PDBsum entry 4qj4

Signaling protein/hydrolase

PDB id: 4qj4

Contents

Protein chains

318 a.a.

749 a.a.

Ligands

GDP-ALF

I3P

Metals

_MG

_CA

Waters ×12

PDB id:

4qj4

Name:

Signaling protein/hydrolase

Title:

Structure of a fragment of human phospholipasE C-beta3 delta472-569, bound to ip3 and in complex with galphaq

Structure:

Guanine nucleotide-binding protein g(q) subunit alpha. Chain: a. Fragment: unp residues 7-359. Synonym: guanine nucleotide-binding protein alpha-q. Engineered: yes. 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3. Chain: b. Fragment: unp residues 10-891.

Source:

Mus musculus. Mouse. Organism_taxid: 10090. Gene: gnaq. Expressed in: trichoplusia ni. Expression_system_taxid: 7111. Homo sapiens. Human. Organism_taxid: 9606.

Resolution:

3.30Å R-factor: 0.211 R-free: 0.267

Authors:

A.M.Lyon,J.J.G.Tesmer

Key ref:

A.M.Lyon et al. (2014). Molecular mechanisms of phospholipase C β3 autoinhibition. Structure, 22, 1844-1854. PubMed id: 25435326 DOI: 10.1016/j.str.2014.10.008

Date:

03-Jun-14 Release date: 22-Oct-14

Protein chain

P21279  (GNAQ_MOUSE) -  Guanine nucleotide-binding protein G(q) subunit alpha from Mus musculus

Seq: 359 a.a.

Struc: 318 a.a.

Protein chain

Q01970  (PLCB3_HUMAN) -  1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 from Homo sapiens

Seq: 1234 a.a.

Struc: 749 a.a.

Enzyme reactions

• Enzyme class: Chain B: 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⁺

1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol-4,5-bisphosphate) + H2O = 1D-myo-inositol 1,4,5-trisphosphate (Bound ligand (Het Group name = I3P) corresponds exactly) + 1,2-diacyl-sn-glycerol + H(+)

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

Added reference

DOI no: 10.1016/j.str.2014.10.008

Structure 22:1844-1854 (2014)

PubMed id: 25435326

Molecular mechanisms of phospholipase C β3 autoinhibition.

A.M.Lyon, J.A.Begley, T.D.Manett, J.J.Tesmer.

ABSTRACT

Phospholipase C β (PLCβ) enzymes are dramatically activated by heterotrimeric G proteins. Central to this response is the robust autoinhibition of PLCβ by the X-Y linker region within its catalytic core and by the Hα2' helix in the C-terminal extension of the enzyme. The molecular mechanism of each and their mutual dependence are poorly understood. Herein, it is shown that distinct regions within the X-Y linker have specific roles in regulating activity. Most important,an acidic stretch within the linker stabilizes a lid that occludes the active site, consistent with crystal structures of variants lacking this region. Inhibition by the Hα2' helix is independent of the X-Y linker and likely regulates activity by limiting membrane interaction of the catalytic core. Full activation of PLCβ thus requires multiple independent molecular events induced by membrane association of the catalytic core and by the binding of regulatory proteins.