PDBsum entry: 2zkm

Hydrolase

PDB id: 2zkm

Contents

Protein chain

708 a.a. *

Metals

_CA

Waters ×692

* Residue conservation analysis

PDB id:

2zkm

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.

Resolution:

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

Date:

26-Mar-08 Release date: 12-Aug-08

Protein chain

Q00722  (PLCB2_HUMAN) -  1-phosphatidylinositol-4,5-bisphosphate phosphodiesterase beta-2

Seq: 1185 a.a.

Struc: 708 a.a.

Enzyme reactions

• Enzyme class: E.C.3.1.4.11 - Phosphoinositide phospholipase C.
• Pathway: myo-Inositol Phosphate Metabolism
• Reaction: 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate + H₂O = 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 

• Biological process: lipid metabolic process (2 terms)
• Biochemical function: calcium ion binding (4 terms)

reference

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.

ABSTRACT

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.