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Catalytic Site Atlas

CSA LITERATURE entry for 1v0y

E.C. namephospholipase D
SpeciesStreptomyces sp. (Bacteria)
E.C. Number (IntEnz)
CSA Homologues of 1v0yThere are 25 Homologs
CSA Entries With UniProtID
CSA Entries With EC Number
PDBe Entry 1v0y
PDBSum Entry 1v0y
MACiE Entry 1v0y

Literature Report

IntroductionPhospholipase D catalyses the hydrolysis of phospholipids (normally phosphatidyl choline) into phosphatidic acid (PA) and the polar head group (normally choline). The PA generated can be converted into second messengers such as diacylglycerol (DAG) and is also suggested to cause changes in lipid bilayer properties. Phospholipase D will additionally catalyse transphosphatidylation reactions in vitro when an alcohol is present as the nucleophilic donor. It has been shown to be part of a superfamily that includes cardiolipin synthases, phosphatidyl serine synthases, poxvirus envelope proteins and several endonucleases.
MechansimThe catalysed hydrolysis reaction occurs in two steps. First, nucleophilic attack by His 170 on the substrate phosphate leads to displacement of the alcohol head group (e.g. choline if the substrate is phosphatidyl choline) and formation of a His-phosphatidate intermediate with a covalent P-N bond to His 170 N-epsilon. The departing polar head group is protonated by His 448. In the second step, His 448 deprotonates a water molecule that attacks the His-phosphatidate intermediate to displace His 170 and produce phosphatidate. Asp 473 and Asp 202 interact with and modify the pKa values of His 170 and His 448 respectively.

Catalytic Sites for 1v0y

Annotated By Reference To The Literature - Site 1 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
AspA473465macie:sideChainModifies pKa of His 170.
HisA170167macie:sideChainAttacks phosphate of substrate to form a covalent His-Phosphatidate intermediate that is subsequently hydrolysed.
HisA448440macie:sideChainProtonates departing alcohol group (eg choline) during formation of the His-Phosphatidate intermediate. Later deprotonates the water molecule that attacks this intermediate.
AspA202199macie:sideChainModifies pKa of His 448.

Literature References

Leiros I
The reaction mechanism of phospholipase D from Streptomyces sp. strain PMF. Snapshots along the reaction pathway reveal a pentacoordinate reaction intermediate and an unexpected final product.
J Mol Biol 2004 339 805-820
PubMed: 15165852
Gottlin EB
Catalytic mechanism of the phospholipase D superfamily proceeds via a covalent phosphohistidine intermediate.
Proc Natl Acad Sci U S A 1998 95 9202-9207
PubMed: 9689058