PDBsum entry 4k44

Hydrolase

PDB id: 4k44

Contents

Protein chains

104 a.a.

Waters ×103

PDB id:

4k44

Name:

Hydrolase

Title:

Auto-inhibition and phosphorylation-induced activation of plc-gamma isozymes

Structure:

1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1. Chain: a, b. Fragment: c-terminal sh2 (csh2) domain. Synonym: phosphoinositide phospholipasE C-gamma-1, phospholipasE C- gamma-1, plc-gamma-1. Engineered: yes

Source:

Rattus norvegicus. Rat. Organism_taxid: 10116. Gene: plcg1. Expressed in: escherichia coli. Expression_system_taxid: 562

Resolution:

1.70Å R-factor: 0.184 R-free: 0.223

Authors:

N.Hajicek,J.Sondek

Key ref:

N.Hajicek et al. (2013). Autoinhibition and phosphorylation-induced activation of phospholipase C-γ isozymes. Biochemistry, 52, 4810-4819. PubMed id: 23777354 DOI: 10.1021/bi400433b

Date:

11-Apr-13 Release date: 26-Jun-13

Protein chains

P10686  (PLCG1_RAT) -  1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1 from Rattus norvegicus

Seq: 1290 a.a.

Struc: 104 a.a.*

* PDB and UniProt seqs differ at 3 residue positions (black crosses)

Enzyme reactions

• Enzyme class: E.C.3.1.4.11 - phosphoinositide phospholipase C.
• Pathway: myo-Inositol Phosphate Metabolism
• Reaction: a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol-4,5-bisphosphate) + H2O = 1D-myo-inositol 1,4,5-trisphosphate + a 1,2-diacyl-sn-glycerol + H⁺

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

Added reference

DOI no: 10.1021/bi400433b

Biochemistry 52:4810-4819 (2013)

PubMed id: 23777354

Autoinhibition and phosphorylation-induced activation of phospholipase C-γ isozymes.

N.Hajicek, T.H.Charpentier, J.R.Rush, T.K.Harden, J.Sondek.

ABSTRACT

Multiple extracellular stimuli, such as growth factors and antigens, initiate signaling cascades through tyrosine phosphorylation and activation of phospholipase C-γ (PLC-γ) isozymes. Like most other PLCs, PLC-γ1 is basally autoinhibited by its X-Y linker, which separates the X- and Y-boxes of the catalytic core. The C-terminal SH2 (cSH2) domain within the X-Y linker is the critical determinant for autoinhibition of phospholipase activity. Release of autoinhibition requires an intramolecular interaction between the cSH2 domain and a phosphorylated tyrosine, Tyr783, also located within the X-Y linker. The molecular mechanisms that mediate autoinhibition and phosphorylation-induced activation have not been defined. Here, we describe structures of the cSH2 domain both alone and bound to a PLC-γ1 peptide encompassing phosphorylated Tyr783. The cSH2 domain remains largely unaltered by peptide engagement. Point mutations in the cSH2 domain located at the interface with the peptide were sufficient to constitutively activate PLC-γ1, suggesting that peptide engagement directly interferes with the capacity of the cSH2 domain to block the lipase active site. This idea is supported by mutations in a complementary surface of the catalytic core that also enhanced phospholipase activity.