Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.1.1.5 (neuropathy target esterase)
1,070 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Mammalian tissues contain small form and large form lysophospholipases. Here we report the cloning, sequence, and expression of cDNA encoding the latter form of lysophospholipase using antibody raised against the enzyme purified from rat liver supernatant (Sugimoto, H., and Yamashita, S. (1994) J. Biol. Chem. 269, 6252-6258). The 2,539-base pair cDNA encoded 564 amino acid residues with a calculated Mr of 60,794. The amino-terminal two-thirds of the deduced amino acid sequence significantly resembled Escherichia coli asparaginase I with the putative asparaginase catalytic triad Thr-Asp-Lys and was followed by leucine zipper motif. The carboxyl-terminal region carried ankyrin repeat. When the cDNA was transfected into HEK293 cells, not only lysophospholipase activity but also asparaginase and platelet-activating factor acetylhydrolase activities were expressed. Reverse transcription-polymerase chain reaction revealed that the transcript occurred at high levels in liver and kidney but was hardly detectable in lung and heart from which large form lysophospholipases had been purified, suggesting the presence of multiple forms of large form lysophospholipase in mammalian tissues.
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PMID:Cloning and expression of cDNA encoding rat liver 60-kDa lysophospholipase containing an asparaginase-like region and ankyrin repeat. 957 12

The Group VI 80-kDa Ca2+-independent phospholipase A2 (iPLA2) has been purified from murine P388D1 macrophages and Chinese hamster ovary (CHO) cells. The amino acid sequence of the iPLA2 has been determined and shown to contain a lipase consensus sequence and eight ankyrin repeats, which makes it distinct from Group I-V PLA2s. This enzyme appears to play a key role in mediating basal phospholipid remodeling. We now report that the Group VI iPLA2 displays interfacial activation toward short chain phospholipids, 1-octanoyl-2-heptanoyl-sn-glycero-3-phosphocholine, 1,2-diheptanoyl-sn-glycero-3-phosphocholine, and 1,2-dihexanoyl-sn-glycero-3-phosphocholine micelles. ATP protects the iPLA2 from a loss in activity as a result of prolonged incubation during the assay. Hence higher enzyme activity is observed in the presence than in the absence of ATP. Similar protection was obtained with glycerol. In addition, the iPLA2 exhibits multiple activities which are strongly dependent on substrate presentation. The lysophospholipase activity of this enzyme was diminished by Triton X-100 and stimulated by glycerol. With the combination of 50 microM Triton X-100 and 50% glycerol, the enzyme's lysophospholipase activity achieved equivalent activity to its PLA2 activity. The iPLA2 displayed both lysophospholipid/transacylase and phospholipid/transacylase activity, supporting the conclusion that the mechanism of action of iPLA2 proceeds through an acyl-enzyme intermediate as proposed for the Group IV cPLA2.
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PMID:Interfacial activation, lysophospholipase and transacylase activity of group VI Ca2+-independent phospholipase A2. 963 Jul 2

The classical Ca(2+)-independent phospholipase A(2) enzyme, now known as Group VIA PLA(2), was initially purified and characterized from the P388D(1) macrophage-like cell line. The corresponding cDNA was subsequently cloned from a variety of sources, and it is now known that multiple splice variants of the enzyme are expressed, some of which may act as negative regulators of the active enzyme. Group VIA PLA(2) has a consensus lipase motif (GTSTG) containing the catalytic serine, is 85-88 kDa, and exists in an aggregated form. The enzyme contains multiple ankyrin repeats, which may play a role in oligomerization. The Group VIA enzyme exhibits lysophospholipase activity as well as phospholipase A(2) activity, and it is capable of hydrolyzing a wide variety of phospholipid substrates. A major function of Group VIA PLA(2) is to mediate phospholipid remodeling, but the enzyme may play other roles as well. Other Ca(2+)-independent PLA(2) enzymes have more recently been identified, and it may be possible to discriminate between the various Ca(2+)-independent PLA(2) enzymes based on sequence or inhibitor-sensitivity. However, the physiological functions of the newly identified enzymes have yet to be elucidated.
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PMID:Calcium-independent phospholipase A(2): structure and function. 1108 Jun 74

The group VIA PLA2 is a member of the PLA2 superfamily. This enzyme, which is cytosolic and Ca2+-independent, has been designated iPLA2beta to distinguish it from another recently cloned Ca2+-independent PLA2. Features of iPLA2beta molecular structure offer some insight into possible cellular functions of the enzyme. At least two catalytically active iPLA2beta isoforms and additionalsplicing variants are derived from a single gene that consists of at least 17 exons located on human chromosome 22q13.1. Potential tumor suppressor genes also reside at or near this locus. Structural analyses reveal that iPLA2beta contains unique structural features that include a serine lipase consensus motif (GXSXG), a putative ATP-binding domain, an ankyrin-repeat domain, a caspase-3 cleavage motif DVTD138Y/N, a bipartite nuclear localization signal sequence, and a proline-rich region in the human long isoform. iPLA2beta is widely expressed among mammalian tissues, with highest expression in testis and brain. iPLA2beta prefers to hydrolyze fatty acid at the sn-2 fatty acid substituent but also exhibits phospholipase A1, lysophospholipase, PAF acetylhydrolase, and transacylase activities. iPLA2beta may participate in signaling, apoptosis, membrane phospholipid remodeling, membrane homeostasis, arachidonate release, and exocytotic membrane fusion. Structural features and the existence of multiple splicing variants of iPLA2beta suggest that iPLA2beta may be subject to complex regulatory mechanisms that differ among cell types. Further study of its regulation and interaction with other proteins may yield insight into how its structural features are related to its function.
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PMID:The molecular biology of the group VIA Ca2+-independent phospholipase A2. 1152 80

In our recent paper in the Plant Journal, we reported that Arabidopsis thaliana lysophospholipase 2 (lysoPL2) binds acyl-CoA-binding protein 2 (ACBP2) to mediate cadmium [Cd(II)] tolerance in transgenic Arabidopsis. ACBP2 contains ankyrin repeats that have been previously shown to mediate protein-protein interactions with an ethylene-responsive element binding protein (AtEBP) and a farnesylated protein 6 (AtFP6). Transgenic Arabidopsis ACBP2-overexpressors, lysoPL2-overexpressors and AtFP6-overexpressors all display enhanced Cd(II) tolerance, in comparison to wild type, suggesting that ACBP2 and its protein partners work together to mediate Cd(II) tolerance. Given that recombinant ACBP2 and AtFP6 can independently bind Cd(II) in vitro, they may be able to participate in Cd(II) translocation. The binding of recombinant ACBP2 to [(14)C]linoleoyl-CoA and [(14)C]linolenoyl-CoA implies its role in phospholipid repair. In conclusion, ACBP2 can mediate tolerance to Cd(II)-induced oxidative stress by interacting with two protein partners, AtFP6 and lysoPL2. Observations that ACBP2 also binds lysophosphatidylcholine (lysoPC) in vitro and that recombinant lysoPL2 degrades lysoPC, further confirm an interactive role for ACBP2 and lysoPL2 in overcoming Cd(II)-induced stress.
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PMID:Protein interactors of acyl-CoA-binding protein ACBP2 mediate cadmium tolerance in Arabidopsis. 2065 76

Lysophospholipids (LPLs) are important lipid-signaling molecules in plants, of which lysophosphatidylcholine (lysoPC) is one of the most well-characterized LPLs, having important roles in plant stress responses. It is broken down by lysophospholipases, but the molecular mechanism involved in lysoPC degradation is unclear. Recombinant Arabidopsis thaliana ACYL-CoA-BINDING PROTEIN2 (AtACBP2) has been reported to bind lysoPC via its acyl-CoA-binding domain and also LYSOPHOSPHOLIPASE 2 (AtLYSOPL2) via its ankyrin repeats in vitro To investigate the interactions of AtACBP2 with AtLYSOPL2 and lysoPC in more detail, we conducted isothermal titration calorimetry with AtACBP2_70-354, an AtACBP2 derivative consisting of amino acids 70-354, containing both the acyl-CoA-binding domain and ankyrin repeats. We observed that the interactions of AtACBP2_70-354 with AtLYSOPL2 and lysoPC were both endothermic, favored by solvation entropy and opposed by enthalpy, with dissociation constants in the micromolar range. Of note, three AtLYSOPL2 catalytic triad mutant proteins (S147A, D268A, and H298A) bound lysoPC only weakly, with an exothermic burst and dissociation constants in the millimolar range. Furthermore, the binding affinity of lysoPC-premixed AtACBP2_70-354 to AtLYSOPL2 was 10-fold higher than that of AtACBP2_70-354 alone to AtLYSOPL2. We conclude that AtACBP2 may play a role in facilitating a direct interaction between AtLYSOPL2 and lysoPC. Our results suggest that AtACBP2_70-354 probably binds to lysoPC through a hydrophobic interface that enhances a hydrotropic interaction of AtACBP2_70-354 with AtLYSOPL2 and thereby facilitates AtLYSOPL2's lysophospholipase function.
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PMID:Thermodynamic insights into an interaction between ACYL-CoA-BINDING PROTEIN2 and LYSOPHOSPHOLIPASE2 in Arabidopsis. 3078 48

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