PDBsum entry 2zkm

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protein metals links
Hydrolase PDB id
Protein chain
708 a.a. *
Waters ×692
* Residue conservation analysis
PDB id:
Name: Hydrolase
Title: Crystal structure of phospholipasE C beta 2
Structure: 1-phosphatidylinositol-4,5-bisphosphate phosphodiesterase beta-2. Chain: x. Fragment: residues 1-799 (ph-c2 domains). Synonym: phosphoinositide phospholipasE C, phospholipasE C- beta-2, plc-beta-2. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: plc beta 2. Expressed in: spodoptera frugiperda. Expression_system_taxid: 7108. Expression_system_cell_line: sf21.
1.62Å     R-factor:   0.197     R-free:   0.213
Authors: S.N.Hicks,M.R.Jezyk,S.Gershberg,J.P.Seifert,T.K.Harden, J.Sondek
Key ref:
S.N.Hicks et al. (2008). General and versatile autoinhibition of PLC isozymes. Mol Cell, 31, 383-394. PubMed id: 18691970 DOI: 10.1016/j.molcel.2008.06.018
26-Mar-08     Release date:   12-Aug-08    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
Q00722  (PLCB2_HUMAN) -  1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2
1185 a.a.
708 a.a.
Protein chain
Pfam   ArchSchema ?
Q59F77  (Q59F77_HUMAN) -  Phosphoinositide phospholipase C (Fragment)
901 a.a.
708 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     4 terms  


DOI no: 10.1016/j.molcel.2008.06.018 Mol Cell 31:383-394 (2008)
PubMed id: 18691970  
General and versatile autoinhibition of PLC isozymes.
S.N.Hicks, M.R.Jezyk, S.Gershburg, J.P.Seifert, T.K.Harden, J.Sondek.
Phospholipase C (PLC) isozymes are directly activated by heterotrimeric G proteins and Ras-like GTPases to hydrolyze phosphatidylinositol 4,5-bisphosphate into the second messengers diacylglycerol and inositol 1,4,5-trisphosphate. Although PLCs play central roles in myriad signaling cascades, the molecular details of their activation remain poorly understood. As described here, the crystal structure of PLC-beta2 illustrates occlusion of the active site by a loop separating the two halves of the catalytic TIM barrel. Removal of this insertion constitutively activates PLC-beta2 without ablating its capacity to be further stimulated by classical G protein modulators. Similar regulation occurs in other PLC members, and a general mechanism of interfacial activation at membranes is presented that provides a unifying framework for PLC activation by diverse stimuli.
  Selected figure(s)  
Figure 1.
Figure 1. Overall Structure of PLC-β2
(A) PLC-β isozymes are composed of an N-terminal pleckstrin homology (PH) domain, an array of EF hands, a catalytic TIM barrel split by a highly degenerate linker sequence (green), a C2 domain, and a C-terminal coiled-coil (CT) domain necessary for homodimerization. Sequence conservation of all human PLCs is graphed (red trace) relative to their shared domain architecture, X and Y regions of high sequence conservation are indicated, and absolute domain borders are listed for human PLC-β2.
(B) The X/Y linker occludes the active site of PLC-β2. The 1.6 Å resolution structure of PLC-β2 is depicted in ribbon form (left panel) with domain boundaries colored as in (A) and the approximate membrane-binding surface at the top. Also shown are the calcium cofactor (yellow sphere) within the active site and the hydrophobic ridge that is a major point of contact with membranes. Surface representation of PLC-β2 (right panel) rotated 90° with respect to the left panel emphasizes the occlusion of the active site within the TIM barrel by the X/Y linker. For reference, superposition of the active site of PLC-δ1 containing IP[3] and PLC-β2 was used to dock IP[3] (purple) into the TIM barrel of PLC-β2.
(C) Superimposition of the crystal structures of the isolated PLC-β2 fragment colored as in (B) and the equivalent fragment from the Rac1-bound form (gray; PDB ID code 2FJU).
Figure 2.
Figure 2. Structural Details of the Active Site of PLC-β2
(A and B) Active site residues in PLC-δ1 that coordinate calcium (yellow) and interact (dashed lines) with IP[3] (purple) are conserved in (B) PLC-β2.
(C) An extended portion of the X/Y linker (green; residues 527–536) participates in a set of H bonds (dashed lines) with active site residues (red) of PLC-β2. The equivalent portion of the linker from the structure of PLC-β2 bound to Rac1 is shown in gray.
(D) Simulated annealing omit map (2F[o] − F[c]; contoured at 1σ) highlighting the density for residues 517–537 of the X/Y linker.
  The above figures are reprinted from an Open Access publication published by Cell Press: Mol Cell (2008, 31, 383-394) copyright 2008.  
  Figures were selected by an automated process.  

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
20870410 T.D.Bunney, and M.Katan (2011).
PLC regulation: emerging pictures for molecular mechanisms.
  Trends Biochem Sci, 36, 88-96.  
20579885 F.Philip, G.Kadamur, R.G.Silos, J.Woodson, and E.M.Ross (2010).
Synergistic activation of phospholipase C-beta3 by Galpha(q) and Gbetagamma describes a simple two-state coincidence detector.
  Curr Biol, 20, 1327-1335.  
20966218 G.L.Waldo, T.K.Ricks, S.N.Hicks, M.L.Cheever, T.Kawano, K.Tsuboi, X.Wang, C.Montell, T.Kozasa, J.Sondek, and T.K.Harden (2010).
Kinetic scaffolding mediated by a phospholipase C-beta and Gq signaling complex.
  Science, 330, 974-980.
PDB code: 3ohm
20573804 J.Kashir, B.Heindryckx, C.Jones, P.De Sutter, J.Parrington, and K.Coward (2010).
Oocyte activation, phospholipase C zeta and human infertility.
  Hum Reprod Update, 16, 690-703.  
20553968 K.Fukami, S.Inanobe, K.Kanemaru, and Y.Nakamura (2010).
Phospholipase C is a key enzyme regulating intracellular calcium and modulating the phosphoinositide balance.
  Prog Lipid Res, 49, 429-437.  
19470488 A.Fujita, J.Cheng, K.Tauchi-Sato, T.Takenawa, and T.Fujimoto (2009).
A distinct pool of phosphatidylinositol 4,5-bisphosphate in caveolae revealed by a nanoscale labeling technique.
  Proc Natl Acad Sci U S A, 106, 9256-9261.  
19531496 K.L.Everett, T.D.Bunney, Y.Yoon, F.Rodrigues-Lima, R.Harris, P.C.Driscoll, K.Abe, H.Fuchs, Angelis, P.Yu, W.Cho, and M.Katan (2009).
Characterization of phospholipase C gamma enzymes with gain-of-function mutations.
  J Biol Chem, 284, 23083-23093.  
  19033212 T.K.Harden, S.N.Hicks, and J.Sondek (2009).
Phospholipase C isozymes as effectors of Ras superfamily GTPases.
  J Lipid Res, 50, S243-S248.  
18765661 J.P.Seifert, Y.Zhou, S.N.Hicks, J.Sondek, and T.K.Harden (2008).
Dual Activation of Phospholipase C-{epsilon} by Rho and Ras GTPases.
  J Biol Chem, 283, 29690-29698.  
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.