Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P00750 (PLA)
 16,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Phospholipase A(1) activities have been detected in most cells where they have been sought and yet their characterization lags far behind that of the phospholipases A(2), C and D. The study presented here details the first cloning and characterization of a cytosolic PLA(1) that exhibits preference for phosphatidylcholine (GPCho) substrates. Trypanosoma brucei phospholipase A(1) (TbPLA(1)) is unique from previously identified eukaryotic PLA(1) because it is evolutionarily related to bacterial secreted PLA(1). A T. brucei ancestor most likely acquired the PLA(1) from a horizontal gene transfer of a PLA(1) from Sodalis glossinidius, a bacterial endosymbiont of tsetse flies. Nano-electrospray ionization tandem mass spectrometry analysis of TbPLA(1) mutants established that the enzyme functions in vivo to synthesize lysoGPCho metabolites containing long-chain mostly polyunsaturated and highly unsaturated fatty acids. Analysis of purified mutated recombinant forms of TbPLA(1) revealed that this enzyme is a serine hydrolase whose catalytic mechanism involves a triad consisting of the amino acid residues Ser-131, His-234 and Asp-183. The TbPLA(1) homozygous null mutants generated here constitute the only PLA(1) double knockouts from any organism.
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PMID:A novel phospholipase from Trypanosoma brucei. 1723 18

Lipoprotein-associated phospholipase A(2) (Lp-PLA(2) or PLA(2)G7) binds to low-density lipoprotein (LDL) particles, where it is thought to hydrolyze oxidatively truncated phospholipids. Lp-PLA(2) has also been implicated as a pro-tumorigenic enzyme in human prostate cancer. Several inhibitors of Lp-PLA(2) have been described, including darapladib, which is currently in phase 3 clinical development for the treatment of atherosclerosis. The selectivity that darapladib and other Lp-PLA(2) inhibitors display across the larger serine hydrolase family has not, however, been reported. Here, we describe the use of both general and tailored activity-based probes for profiling Lp-PLA(2) and inhibitors of this enzyme in native biological systems. We show that both darapladib and a novel class of structurally distinct carbamate inhibitors inactivate Lp-PLA(2) in mouse tissues and human cell lines with high selectivity. Our findings thus identify both inhibitors and chemoproteomic probes that are suitable for investigating Lp-PLA(2) function in biological systems.
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PMID:Selective inhibitors and tailored activity probes for lipoprotein-associated phospholipase A(2). 2326 Mar 46