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)

The bacterial tripeptide formyl-Met-Leu-Phe (fMLP) induces the secretion of enzyme(s) with phospholipase A(2) (PLA(2)) activity from human neutrophils. We show that circulating human neutrophils express groups V and X sPLA(2) (GV and GX sPLA(2)) mRNA and contain GV and GX sPLA(2) proteins, whereas GIB, GIIA, GIID, GIIE, GIIF, GIII, and GXII sPLA(2)s are undetectable. GV sPLA(2) is a component of both azurophilic and specific granules, whereas GX sPLA(2) is confined to azurophilic granules. Exposure to fMLP or opsonized zymosan results in the release of GV but not GX sPLA(2) and most, if not all, of the PLA(2) activity in the extracellular fluid of fMLP-stimulated neutrophils is due to GV sPLA(2). GV sPLA(2) does not contribute to fMLP-stimulated leukotriene B(4) production but may support the anti-bacterial properties of the neutrophil, because 10-100 ng per ml concentrations of this enzyme lead to Gram-negative bacterial membrane phospholipid hydrolysis in the presence of human serum. By use of a recently described and specific inhibitor of cytosolic PLA(2)-alpha (group IV PLA(2)alpha), we show that this enzyme produces virtually all of the arachidonic acid used for the biosynthesis of leukotriene B(4) in fMLP- and opsonized zymosan-stimulated neutrophils, the major eicosanoid produced by these pro-inflammatory cells.
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PMID:Groups IV, V, and X phospholipases A2s in human neutrophils: role in eicosanoid production and gram-negative bacterial phospholipid hydrolysis. 1174 84

Secreted phospholipases A(2) (sPLA(2) s) are lipolytic enzymes present in organisms ranging from prokaryotes to eukaryotes but their origin and emergence are poorly understood. We identified and compared the conserved domains of 333 sPLA(2) s and proposed a model for their evolution. The conserved domains were grouped into seven categories according to the in silico annotated conserved domain collections of 'cd00618: PLA(2) _like' and 'pfam00068: Phospholip_A2_1'. PLA(2) s containing the conserved domain cd04706 (plant-specific PLA(2) ) are present in bacteria and plants. Metazoan PLA(2) s of the group (G) I/II/V/X PLA(2) collection exclusively contain the conserved domain cd00125. GIII PLA(2) s of both vertebrates and invertebrates contain the conserved domain cd04704 (bee venom-like PLA(2) ), and mammalian GIII PLA(2) s also contain the conserved domain cd04705 (similar to human GIII PLA(2) ). The sPLA(2) s of bacteria, fungi and marine invertebrates contain the conserved domain pfam09056 (prokaryotic PLA(2) ) that is the only conserved domain identified in fungal sPLA(2) s. Pfam06951 (GXII PLA(2) ) is present in bacteria and is widely distributed in eukaryotes. All conserved domains were present across mammalian sPLA(2) s, with the exception of cd04706 and pfam09056. Notably, no sPLA(2) s were found in Archaea. Phylogenetic analysis of sPLA(2) conserved domains reveals that two main clades, the cd- and the pfam-collection, exist, and that they have evolved via gene-duplication and gene-deletion events. These observations are consistent with the hypothesis that sPLA(2) s in eukaryotes shared common origins with two types of bacterial sPLA(2) s, and their persistence during evolution may be related to their role in phospholipid metabolism, which is fundamental for survival.
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PMID:Conserved domains and evolution of secreted phospholipases A(2). 2217 12

Vertebrate group XII phospholipases A(2) (GXII PLA(2), conserved domain pfam06951) are proteins with unique structural and functional features within the secreted PLA(2) family. In humans, two genes (GXIIA PLA(2) and GXIIB PLA(2)) have been characterised. GXIIA PLA(2) is enzymatically active whereas GXIIB PLA(2) is devoid of catalytic activity. Recently, putative homologues of the vertebrate GXII PLA(2)s were described in non-vertebrates. In the current study a total of 170 GXII PLA(2) sequences were identified in vertebrates, invertebrates, non-metazoan eukaryotes, fungi and bacteria. GXIIB PLA(2) was found only in vertebrates and the searches failed to identify putative GXII PLA(2) homologues in Archaea. Comparisons of the predicted functional domains of GXII PLA(2)s revealed considerable structural identity within the Ca(2+)-binding and the catalytic sites among the various organisms suggesting that functional conservation may have been retained across evolution. The preservation of GXII PLA(2) family members from bacteria to human indicates that they have emerged early in evolution and evolved via gene/genome duplication events prior to Eubacteria. Gene duplicates were identified in some invertebrate taxa suggesting that species-specific duplications occurred. The analysis of the GXII PLA(2) homologue genome environment revealed that gene synteny and gene order are preserved in vertebrates. Conservation of GXII PLA(2)s indicates that important functional roles involved in species survival and were maintained across evolution and may be dependent on or independent of the enzyme's phospholipolytic activity.
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PMID:Conservation of group XII phospholipase A2 from bacteria to human. 2290 2