Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P20226 (TATA-binding protein)
 1,297 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The SUD1 gene was identified during a hunt for mutants that are able to express an sta1 gene (encoding an extracellular glucoamylase) lacking an upstream activation sequence (UAS) for transcription. A null allele of sud1 alleviated the transcriptional defect of the UAS-less sta1 and also suppressed mutations in trans-acting genes (GAM1/SNF2 and GAM3/ADR6) required for transcription of STA1. The mutation also increased expression from various core promoters (CYC1, CUP1, HIS3, PUT1, and PUT2), suggesting that the SUD1 protein is a global transcriptional regulator that plays a negative role at or near the TATA element. However, the SUD1 function was ineffective on promoters containing a UAS from either STA1 or GAL10 under derepressed conditions. The sud1 mutation suppressed the salt-sensitive cell growth phenotype caused by elevated levels of the TATA-binding protein (SPT15), further suggesting a transcriptional role for SUD1. sud1 cells showed additional pleiotropic phenotypes: temperature-sensitive (ts) growth, reduced efficiencies of sporulation, and sensitivity to heat shock and nitrogen starvation. The SUD1 gene is predicted to encode a 64 kDa, hydrophilic protein.
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PMID:Isolation and characterization of the SUD1 gene, which encodes a global repressor of core promoter activity in Saccharomyces cerevisiae. 826 36

Transcription initiation in Archaea (archaebacteria) resembles the eucaryotic process, having been shown to involve TATA box-like promoter regions as well as TATA-binding protein and TFIIB homologs. However, little is known about transcription regulation in archaea. We have previously demonstrated that transcripts of nifHDK2 genes, encoding Methanosarcina barkeri nitrogenase, are present in N2-grown cells but not in ammonium-grown cells, indicating that nif transcription is regulated by the nitrogen source. In this study, we detected proteins in M. barkeri cell extracts that bind specifically to DNA containing the putative promoter region of nifHDK2. No binding was found when the promoter region was deleted from the DNA. A competition assay showed that the methyl coenzyme M reductase (mcr) promoter region DNA and the nifH2 promoter region DNA competed for a common factor(s). There was no binding to the nifH2 promoter region by extracts of ammonium-grown cells, but there was binding by these extracts to promoter regions for mcr genes, which are presumably constitutively expressed. Interestingly, extracts of ammonium-grown cells inhibited binding to the nif promoter region by extracts of N2-grown cells. Fractionation of extracts of ammonium-grown cells with a heparin-Sepharose column resolved them into a fraction eluting at 0 M NaCl, which inhibited binding by extracts of N2-grown cells, and a fraction eluting at 0.5 to 0.75 M NaCl, which showed binding to the promoter region. These results are congruent with a model for regulation of nif gene expression in M. barkeri in which a substance present in ammonium-grown cells inhibits DNA binding by a transcription-associated protein or proteins.
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PMID:Interactions between the promoter regions of nitrogenase structural genes (nifHDK2) and DNA-binding proteins from N2- and ammonium-grown cells of the archaeon Methanosarcina barkeri 227. 957 59

PT-ACRAMTU ([PtCl(en)(ACRAMTU-S)](NO(3))(2), en = ethane-1,2-diamine, ACRAMTU = 1-[2-(acridin-9-ylamino)ethyl]-1,3-dimethylthiourea) is a cytotoxic platinum-acridine conjugate previously shown to form adducts with the N3 endocyclic nitrogen of adenine in the DNA minor groove. This unusual observation and our prior determination of the pronounced 5'-TA/TA base-step affinity of the drug have prompted us to investigate effects of these adducts on DNA minor groove binding proteins. Here, we used electrophoretic mobility shift assays to study the recognition of a PT-ACRAMTU-modified TATA box sequence by TATA-binding protein (TBP). The frequency of PT-ACRAMTU adducts in the minor groove of the TATA box was varied by selective elimination of potential major groove and minor groove binding sites in a 24-bp probe sequence through incorporation of deaza nucleobases. The most dramatic effect on TBP binding was observed in a duplex substituted with 7-deaza-G and 7-deaza-A, which reduced binding by as much as 73% compared to an unplatinated duplex. In contrast, elimination of A-N3 binding sites had no significant effect on TBP binding, suggesting that minor groove adducts of PT-ACRAMTU are the cause of inhibition. This notion was further corroborated by efficient platinum-mediated photo-cross-linking of the drug-modified DNA to TBP. PT-ACRAMTU appears to be the first platinum-based drug capable of targeting DNA sequences critical for transcription initiation. The biological consequences of PT-ACRAMTU's minor groove adducts are discussed.
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PMID:DNA minor groove adducts formed by a platinum-acridine conjugate inhibit association of tata-binding protein with its cognate sequence. 1610 10

The E1-like superfamily is central to ubiquitin (Ub) conjugation, biosynthesis of cysteine, thiamine, and MoCo, and several secondary metabolites. Yet, its functional diversity and evolutionary history is not well understood. We develop a natural classification of this superfamily and use it to decipher the major adaptive trends occurring in the evolution of the E1-like superfamily. Within the Rossmann fold, E1-like proteins are closest to NAD(P)/FAD-dependent dehydrogenases and S-AdoMet-dependent methyltransferases. Hence, their phosphotransfer activity is an independent catalytic "invention" with respect to such activities seen in other Rossmannoid folds. Sequence and structure analysis reveals a striking diversity of residues and structures involved in adenylation, sulfotransfer, and substrate binding between different E1-like families, allowing us to predict previously uncharacterized functional adaptations. E1-like proteins are fused to several previously undetected domains, such as a predicted sulfur transfer domain containing a novel superfamily of the TATA-binding protein fold, different types of catalytic domains, a novel winged helix-turn-helix domain and potential adaptor domains related to Ub conjugation. On the basis of these fusions, we develop a generalized model for the linking of E1 catalyzed adenylation/thiolation with further downstream reactions. This is likely to involve a dynamic interplay between the E1 active sites and diverse fused C-terminal domains. We also predict participation of E1-like domains in previously uncharacterized bacterial secondary metabolism pathways, new cysteine biosynthesis systems, such as those associated with archaeal O-phosphoseryl tRNA, metal-sulfur cluster assembly (e.g., in nitrogen fixation) and Ub-conjugation. Evolutionary reconstructions suggest that the last universal common ancestor contained a single E1-like domain possessing both phosphotransfer and thiolating activities and participating in multiple sulfotransfer reactions. The E1-like superfamily subsequently expanded to include 26 families clustering into three major radiations. These are broadly involved in Ub activation, cofactor and cysteine biosynthesis, and biosynthesis of secondary metabolites. In light of this, we present evidence that in eukaryotes other E1-like enzymes such as Urm1 were independently recruited for Ubl conjugation, probably functioning without conventional E2-like enzymes.
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PMID:Natural history of the E1-like superfamily: implication for adenylation, sulfur transfer, and ubiquitin conjugation. 1908 47

The SPT15 gene encodes a Saccharomyces cerevisiae TATA-binding protein, which is able to globally control the transcription levels of various metabolic and regulatory genes. In this study, a SPT15 gene mutant (S42N, S78R, S163P, and I212N) was expressed in S. cerevisiae BY4741 (BSPT15-M3), of which effects on fermentative yeast properties were evaluated in a series of culture types. By applying different nitrogen sources and air supply conditions in batch culture, organic nitrogen sources and microaerobic condition were decided to be more favorable for both cell growth and ethanol production of the BSPT15-M3 strain than the control S. cerevisiae BY4741 strain expressing the SPT15 gene (BSPT15wt). Microaerobic fed-batch cultures of BSPT15-M3 with glucose shock in the presence of high ethanol content resulted in a 9.5-13.4% higher glucose consumption rate and ethanol productivity than those for the BSPT15wt strain. In addition, BSPT15-M3 showed 4.5 and 3.9% increases in ethanol productivity from cassava hydrolysates and corn starch in simultaneous saccharification and fermentation processes, respectively. It was concluded that overexpression of the mutated SPT15 gene would be a potent strategy to develop robust S. cerevisiae strains with enhanced cell growth and ethanol production abilities.
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PMID:Expression of a mutated SPT15 gene in Saccharomyces cerevisiae enhances both cell growth and ethanol production in microaerobic batch, fed-batch, and simultaneous saccharification and fermentations. 2816 13