Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.3.3.1 (citrate synthase)
 4,488 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Understanding the functional genomics and proteomics of plasmodia underpins the development of new approaches to antimalarial chemotherapy. Although genome databanks (e.g. PlasmoDB) and biocomputing tools (e.g. PlasMit, PlasmoAP, PATS) are useful in providing a global albeit predictive view of the myriad of about 5000 genes, only 40% are annotated, with few cases of endorsed subcellular localizations of the corresponding proteins in animal models. Progress in plasmodial protein trafficking has been hampered by the lack of a simple yet reliable method for studying subcellular localization of plasmodial proteins. In this study, we have used a combination of fluorescent markers, organelle-specific probes, phase contrast microscopy, and confocal microscopy to locate a selection of signal peptides from 10 plasmodial proteins in CHO-K1 cells. These eukaryotic cells serve as an in vitro living system for studying the cellular destinations of four mitochondrial-targeted TCA cycle proteins (citrate synthase, CS; isocitrate dehydrogenase, ICDH; branched chain alpha-keto-acid dehydrogenase E1alpha subunit, BCKDH; succinate dehydrogenase flavoprotein-subunit, SDH), two nuclear-targeted proteins (histone deacetylase, HDAC; RNA polymerase, RPOL), two apicoplast-targeted proteins (pyruvate kinase 2, PK2; glutamate dehydrogenase, GDH), and two cytoplasmic resident proteins (malate dehydrogenase, MDH; glycerol kinase, GK). The respective localizations of these malarial proteins have complied with the selected molecular targets, viz. mitochondrial, nuclear and cytoplasmic. Interestingly, MDH that is widely known to be resident in eukaryotic mitochondria was found to be cytoplasmic, probably due to the absence of molecular target sequences. Since the localization of plasmodial proteins is central to the authentication of their pathophysiological roles, this experimental system will serve as a useful a priori approach.
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PMID:A relevant in vitro eukaryotic live-cell system for the evaluation of plasmodial protein localization. 1683 57

Poly(ADP-ribose) polymerases (PARPs) catalyze the transfer of multiple adenine diphosphate ribose (ADP-ribose) units from nicotinamide adenine dinucleotide (NAD) to substrate proteins. There are 17 PARPs in humans. Several PARPs, such as PARP-1 and Tankyrase-1, are known to play important roles in DNA repair, transcription, mitosis, and telomere length maintenance. To better understand the functions of PARPs at a molecular level, it is necessary to know what substrate proteins PARPs modify. Here we report clickable NAD analogues that can be used to label PARP substrate proteins. The clickable NAD analogues have a terminal alkyne group which allows the conjugation of fluorescent or affinity tags to the substrate proteins. Using this method, PARP-1 and tankyrase-1 substrate proteins were labeled by a fluorescent tag and visualized on SDS-PAGE gel. Using a biotin affinity tag, we were able to isolate and identify a total of 79 proteins as potential PARP-1 substrates. These include known PARP-1 substrate proteins, including histones and heterogeneous nuclear ribonucleoproteins. About 40% of the proteins were also identified in recent proteomic studies as potential PARP-1 substrates. Among the identified potential substrates, we further demonstrated that tubulin and three mitochondrial proteins, TRAP1 (TNF receptor-associated protein 1), citrate synthase, and GDH (glutamate dehydrogenase 1), are substrates of PARP-1 in vitro. These results demonstrate that the clickable NAD analogue is useful for labeling, in-gel detection, isolation, and identification of the substrate proteins of PARPs and will help to understand the biological functions of PARPs.
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PMID:Clickable NAD analogues for labeling substrate proteins of poly(ADP-ribose) polymerases. 2056 May 83

Activity-body size relationships for eight enzymes (citrate synthase, CS; lactate dehydrogenase, LDH; pyruvate kinase, PK; alanine aminotransferase, ala AT; aspartate aminotransferase, asp AT; glutamate dehydrogenase, GDH; glucose-6-phosphate dehydrogenase, G6Pdh; and nucleoside diphosphate kinase, NDPK) were examined in the brine shrimp, Artemia franciscana. The animals were fed on the alga Dunaliella salina, which was provided in three concentrations representing a 25-fold range. Enzyme activities per animal (Y) were regressed against body size (M, expressed as dry mass or protein) in the form of the allometric equation, log Y = log a + b log M, where a and b are fitted constants. For all enzymes considered, the value of the scaling exponent (b) was significantly higher when dry mass was used, as a body size index, than when protein mass was used. Therefore, the index of body size chosen can influence the exponent obtained in allometric studies. Although specific growth rates of different cultures varied greatly, no significant differences in scaling relationships were found between cultures for any enzyme. For many enzymes, growth rate may not be a source of variation in scaling relationships. Unlike the other enzymes examined, the log-transformed NDPK activity versus log-transformed mass was not linear; NDPK activity reached a plateau. Variation in NDPK scaling relationships with growth may provide a means to predict growth rate in Artemia.
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PMID:Relationship Between Body Size, Growth Rate, and Maximal Enzyme Activities in the Brine Shrimp, Artemia franciscana. 2931 70