbound Unbound Unbound
1qasA01 Unbound Unbound Unbound Unbound Unbound
1qasB01 Unbound Unbound Unbound Unbound Unbound
1qatA01 Unbound Unbound Unbound Unbound Unbound
1qatB01 Unbound Unbound Unbound Unbound Unbound
2isdA01 Unbound Unbound Unbound Unbound Unbound
2isdB02 Unbound Unbound Unbound Unbound Unbound
1djgA02 Analogue:_LA Unbound Unbound Unbound Unbound
1djgB03 Analogue:_LA Unbound Unbound Unbound Unbound
1djhA02 Analogue:_BA Unbound Unbound Unbound Unbound
1djhB03 Analogue:_BA Unbound Unbound Unbound Unbound
1djiA02 Bound:_CA Unbound Unbound Unbound Unbound
1djiB03 Bound:_CA Unbound Unbound Unbound Unbound
1djwA02 Bound:_CA Unbound Unbound Unbound Intermediate-analogue:CIP
1djwB03 Bound:_CA Unbound Unbound Unbound Intermediate-analogue:CIP
1djxA02 Bound:_CA Unbound Bound:I3P Unbound Unbound
1djxB03 Bound:_CA Unbound Bound:I3P Unbound Unbound
1djyA02 Bound:_CA Unbound Analogue:I2P Unbound Unbound
1djyB03 Bound:_CA Unbound Analogue:I2P Unbound Unbound
1djzA02 Bound:_CA Unbound Analogue:IP2 Unbound Unbound
1djzB03 Bound:_CA Unbound Analogue:IP2 Unbound Unbound
1isdA02 Unbound Unbound Unbound Unbound Unbound
1isdB03 Unbound Unbound Unbound Unbound Unbound
1qasA02 Unbound Unbound Unbound Unbound Unbound
1qasB02 Unbound Unbound Unbound Unbound Unbound
1qatA02 Analogue:_SM Unbound Unbound Unbound Unbound
1qatB02 Analogue:_SM Unbound Unbound Unbound Unbound
2isdA02 Unbound Unbound Unbound Unbound Unbound
2isdB03 Unbound Unbound Unbound Unbound Unbound
1djgA03 Unbound Unbound Unbound Unbound Unbound
1djgB04 Unbound Unbound Unbound Unbound Unbound
1djhA03 Unbound Unbound Unbound Unbound Unbound
1djhB04 Unbound Unbound Unbound Unbound Unbound
1djiA03 Unbound Unbound Unbound Unbound Unbound
1djiB04 Unbound Unbound Unbound Unbound Unbound
1djwA03 Unbound Unbound Unbound Unbound Unbound
1djwB04 Unbound Unbound Unbound Unbound Unbound
1djxA03 Unbound Unbound Unbound Unbound Unbound
1djxB04 Unbound Unbound Unbound Unbound Unbound
1djyA03 Unbound Unbound Unbound Unbound Unbound
1djyB04 Unbound Unbound Unbound Unbound Unbound
1djzA03 Unbound Unbound Unbound Unbound Unbound
1djzB04 Unbound Unbound Unbound Unbound Unbound
1isdA03 Unbound Unbound Unbound Unbound Unbound
1isdB04 Unbound Unbound Unbound Unbound Unbound
1qasA03 Unbound Unbound Unbound Unbound Unbound
1qasB03 Unbound Unbound Unbound Unbound Unbound
1qatA03 Unbound Unbound Unbound Unbound Unbound
1qatB03 Unbound Unbound Unbound Unbound Unbound
2isdA03 Unbound Unbound Unbound Unbound Unbound
2isdB04 Unbound Unbound Unbound Unbound Unbound

Reference for Active-site residues
resource references E.C.
PDB;1djg, 1djh, 1qat & Swiss-prot;P10688

Active-site residues
PDB Catalytic residues Cofactor-binding residues Modified residues Main-chain involved in catalysis Comment
1maiA
1djgB01
1djhB01
1djiB01
1djwB01
1djxB01
1djyB01
1djzB01
1isdB01
2isdB01
1djgA01
1djgB02
1djhA01
1djhB02
1djiA01
1djiB02
1djwA01
1djwB02
1djxA01
1djxB02
1djyA01
1djyB02
1djzA01
1djzB02
1isdA01
1isdB02
1qasA01
1qasB01
1qatA01
1qatB01
2isdA01
2isdB02
1djgA02 HIS 311;ASN 312;GLU 341;HIS 356;GLU 390 ASN 312;GLU 341;ASP 343;GLU 390(Calcium binding)
1djgB03 HIS 311;ASN 312;GLU 341;HIS 356;GLU 390 ASN 312;GLU 341;ASP 343;GLU 390(Calcium binding)
1djhA02 HIS 311;ASN 312;GLU 341;HIS 356;GLU 390 ASN 312;GLU 341;ASP 343;GLU 390(Calcium binding)
1djhB03 HIS 311;ASN 312;GLU 341;HIS 356;GLU 390 ASN 312;GLU 341;ASP 343;GLU 390(Calcium binding)
1djiA02 HIS 311;ASN 312;GLU 341;HIS 356;GLU 390 ASN 312;GLU 341;ASP 343;GLU 390(Calcium binding)
1djiB03 HIS 311;ASN 312;GLU 341;HIS 356;GLU 390 ASN 312;GLU 341;ASP 343;GLU 390(Calcium binding)
1djwA02 HIS 311;ASN 312;GLU 341;HIS 356;GLU 390 ASN 312;GLU 341;ASP 343;GLU 390(Calcium binding)
1djwB03 HIS 311;ASN 312;GLU 341;HIS 356;GLU 390 ASN 312;GLU 341;ASP 343;GLU 390(Calcium binding)
1djxA02 HIS 311;ASN 312;GLU 341;HIS 356;GLU 390 ASN 312;GLU 341;ASP 343;GLU 390(Calcium binding)
1djxB03 HIS 311;ASN 312;GLU 341;HIS 356;GLU 390 ASN 312;GLU 341;ASP 343;GLU 390(Calcium binding)
1djyA02 HIS 311;ASN 312;GLU 341;HIS 356;GLU 390 ASN 312;GLU 341;ASP 343;GLU 390(Calcium binding)
1djyB03 HIS 311;ASN 312;GLU 341;HIS 356;GLU 390 ASN 312;GLU 341;ASP 343;GLU 390(Calcium binding)
1djzA02 HIS 311;ASN 312;GLU 341;HIS 356;GLU 390 ASN 312;GLU 341;ASP 343;GLU 390(Calcium binding)
1djzB03 HIS 311;ASN 312;GLU 341;HIS 356;GLU 390 ASN 312;GLU 341;ASP 343;GLU 390(Calcium binding)
1isdA02 HIS 311;ASN 312;GLU 341;HIS 356;GLU 390 ASN 312;GLU 341;ASP 343;GLU 390(Calcium binding)
1isdB03 HIS 311;ASN 312;GLU 341;HIS 356;GLU 390 ASN 312;GLU 341;ASP 343;GLU 390(Calcium binding)
1qasA02 HIS 311;ASN 312;GLU 341;HIS 356;GLU 390 ASN 312;GLU 341;ASP 343;GLU 390(Calcium binding)
1qasB02 HIS 311;ASN 312;GLU 341;HIS 356;GLU 390 ASN 312;GLU 341;ASP 343;GLU 390(Calcium binding)
1qatA02 HIS 311;ASN 312;GLU 341;HIS 356;GLU 390 ASN 312;GLU 341;ASP 343;GLU 390(Calcium binding)
1qatB02 HIS 311;ASN 312;GLU 341;HIS 356;GLU 390 ASN 312;GLU 341;ASP 343;GLU 390(Calcium binding)
2isdA02 HIS 311;ASN 312;GLU 341;HIS 356;GLU 390 ASN 312;GLU 341;ASP 343;GLU 390(Calcium binding)
2isdB03 HIS 311;ASN 312;GLU 341;HIS 356;GLU 390 ASN 312;GLU 341;ASP 343;GLU 390(Calcium binding)
1djgA03
1djgB04
1djhA03
1djhB04
1djiA03
1djiB04
1djwA03
1djwB04
1djxA03
1djxB04
1djyA03
1djyB04
1djzA03
1djzB04
1isdA03
1isdB04
1qasA03
1qasB03
1qatA03
1qatB03
2isdA03
2isdB04

References for Catalytic Mechanism
References Sections No. of steps in catalysis
[9]
Fig. 4d, p.600
[12]
Scheme 1A, Fig.9, p.1714-1717
[16]
p.11657-11659
[22]
p.1292-1294

References
[1]
Resource
Comments
Medline ID
PubMed ID 2424507
Journal Biochim Biophys Acta
Year 1986
Volume 864
Pages 123-41
Authors Bernheimer AW, Rudy B
Title Interactions between membranes and cytolytic peptides.
Related PDB
Related UniProtKB
[2]
Resource
Comments
Medline ID
PubMed ID 1497353
Journal Arch Biochem Biophys
Year 1992
Volume 297
Pages 328-33
Authors Pawelczyk T, Lowenstein JM
Title Regulation of phospholipase C delta activity by sphingomyelin and sphingosine.
Related PDB
Related UniProtKB
[3]
Resource
Comments
Medline ID
PubMed ID 7811237
Journal Biochem Biophys Res Commun
Year 1994
Volume 205
Pages 1563-71
Authors Hirata M, Kanematsu T, Sakuma K, Koga T, Watanabe Y, Ozaki S, Yagisawa H
Title D-myo-inositol 1,4,5-trisphosphate binding domain of phospholipase C-delta 1.
Related PDB
Related UniProtKB
[4]
Resource
Comments
Medline ID
PubMed ID 7893146
Journal Arch Biochem Biophys
Year 1995
Volume 317
Pages 331-6
Authors Tsutsumi T, Kobayashi T, Miyashita M, Watanabe S, Homma Y, Okuyama H
Title A lysophosphoinositide-specific phospholipase C distinct from other phospholipase C families in rat brain.
Related PDB
Related UniProtKB
[5]
Resource
Comments
Medline ID
PubMed ID 8554502
Journal Biochem J
Year 1995
Volume 312
Pages 661-6
Authors Paterson HF, Savopoulos JW, Perisic O, Cheung R, Ellis MV, Williams RL, Katan M
Title Phospholipase C delta 1 requires a pleckstrin homology domain for interaction with the plasma membrane.
Related PDB
Related UniProtKB
[6]
Resource
Comments X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 12-130.
Medline ID 96107342
PubMed ID 8521504
Journal Cell
Year 1995
Volume 83
Pages 1037-46
Authors Ferguson KM, Lemmon MA, Schlessinger J, Sigler PB
Title Structure of the high affinity complex of inositol trisphosphate with a phospholipase C pleckstrin homology domain.
Related PDB 1mai
Related UniProtKB P10688
[7]
Resource
Comments
Medline ID
PubMed ID 7479822
Journal Proc Natl Acad Sci U S A
Year 1995
Volume 92
Pages 10472-6
Authors Lemmon MA, Ferguson KM, O'Brien R, Sigler PB, Schlessinger J
Title Specific and high-affinity binding of inositol phosphates to an isolated pleckstrin homology domain.
Related PDB
Related UniProtKB
[8]
Resource
Comments X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 205-756.
Medline ID 96378790
PubMed ID 8784353
Journal Nat Struct Biol
Year 1996
Volume 3
Pages 788-95
Authors Grobler JA, Essen LO, Williams RL, Hurley JH
Title C2 domain conformational changes in phospholipase C-delta 1.
Related PDB
Related UniProtKB P10688
[9]
Resource
Comments X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 133-756.
Medline ID 96186808
PubMed ID 8602259
Journal Nature
Year 1996
Volume 380
Pages 595-602
Authors Essen LO, Perisic O, Cheung R, Katan M, Williams RL
Title Crystal structure of a mammalian phosphoinositide-specific phospholipase C delta.
Related PDB 1isd 2isd
Related UniProtKB P10688
[10]
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
[11]
Resource
Comments
Medline ID
PubMed ID 8810295
Journal J Biol Chem
Year 1996
Volume 271
Pages 25316-26
Authors Lomasney JW, Cheng HF, Wang LP, Kuan Y, Liu S, Fesik SW, King K
Title Phosphatidylinositol 4,5-bisphosphate binding to the pleckstrin homology domain of phospholipase C-delta1 enhances enzyme activity.
Related PDB
Related UniProtKB
[12]
Resource
Comments X-ray crystallography
Medline ID
PubMed ID 9048554
Journal Biochemistry
Year 1997
Volume 36
Pages 1704-18
Authors Essen LO, Perisic O, Katan M, Wu Y, Roberts MF, Williams RL
Title Structural mapping of the catalytic mechanism for a mammalian phosphoinositide-specific phospholipase C.
Related PDB 1djw 1djx 1djy 1djz
Related UniProtKB
[13]
Resource
Comments X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 133-756.
Medline ID 97215812
PubMed ID 9062102
Journal Biochemistry
Year 1997
Volume 36
Pages 2753-62
Authors Essen LO, Perisic O, Lynch DE, Katan M, Williams RL
Title A ternary metal binding site in the C2 domain of phosphoinositide-specific phospholipase C-delta1.
Related PDB 1djg 1djh 1dji
Related UniProtKB P10688
[14]
Resource
Comments
Medline ID
PubMed ID 9405358
Journal EMBO J
Year 1997
Volume 16
Pages 7287-96
Authors Uellner R, Zvelebil MJ, Hopkins J, Jones J, MacDougall LK, Morgan BP, Podack E, Waterfield MD, Griffiths GM
Title Perforin is activated by a proteolytic cleavage during biosynthesis which reveals a phospholipid-binding C2 domain.
Related PDB
Related UniProtKB
[15]
Resource
Comments
Medline ID
PubMed ID 9538021
Journal Biochemistry
Year 1998
Volume 37
Pages 5020-8
Authors Grobler JA, Hurley JH
Title Catalysis by phospholipase C delta1 requires that Ca2+ bind to the catalytic domain, but not the C2 domain.
Related PDB
Related UniProtKB
[16]
Resource
Comments
Medline ID
PubMed ID 9565585
Journal J Biol Chem
Year 1998
Volume 273
Pages 11650-9
Authors Ellis MV, James SR, Perisic O, Downes CP, Williams RL, Katan M
Title Catalytic domain of phosphoinositide-specific phospholipase C (PLC). Mutational analysis of residues within the active site and hydrophobic ridge of plcdelta1.
Related PDB
Related UniProtKB
[17]
Resource
Comments
Medline ID
PubMed ID 9588182
Journal Biochem Biophys Res Commun
Year 1998
Volume 245
Pages 722-8
Authors Shimohama S, Kamiya S, Fujii M, Ogawa T, Kanamori M, Kawamata J, Imura T, Taniguchi T, Yagisawa H
Title Mutation in the pleckstrin homology domain of the human phospholipase C-delta 1 gene is associated with loss of function.
Related PDB
Related UniProtKB
[18]
Resource
Comments
Medline ID
PubMed ID 9707392
Journal Curr Biol
Year 1998
Volume 8
Pages R557-9
Authors Irvine R
Title Inositol phospholipids: translocation, translocation, translocation...
Related PDB
Related UniProtKB
[19]
Resource
Comments
Medline ID
PubMed ID 10453984
Journal Acta Biochim Pol
Year 1999
Volume 46
Pages 91-8
Authors Pawelczyk T
Title Isozymes delta of phosphoinositide-specific phospholipase C.
Related PDB
Related UniProtKB
[20]
Resource
Comments
Medline ID
PubMed ID 10917660
Journal Biochem Soc Trans
Year 1999
Volume 27
Pages 652-7
Authors Yagisawa H, Fujii M, Hirata M
Title Phospholipase C-delta and related molecules.
Related PDB
Related UniProtKB
[21]
Resource
Comments
Medline ID
PubMed ID 9931017
Journal Biochemistry
Year 1999
Volume 38
Pages 1517-24
Authors Wang T, Pentyala S, Rebecchi MJ, Scarlata S
Title Differential association of the pleckstrin homology domains of phospholipases C-beta 1, C-beta 2, and C-delta 1 with lipid bilayers and the beta gamma subunits of heterotrimeric G proteins.
Related PDB
Related UniProtKB
[22]
Resource
Comments
Medline ID
PubMed ID 11015615
Journal Physiol Rev
Year 2000
Volume 80
Pages 1291-335
Authors Rebecchi MJ, Pentyala SN
Title Structure, function, and control of phosphoinositide-specific phospholipase C.
Related PDB
Related UniProtKB
[23]
Resource
Comments
Medline ID
PubMed ID 11867528
Journal EMBO J
Year 2002
Volume 21
Pages 1004-11
Authors Kanematsu T, Jang IS, Yamaguchi T, Nagahama H, Yoshimura K, Hidaka K, Matsuda M, Takeuchi H, Misumi Y, Nakayama K, Yamamoto T, Akaike N, Hirata M, Nakayama K
Title Role of the PLC-related, catalytically inactive protein p130 in GABA(A) receptor function.
Related PDB
Related UniProtKB
[24]
Resource
Comments
Medline ID
PubMed ID 11706040
Journal J Biol Chem
Year 2002
Volume 277
Pages 3568-75
Authors Ananthanarayanan B, Das S, Rhee SG, Murray D, Cho W
Title Membrane targeting of C2 domains of phospholipase C-delta isoforms.
Related PDB
Related UniProtKB
[25]
Resource
Comments
Medline ID
PubMed ID 12401198
Journal FEBS Lett
Year 2002
Volume 531
Pages 28-32
Authors Philip F, Guo Y, Scarlata S
Title Multiple roles of pleckstrin homology domains in phospholipase Cbeta function.
Related PDB
Related UniProtKB
[26]
Resource
Comments
Medline ID
PubMed ID 12019260
Journal J Biol Chem
Year 2002
Volume 277
Pages 27412-22
Authors Varnai P, Lin X, Lee SB, Tuymetova G, Bondeva T, Spat A, Rhee SG, Hajnoczky G, Balla T
Title Inositol lipid binding and membrane localization of isolated pleckstrin homology (PH) domains. Studies on the PH domains of phospholipase C delta 1 and p130.
Related PDB
Related UniProtKB
[27]
Resource
Comments
Medline ID
PubMed ID 12735994
Journal Bioorg Med Chem
Year 2003
Volume 11
Pages 2471-5
Authors Liu Y, Bruzik KS, Ananthanarayanan B, Cho W
Title New aspects of formation of 1,2-cyclic phosphates by phospholipase C-delta1.
Related PDB
Related UniProtKB
[28]
Resource
Comments
Medline ID
PubMed ID 12900402
Journal J Biol Chem
Year 2003
Volume 278
Pages 41253-8
Authors Wing MR, Snyder JT, Sondek J, Harden TK
Title Direct activation of phospholipase C-epsilon by Rho.
Related PDB
Related UniProtKB
[29]
Resource
Comments
Medline ID
PubMed ID 12708849
Journal J Am Chem Soc
Year 2003
Volume 125
Pages 5000-4
Authors Sugimoto K, Mori Y, Makino K, Ohkubo K, Morii T
Title Functional reassembly of a split PH domain.
Related PDB
Related UniProtKB
[30]
Resource
Comments
Medline ID
PubMed ID 12761218
Journal J Biol Chem
Year 2003
Volume 278
Pages 29995-30004
Authors Guo Y, Philip F, Scarlata S
Title The Pleckstrin homology domains of phospholipases C-beta and -delta confer activation through a common site.
Related PDB
Related UniProtKB
[31]
Resource
Comments
Medline ID
PubMed ID 12736268
Journal J Biol Chem
Year 2003
Volume 278
Pages 28019-25
Authors Tuzi S, Uekama N, Okada M, Yamaguchi S, Saito H, Yagisawa H
Title Structure and dynamics of the phospholipase C-delta1 pleckstrin homology domain located at the lipid bilayer surface.
Related PDB
Related UniProtKB
[32]
Resource
Comments
Medline ID
PubMed ID 15182194
Journal Biochemistry
Year 2004
Volume 43
Pages 7522-33
Authors Kobayashi M, Mutharasan RK, Feng J, Roberts MF, Lomasney JW
Title Identification of hydrophobic interactions between proteins and lipids: free fatty acids activate phospholipase C delta1 via allosterism.
Related PDB
Related UniProtKB

Comments
This enzyme is composed of the N-terminal Pleckstrin homology (PH) domain, two EF-hand domains, Catalytic domain, and the C-terminal C2 domain.
The PH domain (PDB;1mai) seems to be important for membrane association (see [5] & [6]).
Although literature [9] & [22] mentioned that calcium ion might activate the 2-hydroxyl group for nucleophilic attack on phosphoryl group, by lowering its pKa, it is against other paper (literature of [6] for BamHI, S00384 in EzCatDB).. According to the literature [12], the ion may play a dual role, (1) stablization of the negative charge on the deprotonated 2-hydroxyl group, and (2) stabilization of the transition state.
Based on the literature [9], [12], [16] & [22], the catalytic reaction proceeds as follows:
(1) Glu341, which is bound to the calcium ion, acts as a general base to deprotonate and activate the 2-hydroxyl group of substrate, 1-Phosphatidyl-D-myo-inositol 4,5-bisphosphate (IP2) (see [16]). This activation is assisted by the calcium ion, which stabilizes the negative charge on the 2-hydroxyl group, and His311, Asn312 & Glu390, which stabilize the negative charge on the phosphate group (see [12]).
(2) The activated 2-hydroxyl group makes a nucleophilic attack on phosphodiester, to form an intermediate, cyclic IP3.
(3) His356 acts as a general acid to protonate the leaving diacylglycerole (DAG).
(4) His356, now, acts as a general base to deprotonate a water molecule.
(5) The activated water makes an attack on the phosphate group of the intermediate. Here, the leaving 2-hydroxyl group is stabilized by the calcium ion, and probably protonated by a general acid, Glu341. This hydrolysis might be facilitated by the conformational strain of the intermediate (see [12]).

Created Updated
2005-04-14 2009-02-26