Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Binding of simple homopolymeric sequences to Drosophila melanogaster nuclear proteins has been studied. Proteins with Mr 65-72 kDa have been found, which specifically bind to synthetic poly[d(T-G)].poly[d(C-A)], as well as to D. melanogaster DNA containing a block of poly[d(T-G)].poly[d(C-A) 40 b.p. in length. It has been shown, that these proteins bind only to poly[d(T-G).poly[d(C-A)] and not to other types of simple sequences, for example poly[d(G-A)].poly[d(T-C)] and poly[d(A-T)].
Mol Biol (Mosk)
PMID:[Nuclear proteins from Drosophila melanogaster specifically binding to simple homopolymeric sequences of poly[d(T-G)].poly[d(C-A)] type]. 284 17

The homeo box gene even-skipped (eve) encodes a 376-amino-acid protein that binds with high affinity to sequences located near the 5' termini of the eve and en genes. The 5' en sites are A + T rich and contain copies of the 10-base-pair (bp) consensus sequence T-C-A-A-T-T-A-A-A-T. In contrast, the 5' eve sites are G + C rich and contain the 9-bp sequence T-C-A-G-C-A-C-C-G. Among the five different homeo box proteins that have been tested for binding, eve is unique in that it shows virtually equal preference for the A + T-rich 5' en binding sites and the G + C-rich 5' eve sites. Most of the other proteins bind with a relatively higher affinity to the en sites than to the eve sites. In an effort to identify the regions of the eve protein that are responsible for its efficient binding to both classes of recognition sequences, we analyzed the DNA-binding properties of various mutant eve proteins. These studies suggest that the homeo domain of the eve protein is responsible for both binding activities. However, mutations in distant regions of the protein influenced the binding behavior of the eve homeo domain and caused a reduction in binding to the G + C class of recognition sites. We propose that the protein context of the homeo domain can influence its DNA-binding properties.
Mol Cell Biol 1988 Nov
PMID:DNA-binding activities of the Drosophila melanogaster even-skipped protein are mediated by its homeo domain and influenced by protein context. 290 20

We have identified and characterized the structure of the Spec1 gene in the sea urchin Strongylocentrotus purpuratus. In earlier studies we demonstrated that a small family of messenger RNAs, termed Spec mRNAs for S. purpuratus ectodermal mRNAs, begins to accumulate 20 hours after fertilization in ectoderm cells of the sea urchin embryo. The Spec mRNAs code for a group of low molecular weight proteins belonging to the troponin C superfamily. Spec1 transcripts, the predominant mRNAs of the family, are heterogeneous in their 3' untranslated sequences but code for a single protein, recently shown to be a calcium-binding protein. Spec complementary DNA clones were used to isolate genomic clones from two lambda libraries. These genomic clones comprise a 41 kb (kb = 10(3) bases or base-pairs) region of the S. purpuratus genome and contain a Spec1 gene closely linked to another Spec gene, Spec2c. The Spec1 gene is 10.3 kb in length and contains six exons. The genomic clones containing the Spec1 gene can be placed into two groups based on restriction fragment length differences and differences in hybridization strengths using probes derived from Spec1 3' untranslated regions. Evidence that these groups probably correspond to two alleles of the Spec1 gene was obtained by probing genomic DNA blots of sperm DNA from different individuals with 3' untranslated sequences of Spec1 complementary DNA clones. These blots show that two of the Spec1 mRNAs we have characterized, and probably a third, are alleles of the Spec1 gene. Thus, there appears to be a single polymorphic Spec1 gene in the sea urchin genome. We used S1 protection and primer extension procedures to map the 5' end of the Spec1 gene. Results from these experiments indicate that the initiation of transcription of the Spec1 mRNA begins at an A residue 220 bases from the 3' end of the first exon. Adding support to this claim, cannonical T-A-T-A and C-A-A-T sequences, indicative of many eukaryotic promoters, are found 23 bases and 60 bases upstream from this site, respectively. Analysis of sequences within a few kb of the Spec1 gene show that there are five members of a repetitive sequence family near the gene, three upstream and two downstream. The 5' leader sequence of another Spec mRNA, Spec2a, also contains a member of this repeat family.(ABSTRACT TRUNCATED AT 400 WORDS)
J Mol Biol 1985 Nov 20
PMID:Structure of the Spec1 gene encoding a major calcium-binding protein in the embryonic ectoderm of the sea urchin, Strongylocentrotus purpuratus. 293 38

The antitumor antibiotic netropsin has been co-crystallized with a double-helical B-DNA dodecanucleotide of sequence: C-G-C-G-A-A-T-T-BrC-G-C-G, and the structure of the complex has been solved by X-ray diffraction at a resolution of 2.2 A. The structure has been refined independently by Jack-Levitt and Hendrickson-Konnert least-squares methods, leading to a final residual error of 0.257 by the Jack-Levitt approach (0.211 for two-sigma data) or 0.248 by the Hendrickson-Konnert approach, with no significant difference between refined structures. The netropsin molecule displaces the spine of hydration and fits snugly within the minor groove in the A-A-T-T center. It widens the groove slightly and bends the helix axis back by 8 degrees, but neither unwinds nor elongates the double helix. The drug molecule is held in place by amide NH hydrogen bonds that bridge adenine N-3 and thymine O-2 atoms, exactly as with the spine of hydration. The requirement of A X T base-pairs in the binding site arises because the N-2 amino group of guanine would demand impermissibly close contacts with netropsin. It is proposed that substitution of imidazole for pyrrole in netropsin should create a family of "lexitropsins" capable of reading G X C-containing base sequences.
J Mol Biol 1985 Jun 25
PMID:Binding of an antitumor drug to DNA, Netropsin and C-G-C-G-A-A-T-T-BrC-G-C-G. 299 36

On the basis of the observation that dnaA protein binds preferentially to DNA fragments carrying the Escherichia coli chromosomal replication origin (oriC), the binding sites were investigated by DNase I footprinting. As a result, three strong binding sites were identified in the minimal oriC sequence. The respective binding sites were 16 to 17 base-pairs long, and contained a common sequence (5') T-G-T-G-(G/T)-A-T-A-A-C (3') in the middle, although their polarities were not the same. Since mutants defective in function for autonomous replication have been isolated in the corresponding positions of the common sequence at each binding site, dnaA protein-binding at these sites seems to be significant for replication initiation.
J Mol Biol 1985 Aug 05
PMID:Sites of dnaA protein-binding in the replication origin of the Escherichia coli K-12 chromosome. 299 81

The expression of the Saccharomyces cerevisiae CYC1 gene, which encodes iso-1-cytochrome c, produces a family of messenger RNAs whose 5' ends map in the region from position +7 to -93 relative to the first nucleotide at position +1 of the protein-coding DNA sequence. The mechanism of transcription initiation of the CYC1 gene has been examined by using linker-scanning deletions and gene fusions. The various CYC1 derivatives with mutations in the 5' non-coding region were constructed, reintroduced into yeast using a multicopy plasmid, and the mRNA starts mapped by primer extension. The results indicate that four, and possibly five T-A-T-A sequences are located within the 5' non-coding region of the CYC1 gene, and that each T-A-T-A is required for a specific subset of mRNA starts. This conclusion has been confirmed by oligonucleotide mutagenesis of a chromosomal CYC1 T-A-T-A sequence. A loose spatial relationship also exists between the T-A-T-A sequences and the mRNA start sites, and this distance relationship varies from 100 to 60 base-pairs (+/- 15 base-pairs).
J Mol Biol 1986 Feb 05
PMID:Transcription initiation of the Saccharomyces cerevisiae iso-1-cytochrome c gene. Multiple, independent T-A-T-A sequences. 300 31

The globin gene family of Xenopus laevis comprises pairs of closely related genes that are arranged in two clusters, each pair of genes being co-ordinately and stage-specifically expressed. To get information on putative regulatory elements, we compared the DNA sequences and the chromatin conformation 5' to the co-ordinately expressed adult alpha-globin genes. Sequence analysis revealed a relatively conserved region from the cap site up to position -289, and further upstream seven distinct boxes of homology, separated by more diverged sequences or deletions/insertions. The homology boxes comprise 22 to 194 base-pairs showing 78 to 95% homology. Analysis of chromatin conformation showed that DNase I preferentially cuts the upstream region of both genes at similar positions, 5' to the T-A-T-A and the C-C-A-A-T boxes, only in chromatin of adult erythroblasts and erythrocytes, where adult globin genes are expressed, but not in chromatin of adult liver cells or larval erythrocytes, where these genes are silent. This suggests that cell- and stage-specific activation of these genes coincides with specific changes in chromatin conformation within the proximal upstream region. No difference was found in the nucleotide sequence within the DNase I hypersensitive region proximal to the adult alpha 1-globin gene in DNA from embryonic cells, in which this gene is inactive, and adult erythrocytes, expressing this gene.
J Mol Biol 1986 Mar 20
PMID:Conserved sequences and cell-specific DNase I hypersensitive sites upstream from the co-ordinately expressed alpha I- and alpha II-globin genes of Xenopus laevis. 301 54

The structure of the human gene encoding the aldolase B isozyme has been determined, including the sequence of 14,887 base-pairs. The 5'- and 3'-ends have been determined by S1 mapping. There is a single gene for this enzyme in humans that was determined from the sequence and restriction enzyme digestions of genomic DNA. The gene is 14,500 base-pairs long containing nine exons. In addition, 924 and 208 base-pairs of the 5'- and 3'-flanking region, respectively, have been determined. There is a high degree of conservation of nucleic acid sequence between aldolase B genes of human, rat and chicken. The conservation extends to untranslated and flanking regions, and includes the derived protein structures. In the 5'-flanking region there are several sequence elements that are conserved in vertebrate aldolase B genes in addition to the T-A-T-A and C-C-A-A-T boxes. These sequences may be involved in the co-ordinate and tissue-specific control of expression of this gene. Several possible polymorphic sites were detected in the sequence of the human gene which may be useful for linkage mapping of the human genome and diagnostic analysis of alleles in families with hereditary fructose intolerance.
Mol Biol Med 1986 Jun
PMID:Characterization of the human aldolase B gene. 301 56

The effect of hairpin (cruciform) size on the regulation of gene expression was investigated by cloning a series of palindromic sequences into the non-essential J-F intercistronic region of the bacteriophage phi X174 ins6 genome. Genetic stability of the insert sequence and its effect on the growth efficiency of the phage was used as an initial measure of the biological consequence of hairpin insertions. Multimers of increasing size of the BamHI linker sequence C-C-G-G-A-T-C-C-G-G were inserted into the PvuII site of the parental strain ins6. The largest hairpin that could be constructed and maintained in the phi X174 genome had a stem length of 22 base-pairs and a loop size of four nucleotides (linker tetramer). However, this structure proved to be disadvantageous to the phage and was rapidly deleted from its genome. Trimer inserts were more stable, but were eventually deleted also. Monomer and dimer inserts, though genetically stable, decreased the growth efficiency of the phage as judged by competitive growth experiments and measurements of burst size. The physical formation of these hairpins was shown by restriction digests of single-stranded DNA with BamHI and HpaII. We argue that these secondary structures form in vivo, at least in the single-stranded genome and the polycistronic mRNAs, and were responsible for the observed growth defects.
J Mol Biol 1986 May 20
PMID:Insertions of palindromic DNA sequences into the J-F intercistronic region of bacteriophage phi X174 interfere with normal phage growth. 301 60

One- and two-dimensional NMR studies at 300 MHz and 500 MHz were carried out on the two oligonucleotides d(C-C-G-A-A-T-T-C-G-G) and d(C-C-G-A-m6A-T-T-C-G-G) in aqueous solution. NMR spectra were observed at 10 mM sample concentration over the temperature range 273-368 K. Assignments are given of the base, H1', H2', H2", H3' and of some H4' resonances, based upon a combination of two-dimensional correlation spectra (COSY) and two-dimensional nuclear Overhauser effect spectra (NOESY); imino-proton resonances were assigned with the aid of a two-dimensional NOE experiment. Chemical shift vs temperature profiles were constructed in order to gain insight into the influence of N6-methylation of residue A(5) on the temperature-dependent conformational behaviour of the decamer and to determine thermodynamic parameters for the duplex-to-coil transition. The NOESY spectra, the imino-proton spectra and the shift profiles of the two compounds, under conditions where each forms a B-DNA-type duplex, are very similar. This is taken to indicate that the influence of N6-methylation of residue A(5) on the local structure of the duplex must be small. However, the temperature dependence of the (non-)exchangeable proton resonances of the two compounds reveals that methylation slows down the duplex-single-strand exchange. Furthermore, a thermodynamic analysis of the two compounds indicates that N6-methylation slightly decreases the stability of the duplex relative to the monomeric forms (Tm is reduced from 332 K down to 325 K at 10 mM sample concentration). Proton-proton couplings were obtained by means of one-dimensional and two-dimensional NMR experiments and were used in a conformational analysis of the sugar ring of each residue of the two compounds in the duplex form. The analysis indicated that all sugar rings display conformational flexibility in the intact duplex: population S-type sugar conformation ranges from 70% to 100%. A more refined analysis of the sugar rings of the parent compound revealed a sequence-dependent variation of the sugar geometry. This variation does not follow well the trend predicted by the Calladine/Dickerson sigma 3-sum rule [Dickerson, R. E. (1983) J. Mol. Biol. 166, 419-441; Calladine, C. R. (1982) J. Mol. Biol. 161, 343-352]; moreover the actual variations appear to be smaller in solution than those expected on the basis of known X-ray structures.
 ...
PMID:Influence of N6-methylation of residue A(5) on the conformational behaviour of d(C-C-G-A-A-T-T-C-G-G) in solution studied by 1H-NMR spectroscopy. 1. The duplex form. 302


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>