Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.6.3.14 (ATP synthase)
 7,042 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Employing isoelectric focusing on immobilized pH gradients followed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) we have obtained a map of C. elegans proteins, from a mixed culture containing all developmental stages, presenting over 2000 spots within the window of isoelectric points (pI) 3.5-9 and a molecular mass of 10-200 kDa. Edman microsequencing yielded successful results in 12 out of 24 analyzed spots. All but one of the N-terminal sequences retrieved C. elegans sequences in cosmid and/or expressed sequence tag clones. Structurally related protein sequences found in data banks included enzymes in energy metabolism (cytochrome oxydase, ATP synthase, enolase), a fatty acid-binding protein, a translationally controlled tumor protein, an unknown C. elegans protein, an acidic ribosomal protein, a titin-like protein, a G-protein beta chain, cyclophilin, and cathepsin D. Experimental determination of N-termini allowed us to define sites of signal cleavage providing further information on the physiological role of the newly found C. elegans proteins. This report demonstrates the possibility of two-dimensional gel electrophoresis and Edman microsequencing in the elucidation of C. elegans proteome.
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PMID:Two-dimensional gel electrophoresis of Caenorhabditis elegans homogenates and identification of protein spots by microsequencing. 915 Sep 41

MURF-1, MURF-2 and MURF-3 are a specific class of RING finger proteins that are expressed in striated muscle tissues. MURF-1 has been suggested to act as an ubiquitin ligase, thereby controlling proteasome-dependent degradation of muscle proteins. Here, we performed yeast two-hybrid (YTH) screens of skeletal muscle cDNA libraries with MURF-1 baits to identify potential myocellular targets of MURF-1-dependent ubiquitination. This identified eight myofibrillar proteins as binding partners of MURF-1: titin, nebulin, the nebulin-related protein NRAP, troponin-I (TnI), troponin-T (TnT), myosin light chain 2 (MLC-2), myotilin and T-cap. YTH mating studies with MURF-1,2,3 baits indicated that these eight myofibrillar proteins are all targeted redundantly by both MURF-1 and MURF-2. Western blot studies on cardiac tissues from wild-type and MURF-1-deficient mice suggested that titin and nebulin were ubiquitinated at similar levels, and MLC-2 and TnI at reduced levels in MURF-1 KO mice. Mapping of the TnI and titin binding sites on MURF-1 peptide scans demonstrated their binding to motifs highly conserved between MURF-1 and MURF-2. Our data are consistent with a model in which MURF-1 and MURF-2 together target a specific set of myofibrillar proteins redundantly, most likely to control their ubiquitination-dependent degradation. Finally, our YTH screens identified the interaction of MURF-1 with 11 enzymes required for ATP/energy production in muscle including the mitochondrial ATP synthase and cytoplasmic creatine kinase. These data raise the possibility that MURF-1 may coordinately regulate the energy metabolism of mitochondrial and cytoplasmic compartments.
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PMID:MURF-1 and MURF-2 target a specific subset of myofibrillar proteins redundantly: towards understanding MURF-dependent muscle ubiquitination. 1596 62

Sarcopenia is the drastic loss of skeletal muscle mass and strength during ageing. In order to better understand the molecular pathogenesis of age-related muscle wasting, we have performed a DIGE analysis of young adult versus old rat skeletal muscle. Proteomic profiling revealed that out of 2493 separated 2-D spots, 69 proteins exhibited a drastically changed expression. Age-dependent alterations in protein abundance indicated dramatic changes in metabolism, contractile activity, myofibrillar remodelling and stress response. In contrast to decreased levels of pyruvate kinase (PK), enolase and phosphofructokinase, the mitochondrial ATP synthase, succinate dehydrogenase, malate dehydrogenase, isocitrate dehydrogenase and adenylate kinase (AK) were increased in senescent fibres. Higher expression levels of myoglobin and fatty acid binding-protein indicated a shift to more aerobic-oxidative metabolism in a slower-twitching aged fibre population. The drastic increase in alphaB-crystallin and myotilin demonstrated substantial filament remodelling during ageing. An immunoblotting survey of selected muscle proteins confirmed the pathobiochemical transition process in aged muscle metabolism. The proteomic analysis of aged muscle has identified a large cohort of new biomarkers of sarcopenia including opposite changes in PK and AK, which might be useful for the design of improved diagnostic procedures and/or therapeutic strategies to counteract ageing-induced muscle degeneration.
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PMID:Opposite pathobiochemical fate of pyruvate kinase and adenylate kinase in aged rat skeletal muscle as revealed by proteomic DIGE analysis. 1805 Feb 75