Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.30.1 (S1 nuclease)
3,660 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Giardia lamblia is believed to be the earliest branching derivative from the eucaryotic lineage. Genomic and cDNA clones encoding the giardia NADP-dependent glutamate dehydrogenase have been isolated and characterized. Southern hydridization using genomic DNA indicates that the gene encoding this activity is unique and single copy. Primer extension, S1 nuclease protection, and genomic and cDNA sequence analysis demonstrate that gene transcripts are initiated within a conserved AT-rich sequence element immediately preceding the ATG translation initiation codon and the short 5' untranslated region is not extended by transsplicing. The open reading frame is 1350 nucleotides in length and encodes a protein of 449 amino acids. The reading frame is not interrupted by introns and the primary transcript is probably not subjected to RNA editing. In the strictly anaerobic metabolism of giardia, NADP-dependent glutamate dehydrogenase activity participates along with alanine aminotransferase, in the cyclic dissipation of reducing equivalents (NADPH) through the conversion of pyruvate to alanine. The deduced amino acid sequence of the giardia protein exhibits substantial homology to numerous fungal and eubacterial NADP-dependent glutamate dehydrogenases. Comparisons of alignment gap positions and amino acid identities indicate that the giardia sequence is at least as similar or more similar to the eubacterial sequence than it is to the fungal sequence. This supports the hypothesis that giardia diverged very early from the eucaryotic lineage.
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PMID:Isolation and characterization of a NADP-dependent glutamate dehydrogenase gene from the primitive eucaryote Giardia lamblia. 155 91

Several species of fish from the genus Poeciliopsis differ dramatically in their response to the carcinogen N-nitrosodiethylamine (NDEA). The differential induction of tumors among genotypes exposed to NDEA may, in part, result from differences in liver cytochrome P450pj activity (the piscine equivalent of mammalian P450j). Evidence for the existence of cytochrome P450pj activity and mRNA expression has been found in several Poeciliopsis genotypes (species and strains). Biochemical evidence suggests that a microsomal cytochrome P450 enzyme catalyzes the metabolism of NDEA to acetaldehyde and other intermediates in Poeciliopsis. This reaction was inhibited by carbon monoxide, and required molecular oxygen and reducing equivalents (NADPH). Differences were found in maximal activity as well as temperature optima among genotypes. Poeciliopsis, a livebearing fish from desert streams of northwestern Mexico, appears to have thermal optima for cytochrome P450pj activity between 25 and 30 degrees C depending on the genotype. Western blot analysis (using anti-rat P450IIE1 antibodies) detected a 55-60 kd band in microsomes isolated from rat and Poeciliopsis. Using a 49mer probe specific for rat cytochrome P450j, Northern blots revealed a 3.3 kb mRNA from livers of a Poeciliopsis genotype and rat, but none in muscle mRNA from either organism. S1 nuclease protection assays, using the same probe, revealed that a mRNA fragment protected by the probe against digestion was induced on exposure of the whole organism to ethanol (via uptake from the aquatic environment). The assays also demonstrated that ethanol treatments both induced and suppressed this mRNA, depending on concentration and exposure time.
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PMID:Nitrosodiethylamine metabolism in the viviparous fish Poeciliopsis: evidence for the existence of liver P450pj activity and expression. 201 28

The untranslated first exon and the 5'-flanking region for the rat liver NADPH-cytochrome P450 oxidoreductase gene has been isolated from a Wistar-Furth genomic library. The remainder of the gene is composed of 15 exons which code for the mature protein and a 3'-nontranslated segment (T. D. Porter et al. Biochemistry, 1990, 29, 9814-9818). The 56-bp first exon resides 30.5 kb upstream from exon two, making the total gene length approximately 50 kb. While the region surrounding the start site (TCAGAGAC) was found to be homologous to a eukaryotic cap signal, the 5' flanking region possesses neither a TATA nor a CCAAT box. Instead it contains five GC-rich hexanucleotide consensus sequences for the transcription factor Sp1. These features clearly distinguish it from genes encoding other members of the mixed-function oxidase system, the cytochromes P450. Primer extension analysis and S1 nuclease mapping identified multiple transcriptional start sites. In many respects, the TATA-less oxidoreductase promoter resembles the promoter regions of dihydrofolate reductase and other housekeeping genes. Northern blot analysis demonstrates that this promoter is modulated by phenobarbital and trans-stilbene oxide, known inducers of oxidoreductase.
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PMID:NADPH cytochrome P-450 oxidoreductase gene: identification and characterization of the promoter region. 817 32