{PDOC50035}
{PS50035; PLD}
{BEGIN}
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* Phospholipase D phosphodiesterase active site profile *
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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.

-Sequences known to belong to this class detected by the profile: ALL.
-Other sequence(s) detected in Swiss-Prot: 1, Chlamydomonas reinhardtii dynein
 alpha chain.
-Last update: April 2002 / First entry.

[ 1] Morris A.J., Engebrecht J., Frohman M.A.
     "Structure and regulation of phospholipase D."
     Trends Pharmacol. Sci. 17:182-185(1996).
     PubMed=8669123
[ 2] Ponting C.P., Kerr I.D.
     "A novel family of phospholipase D homologues that includes
     phospholipid synthases and putative endonucleases: identification of
     duplicated repeats and potential active site residues."
     Protein Sci. 5:914-922(1996).
     PubMed=8732763
[ 3] Koonin E.V.
     "A duplicated catalytic motif in a new superfamily of
     phosphohydrolases and phospholipid synthases that includes poxvirus
     envelope proteins."
     Trends Biochem. Sci. 21:242-243(1996).
     PubMed=8755242
[ 4] Stuckey J.A., Dixon J.E.
     "Crystal structure of a phospholipase D family member."
     Nat. Struct. Biol. 6:278-284(1999).
     PubMed=10074947; DOI=10.1038/6716
[ 5] Xie Z., Ho W.-T., Exton J.H.
     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."
     J. Biol. Chem. 275:24962-24969(2000).
     PubMed=10825182; DOI=10.1074/jbc.M909745199

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