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PDBsum entry 1djz

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protein ligands metals Protein-protein interface(s) links
Lipid degradation PDB id
1djz
Jmol
Contents
Protein chains
513 a.a. *
561 a.a. *
Ligands
ACT ×2
IP2 ×2
Metals
_CA ×4
Waters ×266
* Residue conservation analysis
PDB id:
1djz
Name: Lipid degradation
Title: Phosphoinositide-specific phospholipasE C-delta1 from rat complexed with inositol-4,5-bisphosphate
Structure: Phosphoinositide-specific phospholipasE C, isozyme delta1. Chain: a, b. Synonym: plc-d1. Engineered: yes. Mutation: yes. Other_details: catalytically-active deletion variant that lacks an n-terminal ph domain, complexed with inositol-4,5- bisphosphate
Source: Rattus norvegicus. Norway rat. Organism_taxid: 10116. Gene: cdna fragment. Expressed in: escherichia coli. Expression_system_taxid: 562.
Resolution:
2.95Å     R-factor:   0.212     R-free:   0.270
Authors: L.-O.Essen,O.Perisic,R.L.Williams
Key ref:
L.O.Essen et al. (1997). Structural mapping of the catalytic mechanism for a mammalian phosphoinositide-specific phospholipase C. Biochemistry, 36, 1704-1718. PubMed id: 9048554 DOI: 10.1021/bi962512p
Date:
24-Aug-96     Release date:   07-Jul-97    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P10688  (PLCD1_RAT) -  1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase delta-1
Seq:
Struc:
 
Seq:
Struc:
756 a.a.
513 a.a.
Protein chain
Pfam   ArchSchema ?
P10688  (PLCD1_RAT) -  1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase delta-1
Seq:
Struc:
 
Seq:
Struc:
756 a.a.
561 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: Chains A, B: E.C.3.1.4.11  - Phosphoinositide phospholipase C.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]

      Pathway:
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
Bound ligand (Het Group name = IP2)
matches with 83.00% similarity
+ 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  

 

 
    reference    
 
 
DOI no: 10.1021/bi962512p Biochemistry 36:1704-1718 (1997)
PubMed id: 9048554  
 
 
Structural mapping of the catalytic mechanism for a mammalian phosphoinositide-specific phospholipase C.
L.O.Essen, O.Perisic, M.Katan, Y.Wu, M.F.Roberts, R.L.Williams.
 
  ABSTRACT  
 
The crystal structures of various ternary complexes of phosphoinositide-specific phospholipase C-delta 1 from rat with calcium and inositol phosphates have been determined at 2.30-2.95 A resolution. The inositol phosphates used in this study mimic the binding of substrates and the reaction intermediate and include D-myo-inositol-1,4,5-trisphosphate, D-myo-inositol-2,4, 5-trisphosphate. D-myo-inositol-4,5-bisphosphate, and D,1-myo-inositol-2-methylene-1,2-cyclićmonophosphonate. The complexes exhibit an almost invariant mode of binding in the active site, each fitting edge-on into the active site and interacting with both the enzyme and the catalytic calcium at the bottom of the active site. Most of the active site residues do not undergo conformational changes upon binding either calcium or inositol phosphates. The structures are consistent with bidentate liganding of the catalytic calcium to the inositol phosphate intermediate and transition state. The complexes suggest explanations for substrate preference, pH optima, and ratio of cyclic to acyclic reaction products. A reaction mechanism is derived that supports general acid/base catalysis in a sequential mechanism involving a cyclic phosphate intermediate and rules out a parallel mechanism where acyclic and cyclic products are simultaneously generated.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
21822282 A.M.Lyon, V.M.Tesmer, V.D.Dhamsania, D.M.Thal, J.Gutierrez, S.Chowdhury, K.C.Suddala, J.K.Northup, and J.J.Tesmer (2011).
An autoinhibitory helix in the C-terminal region of phospholipase C-β mediates Gαq activation.
  Nat Struct Mol Biol, 18, 999.
PDB codes: 3qr0 3qr1
19681039 M.Fujii, K.S.Yi, M.J.Kim, S.H.Ha, S.H.Ryu, P.G.Suh, and H.Yagisawa (2009).
Phosphorylation of phospholipase C-delta 1 regulates its enzymatic activity.
  J Cell Biochem, 108, 638-650.  
18214971 A.S.Ozyurt, and T.L.Selby (2008).
Computational active site analysis of molecular pathways to improve functional classification of enzymes.
  Proteins, 72, 184-196.  
18604568 C.Andreini, I.Bertini, G.Cavallaro, G.L.Holliday, and J.M.Thornton (2008).
Metal ions in biological catalysis: from enzyme databases to general principles.
  J Biol Inorg Chem, 13, 1205-1218.  
  18725531 C.C.Hernandez, O.Zaika, and M.S.Shapiro (2008).
A carboxy-terminal inter-helix linker as the site of phosphatidylinositol 4,5-bisphosphate action on Kv7 (M-type) K+ channels.
  J Gen Physiol, 132, 361-381.  
18691970 S.N.Hicks, M.R.Jezyk, S.Gershburg, J.P.Seifert, T.K.Harden, and J.Sondek (2008).
General and versatile autoinhibition of PLC isozymes.
  Mol Cell, 31, 383-394.
PDB code: 2zkm
17588168 A.Rosenhouse-Dantsker, and D.E.Logothetis (2007).
Molecular characteristics of phosphoinositide binding.
  Pflugers Arch, 455, 45-53.  
17213187 C.Shao, X.Shi, H.Wehbi, C.Zambonelli, J.F.Head, B.A.Seaton, and M.F.Roberts (2007).
Dimer structure of an interfacially impaired phosphatidylinositol-specific phospholipase C.
  J Biol Chem, 282, 9228-9235.
PDB code: 2or2
17524618 G.Drin, and S.Scarlata (2007).
Stimulation of phospholipase Cbeta by membrane interactions, interdomain movement, and G protein binding--how many ways can you activate an enzyme?
  Cell Signal, 19, 1383-1392.  
17659518 Y.Liu, C.Mihai, R.J.Kubiak, M.Rebecchi, and K.S.Bruzik (2007).
Phosphorothiolate analogues of phosphatidylinositols as assay substrates for phospholipase C.
  Chembiochem, 8, 1430-1439.  
16617426 H.Deng, G.Chen, W.Yang, and J.J.Yang (2006).
Predicting calcium-binding sites in proteins - a graph theory and geometry approach.
  Proteins, 64, 34-42.  
17013611 V.Schick, M.Majores, G.Engels, S.Spitoni, A.Koch, C.E.Elger, M.Simon, C.Knobbe, I.Blümcke, and A.J.Becker (2006).
Activation of Akt independent of PTEN and CTMP tumor-suppressor gene mutations in epilepsy-associated Taylor-type focal cortical dysplasias.
  Acta Neuropathol, 112, 715-725.  
16195461 M.Rao, and S.Sockanathan (2005).
Transmembrane protein GDE2 induces motor neuron differentiation in vivo.
  Science, 309, 2212-2215.  
  12807765 C.M.Manning, W.R.Mathews, L.P.Fico, and J.R.Thackeray (2003).
Phospholipase C-gamma contains introns shared by src homology 2 domains in many unrelated proteins.
  Genetics, 164, 433-442.  
12577262 J.B.Mitchell, and J.Smith (2003).
D-amino acid residues in peptides and proteins.
  Proteins, 50, 563-571.  
12598680 R.A.Segal (2003).
Selectivity in neurotrophin signaling: theme and variations.
  Annu Rev Neurosci, 26, 299-330.  
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.  
10779349 H.Lin, J.H.Choi, J.Hasek, N.DeLillo, W.Lou, and A.Vancura (2000).
Phospholipase C is involved in kinetochore function in Saccharomyces cerevisiae.
  Mol Cell Biol, 20, 3597-3607.  
10873862 I.Leiros, F.Secundo, C.Zambonelli, S.Servi, and E.Hough (2000).
The first crystal structure of a phospholipase D.
  Structure, 8, 655-667.
PDB code: 1f0i
9915811 C.Zhou, D.Horstman, G.Carpenter, and M.F.Roberts (1999).
Action of phosphatidylinositol-specific phospholipase Cgamma1 on soluble and micellar substrates. Separating effects on catalysis from modulation of the surface.
  J Biol Chem, 274, 2786-2793.  
10508789 D.E.Timm, H.A.Mueller, P.Bhanumoorthy, J.M.Harp, and G.J.Bunick (1999).
Crystal structure and mechanism of a carbon-carbon bond hydrolase.
  Structure, 7, 1023-1033.
PDB codes: 1qcn 1qco 1qqj
10570253 R.L.Williams (1999).
Mammalian phosphoinositide-specific phospholipase C.
  Biochim Biophys Acta, 1441, 255-267.  
9646876 M.J.Rebecchi, and S.Scarlata (1998).
Pleckstrin homology domains: a common fold with diverse functions.
  Annu Rev Biophys Biomol Struct, 27, 503-528.  
9838022 M.Katan (1998).
Families of phosphoinositide-specific phospholipase C: structure and function.
  Biochim Biophys Acta, 1436, 5.  
9565585 M.V.Ellis, S.R.James, O.Perisic, C.P.Downes, R.L.Williams, and M.Katan (1998).
Catalytic domain of phosphoinositide-specific phospholipase C (PLC). Mutational analysis of residues within the active site and hydrophobic ridge of plcdelta1.
  J Biol Chem, 273, 11650-11659.  
9521777 R.J.Hondal, Z.Zhao, A.V.Kravchuk, H.Liao, S.R.Riddle, X.Yue, K.S.Bruzik, and M.D.Tsai (1998).
Mechanism of phosphatidylinositol-specific phospholipase C: a unified view of the mechanism of catalysis.
  Biochemistry, 37, 4568-4580.  
9871708 S.G.Aneja, P.T.Ivanova, and R.Aneja (1998).
Synthesis of 2-deoxy-2-fluoro-phosphatidylinositol-4,5-bisphosphate and analogues: probes and modulators of the mammalian PI-PLCS.
  Bioorg Med Chem Lett, 8, 1061-1064.  
9335537 C.S.Gässler, M.Ryan, T.Liu, O.H.Griffith, and D.W.Heinz (1997).
Probing the roles of active site residues in phosphatidylinositol-specific phospholipase C from Bacillus cereus by site-directed mutagenesis.
  Biochemistry, 36, 12802-12813.
PDB codes: 2ptd 3ptd 4ptd 5ptd 6ptd 7ptd
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.  
9346303 T.Pawelczyk, and A.Matecki (1997).
Structural requirements of phospholipase C delta1 for regulation by spermine, sphingosine and sphingomyelin.
  Eur J Biochem, 248, 459-465.  
9214296 Y.Wu, and M.F.Roberts (1997).
Phosphatidylinositol-specific phospholipase C cyclic phosphodiesterase activity depends on solvent polarity.
  Biochemistry, 36, 8514-8521.  
9287165 Y.Wu, O.Perisic, R.L.Williams, M.Katan, and M.F.Roberts (1997).
Phosphoinositide-specific phospholipase C delta1 activity toward micellar substrates, inositol 1,2-cyclic phosphate, and other water-soluble substrates: a sequential mechanism and allosteric activation.
  Biochemistry, 36, 11223-11233.  
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 codes are shown on the right.