spacer
View the latest EBI news stories and important announcements...
more

spacer
Search The CSA
PDB ID
UNIPROT ID
EC Number

Catalytic Site Atlas

CSA LITERATURE entry for 1bwp

E.C. name1-alkyl-2-acetylglycerophosphocholine esterase
SpeciesBos taurus (Bovine)
E.C. Number (IntEnz) 3.1.1.47
CSA Homologues of 1bwpThere are 24 Homologs
CSA Entries With UniProtID Q29460
CSA Entries With EC Number 3.1.1.47
PDBe Entry 1bwp
PDBSum Entry 1bwp
MACiE Entry M0094

Literature Report

Introduction2-acetyl-1-alkylglycerophosphocholine esterase, also known as known as platelet-activating factor acetylhydrolase (PAF-AH).
Mammalian brain contains significant levels of platelet activating-factor (PAF), these act as a synapse messenger and transcription inducer of the early response genes c-fos and c-jun. The platelet-activating factor PAF is a potent lipid first messenger active in general cell activation, fertilisation, inflammatory and allergic reactions, asthma, HIV pathogenesis, carcinogenesis, and apoptosis. PAF has also been implicated as a messenger in long-term potentiation, a cellular model of memory formation.
Inactivation of this factor is carried out by PAF-AH, a subfamily of phospholipases A2 that remove the sn-2 acetyl group. Mammalian brain contains at least three intracellular isoforms, 1b being the best characterised. From experimentation it can be assumed that PAF-AH maintains the PAF concentration within a certain range during brain development.
The protein is an unusual G-protein like (alpha1/alpha2)beta trimer. PAF-AH is a heterotrimer composed of 26-,26-, and 45-Kda polypeptides. The alpha (26KDa) is the catalytic subunit. The active site is made up of a trypsin-like triad of Ser 47, His 195 and Asp 192. The other subunit is not essential for the catalytic activity. The catalytic subunit contains a single alpha/beta domain with a central, parallel, 6-stranded beta sheet. This fold is very like that found in GTPase. Experimental data has demonstrated that the catalytic subunit of brain PAF acetylhydrolase is a novel type of serine esterase.
MechansimSerine 47 has been identified as the putative nucleophile
SER 47 is close to HIS 195, the imidazole ring of HIS 195 is hydrogen-bonded through its nitrogen (delta 1) atom to the side-chain carboxyl of ASP 192. The chirality of the triad is the same as that found in the active sites of other esterases and neutral lipases, where nucleophilic attack is on the re face of the ester.
Mainchain NH of GLY74 and Nd1 of Asn104 stabilise oxyanion hole.
Reaction

Catalytic Sites for 1bwp

Annotated By Reference To The Literature - Site 1 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
AspA192192macie:sideChain
AsnA104104macie:sideChain
SerA4747macie:sideChain
HisA195195macie:sideChain
GlyA7474macie:mainChainAmide

Literature References

Notes:
Hattori M
The catalytic subunit of bovine brain platelet-activating factor acetylhydrolase is a novel type of serine esterase.
J Biol Chem 1994 269 23150-23155
PubMed: 8083218
Ho YS
Probing the substrate specificity of the intracellular brain platelet-activating factor acetylhydrolase.
Protein Eng 1999 12 693-700
PubMed: 10469831
Ho YS
Brain acetylhydrolase that inactivates platelet-activating factor is a G-protein-like trimer.
Nature 1997 385 89-93
PubMed: 8985254
spacer
spacer