PROSITE documentation PDOC50035 [for PROSITE entry PS50035]

Phospholipase D phosphodiesterase active site profile




Description

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.

Technical section

PROSITE method (with tools and information) covered by this documentation:

PLD, PS50035; Phospholipase D phosphodiesterase active site profile  (MATRIX)


References

1AuthorsMorris A.J., Engebrecht J., Frohman M.A.
TitleStructure and regulation of phospholipase D.
SourceTrends Pharmacol. Sci. 17:182-185(1996).
PubMed ID8669123

2AuthorsPonting C.P., Kerr I.D.
TitleA novel family of phospholipase D homologues that includes phospholipid synthases and putative endonucleases: identification of duplicated repeats and potential active site residues.
SourceProtein Sci. 5:914-922(1996).
PubMed ID8732763

3AuthorsKoonin E.V.
TitleA duplicated catalytic motif in a new superfamily of phosphohydrolases and phospholipid synthases that includes poxvirus envelope proteins.
SourceTrends Biochem. Sci. 21:242-243(1996).
PubMed ID8755242

4AuthorsStuckey J.A., Dixon J.E.
TitleCrystal structure of a phospholipase D family member.
SourceNat. Struct. Biol. 6:278-284(1999).
PubMed ID10074947
DOI10.1038/6716

5AuthorsXie Z., Ho W.-T., Exton J.H. Association of the N- and C-terminal domains of phospholipase D.
TitleContribution of the conserved HKD motifs to the interaction and the requirement of the association for Ser/Thr phosphorylation of the enzyme.
SourceJ. Biol. Chem. 275:24962-24969(2000).
PubMed ID10825182
DOI10.1074/jbc.M909745199



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