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

Phospholamban, through modulation of sarcoplasmic reticulum calcium-ATPase activity, is a key regulator of cardiac diastolic function. Alterations in phospholamban expression may define parameters of muscle relaxation. In experimental animals, phospholamban is differentially expressed in various striated and smooth muscles, and within the four chambers of the heart. Decreased phospholamban expression within the heart during heart failure has also been observed. Furthermore, regulatory elements of mammalian phospholamban genes remain poorly defined. To extend these studies to humans, we (1) characterized phospholamban expression in various human organs, (2) isolated genomic clones encoding the human phospholamban gene, and (3) prepared human phospholamban promoter/luciferase reporter constructs and performed transient transfection assays to begin identification of regulatory elements. We observed that human ventricle and quadriceps displayed high levels of phospholamban transcripts and proteins, with markedly lower expression observed in smooth muscles, while the right atria also expressed low levels of phospholamban. The human phospholamban gene structure closely resembles that reported for chicken, rabbit, rat, and mouse. Comparison of the human to other mammalian phospholamban genes indicates a marked conservation of sequence for at least 217 bp upstream of the transcription start site, which contains conserved motifs for GATA, CP1/NFY, M-CAT-like, and E-box elements. Transient transfection assays with a series of plasmids containing deleted 5' flanking regions (between -2530 and -66 through +85) showed that sequences between -169 and the CP1-box at -93 were required for maximal promoter activity in neonatal rat cardiomyocytes. Activity of these reporters in HeLa cells was markedly lower than that observed in rat cardiomyocytes, suggesting at least a partial tissue selectivity of these reporter constructs.
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PMID:The human phospholamban gene: structure and expression. 1019 97

Dark-grown Euglena gracilis strain Z were exposed to white light which induces chloroplast development including a massive formation of thylakoid membranes. Thylakoid membranes were isolated from greening cells at various times from 12 to 72 h following light-exposure. The temporal appearance in the membranes of the three main chlorophyll-protein complexes (CP1, CPa, LHCP) and the N,N(1)?dicyclohexylcarbodiimide (DCCD)-binding CF(0)-IH subunit of the coupling-factor ATPase was assessed. When the cells were greened on a medium containing the readily-metabolized carbon source, ethanol, LHCP was detected as early as 12 h, and both CP1 and CPa were detected in low quantity up to 36 h and then increased. CP1, CPa and LHCP were detected as green complexes on polyacrylamide gels earalier during greening when cells were greened on resting medium compared to cells greened in the presence of ethanol. Photosystem I activity was detected at 12 h, photosystem II activity at 18 to 24 h, and water-splitting and whole electron transport chain activities after 24 h. Correlations are made between the temporal appearances of these activities and of the chlorophyll-protein complexes. The DCCD- binding CF(0)-IH was detected in the membrane at 12 h and increased in amount thereafter.
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PMID:Temporal Appearance of Chlorophyll-Protein Complexes and the N,N -Dicyclohexylcarbodiimide-Binding Coupling Factor(0)?Subunit III in Forming Thylakoid Membranes of Euglena gracilis. 2319 27

The antibiotic resistance (ARE) subfamily of ABC (ATP-binding cassette) proteins confers resistance to a variety of clinically important ribosome-targeting antibiotics and plays an important role in infections caused by pathogenic bacteria. However, inhibitors of ARE proteins have rarely been reported. Here, OptrA, a new member of the ARE proteins, was used to study inhibitors of these types of proteins. We first confirmed that destroying the catalytic activity of OptrA could restore the sensitivity of host cells to antibiotics. Then, fragment-based screening, a drug screening method, was used to screen for inhibitors of OptrA. The competitive saturation transfer difference experiments, docking, and molecular dynamics were used to determine the binding sites and mode of interactions between OptrA and fragment screening hits. In this study, we first find a novel and specific inhibitor of OptrA (CP1), which suppressed the ATPase activity of OptrA in vitro by 30%. A hydrogen bond formed between the 8-position phenylcyclic cyano group in CP1 and the amino acid residue Lys-271 allows CP1 to form a stable complex with OptrA protein. These findings provide a theoretical basis for the further optimization of the inhibitor structure to obtain inhibitors with higher efficiencies.
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PMID:A novel inhibitor of the new antibiotic resistance protein OptrA. 2967 47