|PROSITE documentation PDOC50035 [for PROSITE entry PS50035]|
Phospholipase D (PLD) is an ubiquitous enzyme found in bacteria, fungi, plants and mammals. PLD is involved in vesicle formation, protein transport, signal transduction and mitosis. It catalyzes the breakdown of phosphatidylcholine into choline and the putative second messenger phosphatidic acid, which in turn is broken down into two second messengers (diacylglycerol and lysophosphatidic acid). PLD also catalyzes a phosphatidyl transfer reaction using primary alcohols as nucleophilic acceptors to produce phosphatidylalcohols. Sequence analysis revealed that PLD belongs to a superfamily that includes cardiolipin synthases, phosphatidylserine synthase, poxvirus envelope proteins, a Yersinia murine toxin and several endonucleases.
All members of this superfamily of phosphodiesterases contain the sequence motif H-x-K-x(4)-D-x(6)-G-S-x-N denoted 'HKD'. Despite the distinct substrate specificities of the superfamily members, the consensus HKD motif appears to be essential for their enzymatic activity. Most of the enzymes in the superfamily contain two copies of this consensus sequence, but the bacterial endonuclease contain only a single copy [1,2,3]. Two HKD motifs are supposed to associate to produce a single active site. It has been proposed that upon substrate binding, one of the histidine residues function as the nucleophile attacking the phosphodiester bond, while the other histidine could serve as a general acid protonating the oxygen atom of the leaving group [4,5].
The profile we developed is centered around the phospholipase D phosphodiesterase active site.Last update:
April 2002 / First entry.
PROSITE method (with tools and information) covered by this documentation:
|1||Authors||Morris A.J. Engebrecht J. Frohman M.A.|
|Title||Structure and regulation of phospholipase D.|
|Source||Trends Pharmacol. Sci. 17:182-185(1996).|
|2||Authors||Ponting C.P. Kerr I.D.|
|Title||A novel family of phospholipase D homologues that includes phospholipid synthases and putative endonucleases: identification of duplicated repeats and potential active site residues.|
|Source||Protein Sci. 5:914-922(1996).|
|Title||A duplicated catalytic motif in a new superfamily of phosphohydrolases and phospholipid synthases that includes poxvirus envelope proteins.|
|Source||Trends Biochem. Sci. 21:242-243(1996).|
|4||Authors||Stuckey J.A. Dixon J.E.|
|Title||Crystal structure of a phospholipase D family member.|
|Source||Nat. Struct. Biol. 6:278-284(1999).|
|5||Authors||Xie Z. Ho W.-T. Exton J.H. Association of the N- and C-terminal domains of phospholipase D.|
|Title||Contribution of the conserved HKD motifs to the interaction and the requirement of the association for Ser/Thr phosphorylation of the enzyme.|
|Source||J. Biol. Chem. 275:24962-24969(2000).|