PDBsum entry 1qat

Go to PDB code: 
protein metals Protein-protein interface(s) links
Hydrolase PDB id
Protein chains
509 a.a. *
_SM ×5
* Residue conservation analysis
PDB id:
Name: Hydrolase
Title: 1-phosphatidylinositol-4,5-bisphosphate phosphodiesterase delta complex with samarium (iii) chloride
Structure: PhospholipasE C delta-1. Chain: a, b. Synonym: plc-delta-1. Engineered: yes. Other_details: phoshoinositide-specific phospholipasE C delta-1
Source: Rattus norvegicus. Norway rat. Organism_taxid: 10116. Organ: seed. Expressed in: escherichia coli. Expression_system_taxid: 562.
3.00Å     R-factor:   0.194     R-free:   0.261
Authors: J.A.Grobler,J.H.Hurley
Key ref: J.A.Grobler et al. (1996). C2 domain conformational changes in phospholipase C-delta 1. Nat Struct Biol, 3, 788-795. PubMed id: 8784353
02-Aug-96     Release date:   12-Feb-97    
Go to PROCHECK summary

Protein chains
Pfam   ArchSchema ?
P10688  (PLCD1_RAT) -  1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase delta-1
756 a.a.
509 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.  - Phosphoinositide phospholipase C.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]

myo-Inositol Phosphate Metabolism
      Reaction: 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate + H2O = 1D-myo-inositol 1,4,5-trisphosphate + diacylglycerol
1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate
+ H(2)O
= 1D-myo-inositol 1,4,5-trisphosphate
+ diacylglycerol
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Biological process     intracellular signal transduction   3 terms 
  Biochemical function     calcium ion binding     3 terms  


Nat Struct Biol 3:788-795 (1996)
PubMed id: 8784353  
C2 domain conformational changes in phospholipase C-delta 1.
J.A.Grobler, L.O.Essen, R.L.Williams, J.H.Hurley.
The structure of the PH-domain truncated core of rat phosphoinositide-specific phospholipase C-delta 1 has been determined at 2.4 A resolution and compared to the structure previously determined in a different crystal form. The stereochemical relationship between the EF, catalytic, and C2 domains is essentially identical. The Ca2+ analogue Sm3+ binds at two sites between the jaws of the C2 domain. Sm3+ binding ejects three lysine residues which bridge the gap between the jaws and occupy the Ca2+ site in the apoenzyme, triggering a conformational change in the jaws. The distal sections of the C2 jaws move apart, opening the mouth by 9 A and creating a gap large enough to bind a phospholipid headgroup.

Literature references that cite this PDB file's key reference

  PubMed id Reference
20023071 H.Moreno, A.S.Linford, C.A.Gilchrist, and W.A.Petri (2010).
Phospholipid-binding protein EhC2A mediates calcium-dependent translocation of transcription factor URE3-BP to the plasma membrane of Entamoeba histolytica.
  Eukaryot Cell, 9, 695-704.  
20167601 L.Premkumar, A.A.Bobkov, M.Patel, L.Jaroszewski, L.A.Bankston, B.Stec, K.Vuori, J.F.Côté, and R.C.Liddington (2010).
Structural basis of membrane targeting by the Dock180 family of Rho family guanine exchange factors (Rho-GEFs).
  J Biol Chem, 285, 13211-13222.
PDB code: 3l4c
16616874 J.H.Hurley (2006).
Membrane binding domains.
  Biochim Biophys Acta, 1761, 805-811.  
15735337 T.C.Appleby, G.Larson, I.W.Cheney, H.Walker, J.Z.Wu, W.Zhong, Z.Hong, and N.Yao (2005).
Structure of human uridine-cytidine kinase 2 determined by SIRAS using a rotating-anode X-ray generator and a single samarium derivative.
  Acta Crystallogr D Biol Crystallogr, 61, 278-284.
PDB code: 1xrj
15790568 Z.Kouchi, T.Shikano, Y.Nakamura, H.Shirakawa, K.Fukami, and S.Miyazaki (2005).
The role of EF-hand domains and C2 domain in regulation of enzymatic activity of phospholipase Czeta.
  J Biol Chem, 280, 21015-21021.  
12573692 J.H.Hurley (2003).
Membrane proteins: adapting to life at the interface.
  Chem Biol, 10, 2-3.  
12963743 P.Wang, C.T.Wang, J.Bai, M.B.Jackson, and E.R.Chapman (2003).
Mutations in the effector binding loops in the C2A and C2B domains of synaptotagmin I disrupt exocytosis in a nonadditive manner.
  J Biol Chem, 278, 47030-47037.  
12009889 A.A.Frazier, M.A.Wisner, N.J.Malmberg, K.G.Victor, G.E.Fanucci, E.A.Nalefski, J.J.Falke, and D.S.Cafiso (2002).
Membrane orientation and position of the C2 domain from cPLA2 by site-directed spin labeling.
  Biochemistry, 41, 6282-6292.  
11753430 A.U.Singer, G.L.Waldo, T.K.Harden, and J.Sondek (2002).
A unique fold of phospholipase C-beta mediates dimerization and interaction with G alpha q.
  Nat Struct Biol, 9, 32-36.
PDB code: 1jad
11805296 J.Bai, P.Wang, and E.R.Chapman (2002).
C2A activates a cryptic Ca(2+)-triggered membrane penetration activity within the C2B domain of synaptotagmin I.
  Proc Natl Acad Sci U S A, 99, 1665-1670.  
11912206 J.Feng, H.Wehbi, and M.F.Roberts (2002).
Role of tryptophan residues in interfacial binding of phosphatidylinositol-specific phospholipase C.
  J Biol Chem, 277, 19867-19875.  
11325731 R.Galneder, V.Kahl, A.Arbuzova, M.Rebecchi, J.O.Rädler, and S.McLaughlin (2001).
Microelectrophoresis of a bilayer-coated silica bead in an optical trap: application to enzymology.
  Biophys J, 80, 2298-2309.  
10634937 A.G.Buckland, and D.C.Wilton (2000).
Anionic phospholipids, interfacial binding and the regulation of cell functions.
  Biochim Biophys Acta, 1483, 199-216.  
10940243 J.H.Hurley, and S.Misra (2000).
Signaling and subcellular targeting by membrane-binding domains.
  Annu Rev Biophys Biomol Struct, 29, 49-79.  
11114512 J.H.Hurley, Y.Tsujishita, and M.A.Pearson (2000).
Floundering about at cell membranes: a structural view of phospholipid signaling.
  Curr Opin Struct Biol, 10, 737-743.  
10974000 R.C.Desai, B.Vyas, C.A.Earles, J.T.Littleton, J.A.Kowalchyck, T.F.Martin, and E.R.Chapman (2000).
The C2B domain of synaptotagmin is a Ca(2+)-sensing module essential for exocytosis.
  J Cell Biol, 150, 1125-1136.  
10319815 A.Dessen, J.Tang, H.Schmidt, M.Stahl, J.D.Clark, J.Seehra, and W.S.Somers (1999).
Crystal structure of human cytosolic phospholipase A2 reveals a novel topology and catalytic mechanism.
  Cell, 97, 349-360.
PDB code: 1cjy
10570253 R.L.Williams (1999).
Mammalian phosphoinositide-specific phospholipase C.
  Biochim Biophys Acta, 1441, 255-267.  
10872466 W.F.DeGrado, C.M.Summa, V.Pavone, F.Nastri, and A.Lombardi (1999).
De novo design and structural characterization of proteins and metalloproteins.
  Annu Rev Biochem, 68, 779-819.  
9477951 A.M.Pepio, and W.S.Sossin (1998).
The C2 domain of the Ca(2+)-independent protein kinase C Apl II inhibits phorbol ester binding to the C1 domain in a phosphatidic acid-sensitive manner.
  Biochemistry, 37, 1256-1263.  
9668085 A.M.Pepio, X.Fan, and W.S.Sossin (1998).
The role of C2 domains in Ca2+-activated and Ca2+-independent protein kinase Cs in aplysia.
  J Biol Chem, 273, 19040-19048.  
9668093 B.Davletov, O.Perisic, and R.L.Williams (1998).
Calcium-dependent membrane penetration is a hallmark of the C2 domain of cytosolic phospholipase A2 whereas the C2A domain of synaptotagmin binds membranes electrostatically.
  J Biol Chem, 273, 19093-19096.  
9922129 E.A.Nalefski, and J.J.Falke (1998).
Location of the membrane-docking face on the Ca2+-activated C2 domain of cytosolic phospholipase A2.
  Biochemistry, 37, 17642-17650.  
9430670 E.A.Nalefski, T.McDonagh, W.Somers, J.Seehra, J.J.Falke, and J.D.Clark (1998).
Independent folding and ligand specificity of the C2 calcium-dependent lipid binding domain of cytosolic phospholipase A2.
  J Biol Chem, 273, 1365-1372.  
9593749 E.R.Chapman, and A.F.Davis (1998).
Direct interaction of a Ca2+-binding loop of synaptotagmin with lipid bilayers.
  J Biol Chem, 273, 13995-14001.  
9538021 J.A.Grobler, and J.H.Hurley (1998).
Catalysis by phospholipase C delta1 requires that Ca2+ bind to the catalytic domain, but not the C2 domain.
  Biochemistry, 37, 5020-5028.  
9540160 J.A.Trapani, D.A.Jans, and V.R.Sutton (1998).
Lymphocyte granule-mediated cell death.
  Springer Semin Immunopathol, 19, 323-343.  
9632630 J.Rizo, and T.C.Südhof (1998).
C2-domains, structure and function of a universal Ca2+-binding domain.
  J Biol Chem, 273, 15879-15882.  
9670009 J.Ubach, X.Zhang, X.Shao, T.C.Südhof, and J.Rizo (1998).
Ca2+ binding to synaptotagmin: how many Ca2+ ions bind to the tip of a C2-domain?
  EMBO J, 17, 3921-3930.  
9838094 M.J.Bottomley, K.Salim, and G.Panayotou (1998).
Phospholipid-binding protein domains.
  Biochim Biophys Acta, 1436, 165-183.  
9838022 M.Katan (1998).
Families of phosphoinositide-specific phospholipase C: structure and function.
  Biochim Biophys Acta, 1436, 5.  
9651347 M.Medkova, and W.Cho (1998).
Mutagenesis of the C2 domain of protein kinase C-alpha. Differential roles of Ca2+ ligands and membrane binding residues.
  J Biol Chem, 273, 17544-17552.  
9430701 O.Perisic, S.Fong, D.E.Lynch, M.Bycroft, and R.L.Williams (1998).
Crystal structure of a calcium-phospholipid binding domain from cytosolic phospholipase A2.
  J Biol Chem, 273, 1596-1604.
PDB code: 1rlw
9799511 S.A.Tatulian, J.Steczko, and W.Minor (1998).
Uncovering a calcium-regulated membrane-binding mechanism for soybean lipoxygenase-1.
  Biochemistry, 37, 15481-15490.  
9819203 X.Shao, I.Fernandez, T.C.Südhof, and J.Rizo (1998).
Solution structures of the Ca2+-free and Ca2+-bound C2A domain of synaptotagmin I: does Ca2+ induce a conformational change?
  Biochemistry, 37, 16106-16115.
PDB code: 1byn
9730811 X.Zhang, J.Rizo, and T.C.Südhof (1998).
Mechanism of phospholipid binding by the C2A-domain of synaptotagmin I.
  Biochemistry, 37, 12395-12403.  
9069266 A.C.Newton (1997).
Regulation of protein kinase C.
  Curr Opin Cell Biol, 9, 161-167.  
9340010 E.A.Nalefski, M.M.Slazas, and J.J.Falke (1997).
Ca2+-signaling cycle of a membrane-docking C2 domain.
  Biochemistry, 36, 12011-12018.  
9266179 J.H.Hurley, and J.A.Grobler (1997).
Protein kinase C and phospholipase C: bilayer interactions and regulation.
  Curr Opin Struct Biol, 7, 557-565.  
9325330 L.M.Keranen, and A.C.Newton (1997).
Ca2+ differentially regulates conventional protein kinase Cs' membrane interaction and activation.
  J Biol Chem, 272, 25959-25967.  
9062102 L.O.Essen, O.Perisic, D.E.Lynch, M.Katan, and R.L.Williams (1997).
A ternary metal binding site in the C2 domain of phosphoinositide-specific phospholipase C-delta1.
  Biochemistry, 36, 2753-2762.
PDB codes: 1djg 1djh 1dji
  9253765 M.Mosior, and R.M.Epand (1997).
Protein kinase C: an example of a calcium-regulated protein binding to membranes (review).
  Mol Membr Biol, 14, 65-70.  
9405358 R.Uellner, M.J.Zvelebil, J.Hopkins, J.Jones, L.K.MacDougall, B.P.Morgan, E.Podack, M.D.Waterfield, and G.M.Griffiths (1997).
Perforin is activated by a proteolytic cleavage during biosynthesis which reveals a phospholipid-binding C2 domain.
  EMBO J, 16, 7287-7296.  
9242915 W.D.Singer, H.A.Brown, and P.C.Sternweis (1997).
Regulation of eukaryotic phosphatidylinositol-specific phospholipase C and phospholipase D.
  Annu Rev Biochem, 66, 475-509.  
  8976547 E.A.Nalefski, and J.J.Falke (1996).
The C2 domain calcium-binding motif: structural and functional diversity.
  Protein Sci, 5, 2375-2390.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB code is shown on the right.