Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.6.1.3 (ATPase)
 65,361 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The yeast YAP3 gene encodes an aspartyl endoprotease that cleaves precursor proteins at selected pairs of basic amino acids and after single arginine residues. Biosynthetic studies of this proprotein processing enzyme indicate that Yap3 is predominantly cell-associated and migrates as a approximately 160-kDa protein on SDS-polyacrylamide gel electrophoresis. Nearly equal amounts of Yap3 are immunodetected in a-haploid, alpha-haploid, and a/alpha-diploid yeast, demonstrating that the expression of YAP3 is not mating type-specific. As shown by endoglycosidase H treatment, which drastically reduces both the estimated molecular mass and the heterogeneity of the protein on SDS-polyacrylamide gel electrophoresis (68 versus 160 kDa), the oligosaccharides N-linked to the protein are subjected to extensive outer chain mannosylation. Outer chain sugar mannosylation takes place in the Golgi apparatus and is commonly found on yeast secreted glycoproteins and/or cell wall mannoproteins. Treatment of the total yeast membranes with chemical agents known to disrupt protein-protein and protein-lipid interactions reveal that Yap3 is membrane-associated. Based upon the release of the membrane-bound form by bacterial phosphatidylinositol phospholipase C digestion and metabolic labeling of the protein with myo-[3H]inositol, Yap3 owes its association with the membrane to the addition of a glycophosphatidylinositol anchor. The cellular localization of Yap3 has been addressed by subcellular fractionation studies. In both differential centrifugation of intracellular organelles and sucrose density gradients, the bulk of Yap3 at steady state co-localizes with the plasma membrane azide-insensitive ATPase. Furthermore, consistent with the transport of Yap3 to the plasma membrane, the endoprotease sediments with secretory vesicles which accumulate at restrictive temperature in the late secretory mutant sec1-1. We therefore conclude that the endoprotease encoded by YAP3 is a glycophosphatidylinositol-anchored protein, which can process substrates both intracellularly and at the cell surface.
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PMID:The yeast proprotein convertase encoded by YAP3 is a glycophosphatidylinositol-anchored protein that localizes to the plasma membrane. 765 70

The alkyl-lysophospholipids are a new family of anticancer drugs which target the cell membrane as their site of action. Enzymes involved in signal transduction (protein kinase C and phosphatidylinositol phospholipase C), phospholipid biosynthesis (lysophosphatidyl acyltransferase and CTP:cholinephosphate cytidylyltransferase) and maintenance of membrane integrity (Na,K ATPase sodium pump) are inhibited. A unique feature of the alkyl-lysophospholipids is their selective cytotoxicity to neoplastic cells. This suggests that the compound would be an excellent agent for purging residual leukemic cells from marrows of patients in remission prior to autologous bone marrow transplantation. Preclinical studies in a murine leukemia model and in an in vitro human system demonstrated successful elimination of leukemic cells from a mixture of normal and leukemic marrows. Twenty-nine poor risk patients with acute leukemia underwent autologous bone marrow transplantation and were reinfused with marrow treated in vitro with edelfosine. Nine of these patients remain in remission free of leukemia from 368 to 1369 days. These encouraging results warrant further investigation.
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PMID:Bone marrow purging in acute leukemia with alkyl-lysophospholipids: a new family of anticancer drugs. 802 24