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Catalytic Site Atlas

CSA LITERATURE entry for 2isd

E.C. namephosphoinositide phospholipase C
SpeciesRattus norvegicus (Rat)
E.C. Number (IntEnz) 3.1.4.11
CSA Homologues of 2isdThere are 12 Homologs
CSA Entries With UniProtID P10688
CSA Entries With EC Number 3.1.4.11
PDBe Entry 2isd
PDBSum Entry 2isd
MACiE Entry M0028

Literature Report

IntroductionMammalian 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.
MechansimThe 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.
Reaction

Catalytic Sites for 2isd

Annotated By Reference To The Literature - Site 1 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
HisA356356macie:sideChainActivates water by deprotonation to allow it to act as a nucleophile and hydrolyse the cyclic phosphate intermediate.
HisA311311macie:sideChainForms hydrogen bonds to stabilise the cyclic intermediate structure which then collapses to release the products.
GluA341341macie:sideChainActs 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.

Annotated By Reference To The Literature - Site 2 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
HisB356356macie:sideChainActivates water by deprotonation to allow it to act as a nucleophile and hydrolyse the cyclic phosphate intermediate.
HisB311311macie:sideChainForms hydrogen bonds to stabilise the cyclic intermediate structure which then collapses to release the products.
GluB341341macie:sideChainActs 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.

Literature References

Notes:
Essen LO
Crystal structure of a mammalian phosphoinositide-specific phospholipase C delta.
Nature 1996 380 595-602
PubMed: 8602259
Ellis MV
Catalytic domain of phosphoinositide-specific phospholipase C (PLC). Mutational analysis of residues within the active site and hydrophobic ridge of plcdelta1.
J Biol Chem 1998 273 11650-11659
PubMed: 9565585
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