PROSITE

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.

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Technical section

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

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

• Sequences in UniProtKB/Swiss-Prot known to belong to this class: 239
  • detected by PS50035: 229 (true positives)
  • undetected by PS50035: 10 (10 false negatives and 0 'partial')
• Other sequence(s) in UniProtKB/Swiss-Prot detected by PS50035:
  2 false positives.
• Domain architecture view of Swiss-Prot proteins matching PS50035
  
• Retrieve an alignment of UniProtKB/Swiss-Prot true positive hits:
  Clustal format, color, condensed view  /  Clustal format, color  /  Clustal format, plain text  /  Fasta format
• Retrieve the sequence logo from the alignment
• Taxonomic distribution of all UniProtKB (Swiss-Prot + TrEMBL) entries matching PS50035
• Retrieve a list of all UniProtKB (Swiss-Prot + TrEMBL) entries matching PS50035
• Scan UniProtKB (Swiss-Prot and/or TrEMBL) entries against PS50035
• View ligand binding statistics of PS50035
• Matching PDB structures: 1XDO 1XDP 2ZE4 2ZE9 ... [ALL]

References

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).
PubMed ID	8669123

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).
PubMed ID	8732763

3	Authors	Koonin E.V.
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).
PubMed ID	8755242

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).
PubMed ID	10074947
DOI	10.1038/6716

5	Authors	Xie Z. Ho W.-T. Exton J.H.
Title	Association of the N- and C-terminal domains of phospholipase D. 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).
PubMed ID	10825182
DOI	10.1074/jbc.M909745199

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