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Catalytic Site Atlas Version 2.2.12
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CSA entry for 2isd
Original Entry
Title:
Lipid degradation
Compound:
Phosphoinositide-specific phospholipase c, isozyme delta1
Mutant:
Yes
UniProt/Swiss-Prot:
P10688-PID1_RAT
EC Class:
3.1.4.11
Other CSA Entries:
Overview of all sites for 2isd
Homologues of 2isd
Entries for UniProt/Swiss-Prot: P10688
Entries for EC: 3.1.4.11
Other Databases:
PDB entry: 2isd
PDBsum entry: 2isd
UniProt/Swiss-Prot: P10688
IntEnz entry: 3.1.4.11
Literature Report:
Introduction:
Mammalian phospholipase C catalyses the hydrolysis of Inositol lipid to inositol 1,4,5 trisphosphate and diacyl glycerol, both of which are important second messengers in Ca2+ signalling pathways. It possesses a Triose phosphate isomerase-like catalytic domain, indicating some homology with TIM, but catalyses a different reaction by a mechanism more similar to the T1 RNAases.
Mechanism:
The OH group on C2 acts as a nucleophile, activated by the general base Glu 341, and forms a cyclic phosphate intermediate, with the release of DAG facilitated by the general acid His 356. The intermediate, stabilised by Ca2+ and His 311, is then hydrolysed by a water molecule activated by His 356 to give 1,4,5,inositol trisphosphate and complete the reaction cycle.
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Found by:
Literature reference 

ResidueChainNumberUniProt numberFunctional part FunctionTargetDescription
HISA 311 311Sidechain
ElectrostaticTransition state
Forms hydrogen bonds to stabilise the cyclic intermediate structure which then collapses to release the products.
Evidence from paper Evidence concerns Evidence type
PubMed ID 8602259 Current protein Conservation of residue
PubMed ID 8602259 Current protein Residue is positioned appropriately (ligand position known)
PubMed ID 9565585 Current protein Mutagenesis of residue

ResidueChainNumberUniProt numberFunctional part FunctionTargetDescription
GLUA 341 341Sidechain
Acid/baseSubstrate
Acts as general base to deprotonate the C2 OH of the inositol so that it can act as a nucleophile and attack the phosphate to form the cyclic intermediate, releasing DAG.
Evidence from paper Evidence concerns Evidence type
PubMed ID 9565585 Current protein Residue is positioned appropriately (ligand position known)
PubMed ID 9565585 Current protein Mutagenesis of residue
PubMed ID 9565585 Current protein Conservation of residue

ResidueChainNumberUniProt numberFunctional part FunctionTargetDescription
HISA 356 356Sidechain
Acid/baseWater
Activates water by deprotonation to allow it to act as a nucleophile and hydrolyse the cyclic phosphate intermediate.
Evidence from paper Evidence concerns Evidence type
PubMed ID 9565585 Current protein Residue is positioned appropriately (ligand position known)
PubMed ID 9565585 Current protein Conservation of residue
PubMed ID 9565585 Current protein Mutagenesis of residue
References:
1
Crystal structure of a mammalian phosphoinositide-specific phospholipase C delta.
L. O. Essen and O. Perisic and R. Cheung and M. Katan and R. L. Williams
Nature 380, (6575) 595-602, (1996).
8602259
2
Catalytic domain of phosphoinositide-specific phospholipase C (PLC). Mutational analysis of residues within the active site and hydrophobic ridge of plcdelta1.
M. V. Ellis and S. R. James and O. Perisic and C. P. Downes and R. L. Williams and M. Katan
J Biol Chem 273, (19) 11650-9, (1998).
9565585
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