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

The present studies were directed to determine whether peptide histidine isoleucine (PHI) affects expression of the gastrin and somatostatin genes and whether such effects may be functionally linked. In separate experiments, the effects of PHI on medium gastrin and somatostatin concentrations, the incorporation of 35S-labelled amino acids into newly synthesized gastrin and somatostatin, and steady state gastrin and somatostatin mRNA were determined. PHI inhibited basal expression of the gastrin gene at all levels examined, while no significant effect on basal somatostatin gene expression could be detected. PHI also decreased carbachol-stimulated antral gastrin release and simultaneously increased somatostatin release. However, in contrast to its structural analogues, secretin and gastric inhibitory peptide, the immunoneutralization of endogenous somatostatin by the administration of specific antibodies did not affect significantly the capacity of PHI to inhibit gastrin release into the culture medium stimulated by carbachol. The results of these studies indicate that PHI exerts a physiological inhibitory effect on antral gastrin cells and that this inhibition may occur at several steps along the biosynthetic pathway. In addition, unlike its structural analogues, PHI inhibition of carbachol-stimulated gastrin release is not functionally linked to its stimulatory effects on somatostatin release.
Mol Cell Endocrinol 1992 Mar
PMID:The effects of peptide histidine isoleucine on antral gastrin and somatostatin. 135 64

The mutant T4 phage lysozyme in which isoleucine 3 is replaced by proline (I3P) crystallizes in an orthorhombic form with two independent molecules in the asymmetric unit. Relative to wild-type lysozyme, which crystallizes in a trigonal form, the two I3P molecules undergo large hinge-bending displacements with the alignments of the amino-terminal and carboxy-terminal domains changed by 28.9 degrees and 32.9 degrees, respectively. The introduction of the mutation, together with the hinge-bending displacement, is associated with repacking of the side-chains of Phe4, Phe67 and Phe104. These aromatic residues are clustered close to the site of the mutation and are at the junction between the amino and carboxyl-terminal domains. As a result of this structural rearrangement the side-chain of Phe4 moves from a relatively solvent-exposed conformation to one that is largely buried. Mutant I3P also crystallizes in the same trigonal form as wild-type and, in this case, the observed structural changes are restricted to the immediate vicinity of the replacement. The main change is a shift of 0.3 to 0.5 A in the backbone of residues 1 to 5. The ability to crystallize I3P under similar conditions but in substantially different conformations suggests that the molecule undergoes large-scale hinge-bending displacements in solution. It is also likely that these conformational excursions are associated with repacking at the junction of the N-terminal and C-terminal domains. On the other hand, the analysis is complicated by possible effects of crystal packing. The different I3P crystal structures show substantial differences in the binding of solvent, both at the site of the Ile3-->Pro replacement and at other internal sites.
J Mol Biol 1992 Oct 05
PMID:Structure of a hinge-bending bacteriophage T4 lysozyme mutant, Ile3-->Pro. 140 94

The time required for transcription of the lacZ gene in Escherichia coli was determined during exponential growth and under conditions, when the bacterium was exposed to partial isoleucine starvation. To do this, RNA was extracted from the cells at 10 s intervals following induction and quantified by Northern hybridization with probes complementary to either the beginning or the end of the lacZ mRNA. The time lag between inducer addition and the appearance of a hybridization signal at the 'late' probe represents the transit time for RNA polymerase on the lacZ gene, and this parameter and the known length of the transcribed sequence were used to calculate the lacZ mRNA chain growth-rate. The transcription elongation rate was c. 43 nucleotides s-1 during exponential growth and decreased abruptly to c. 20 nucleotides s-1 in a relA+ strain after the onset of isoleucine starvation, when massive concentrations of guanosine tetraphosphate (ppGpp) accumulated in the cells. The starvation condition did not affect initiation of transcription at the lac-promoter, but a substantial fraction of the initiated lacZ mRNA chains was never completed. For the rel+ strain the polarity was moderate, since c. 25% of the initiated lacZ mRNA' chains were continued into full-length mRNAs, but for the relA strain the polarity was so strong that no completed lacZ mRNA could be detected. The protein chain elongation rates decreased from 13 amino acids (aa) s-1 in the unperturbed growth phase to approximately 6 as s-1, when the cells starved for isoleucine. In combination, these results suggest that ppGpp plays a major role in maintaining the coupling between transcription and translation during the downshift by inhibiting mRNA chain elongation. The implications of this result for the control of stable RNA synthesis during the stringent response are discussed.
Mol Microbiol 1992 Aug
PMID:Decreasing transcription elongation rate in Escherichia coli exposed to amino acid starvation. 140 59

In Rhizobium meliloti the NifA protein plays a central role in the expression of genes involved in nitrogen fixation. The R. meliloti NifA protein has been found to be oxygen sensitive and therefore acts as a transcriptional activator only under microaerobic conditions. In order to generate oxygen-tolerant variants of the NifA protein a plasmid carrying the R. meliloti nifA gene was mutagenized in vitro with hydroxylamine. About 70 mutated nifA genes were isolated which mediated up to 12-fold increased NifA activity at high oxygen concentrations. A cloning procedure involving the combination of DNA fragments from mutated and wild-type nifA genes allowed mapping of the mutation sites within the central part of the nifA gene. For 17 mutated nifA genes the exact mutation sites were determined by DNA sequence analysis. It was found that all 17 mutated nifA genes carried identical guanosine--adenosine mutations resulting in a methionine--isoleucine exchange (M217I) near the putative nucleotide binding site within the central domain. Secondary structure predictions indicated that the conformation of the putative nucleotide binding site may be altered in the oxygen-tolerant NifA proteins. A model is proposed which assumes that at high oxygen concentrations the loss of activity of the R. meliloti NifA protein is due to a conformational change in the nucleotide binding site that may abolish binding or hydrolysis of the nucleotide. Such a conformational change may be blocked in the oxygen-tolerant NifA protein, thus allowing interaction with the nucleotide at high oxygen concentrations.
Mol Gen Genet 1992 Sep
PMID:A defined amino acid exchange close to the putative nucleotide binding site is responsible for an oxygen-tolerant variant of the Rhizobium meliloti NifA protein. 140 89

The ILV1 gene of Saccharomyces cerevisiae encodes the first committed step in isoleucine biosynthesis and is regulated by general control of amino acid biosynthesis. Deletion analysis of the ILV1 promoter revealed a GC-rich element important for the basal level expression. This cis-acting element, called ILV1BAS, is functional independently of whether GCN4 protein is present. Furthermore, unlike the situation at HIS4, the magnitude of GCN4-mediated derepression is independent of ILV1BAS. The element has homology to the consensus REB1-binding sequence CGGGTARNNR. Gel retardation assays showed that REB1 binds specifically to this element. We show that REB1-binding sites normally situated in the SIN3 promoter and in the 35S rRNA promoter can substitute for the ILV1 REB1 site. Furthermore, a SIN3 REB1 site containing a point mutation that abolishes REB1 binding does not support ILV1 basal level expression, suggesting that binding of REB1 is important for the control of ILV1 basal level expression. Interestingly, an ABF1-binding site can also functionally replace the ILV1 REB1-binding site. A mutated ABF1 site that displays a very low affinity for ABF1 does not functionally replace the ILV1 REB1 site. This suggests that ABF1 and REB1 may have related functions within the cell. Although the REB1-binding site is required for the ILV1 basal level expression, the site on its own stimulates transcription only slightly when combined with the CYC1 downstream promoter elements, indicating that another ILV1 promoter element functions in combination with the REB1 site to control high basal level expression.
Mol Cell Biol 1992 Dec
PMID:A REB1-binding site is required for GCN4-independent ILV1 basal level transcription and can be functionally replaced by an ABF1-binding site. 144 83

Hereditary cerebral hemorrhage with amyloidosis, Dutch type (HCHWA-D) (or familial cerebral amyloid angiopathy) and familial Alzheimer's disease (FAD) share several properties. Both are autosomal dominant forms of cerebral amyloidosis characterized by beta-amyloid (A beta) deposition. In HCHWA-D the A beta is predominantly found in blood vessels and in early parenchymal plaques, whereas in AD parenchymal A beta deposits in the form of senile plaques and neurofibrillary tangles are a more prominent finding. Point mutations in the amyloid precursor protein (APP) have recently been described, in both conditions. A G to C transversion at codon 618 (extracellular portion of APP695), producing a single amino acid substitution of glutamine instead of glutamine acid, occurs in HCHWA-D; whereas mutations at codon 642 in the intramembrane region of APP695 (phenylalanine, isoleucine, or glycine instead of valine) are associated with early onset FAD. This suggests that the site of particular mutations in the APP gene and the type of amino acid substitution in the APP holoprotein are more important in determining clinicopathological phenotype and age at which A beta is deposited. Thus FAD and HCHWA-D can be regarded as two sides of the same coin.
Mol Neurobiol 1992
PMID:Molecular biology of Alzheimer's amyloid--Dutch variant. 146 89

We have previously shown that resistance to the beta-lactam mecillinam in Escherichia coli can be brought about by a high ppGpp pool, as observed under conditions of partial amino acid starvation and RelA-dependent induction of the stringent response. We show here that our E. coli wild-type strain, which is sensitive to mecillinam on minimal glucose plates, becomes resistant in the presence of L-leucine or L-serine (or cysteine, which inactivates the antibiotic). The resistance, which is not a transient effect and does not depend on the physiological state of the cells when plated, is specific for mecillinam and is reversed by the presence of isoleucine and valine in the medium. At least in the case of serine, the resistance is RelA-dependent. We conclude that the presence of leucine and serine in the growth medium cause partial starvation for isoleucine/valine, leading to induction of the stringent response and concomitant resistance to mecillinam.
Mol Gen Genet 1992 Nov
PMID:Leucine and serine induce mecillinam resistance in Escherichia coli. 146 98

Influence of rare codons upon gene expression in E. coli was investigated. The chimeric gene was created combining CAT gene and a fragment of the gene, encoding for alpha-domain of beta-galactosidase. The synthetic oligonucleotides were inserted in different parts of the chimeric gene. The constructed synthetic oligonucleotides encoded the same amino acid sequences and contained arginine codons AGG, AGA and CGT in various combinations. It was shown that the presence of rare arginine codons AGG and AGA in the template and their mutual arrangement significantly influence the level of gene expression. At the same time the presence of leucine, isoleucine, glycine and proline rare codons does not cause such an effect. Translation of AGGAGG and AGAAGA sequences was found to lead to the formation of a considerable amount of polypeptides of incomplete length. It was shown that the presence of such a cluster of rare codons effects on the length of specific mRNA.
Mol Biol (Mosk)
PMID:[Rare codons and gene expression in Escherichia coli]. 147 Jan 73

The partial amino acid sequences of the gamma chains of the bovine IgG2a(A1) and IgG2a(A2) allotypes were determined. Sequence differences were found in the CH1 domain, the hinge region, and the CH3 domain. The hinge regions displayed only 71.4% similarity and all of the differences were of a radical nature. The A2 hinge has isoleucine instead of serine at 229, histidine for asparagine at 235, proline for histidine at 238, and cysteine instead of proline in position 234; the latter has the potential for forming an additional interheavy chain disulphide bridge. The occurrence of such a bridge could explain the presence of a pepsin fragment consisting of the hinge region and the Fc. A corresponding fragment is not obtained with the A1 allotype. Both allotypes have a shortened hinge region and a truncated CH2 domain. This feature is characteristic of all reported sequences of IgG2 proteins but not IgG1 in cattle and the goat. This structural feature may be important in subclass-specific recognition by Fc gamma receptors in ruminants. A surprising discovery was the occurrence of five substitutions in the CH3 domain of the IgG2a(A2) in comparison with the A1, which are shared with the CH3 of IgG1. These permit the occurrence of isoallotypic determinants and can explain the difficulty encountered in preparing A2-specific antisera during which adsorption with IgG1 is a routine procedure. The primary sequence data we report confirm the presence of major structural differences between the A allotypes of cattle that was suggested by previous work. The sequence of the A1 allotype most closely agrees with the two IgG2 sequences deduced from their nucleotide sequences whereas the sequence differences in the hinge and C-terminal CH3 make IgG2a(A2) unique. The structural differences between allotypes could have major consequences for such biological activities as phagocytosis, transepithelial transport, lymphocyte and complement activation.
Mol Immunol 1992 Sep
PMID:The heterogeneity of bovine IgG2--V. Differences in the primary structure of bovine IgG2 allotypes. 149 1

The small subunit of ribulose 1,5-bisphosphate carboxylase/oxygenase (EC 4.1.1.39) in the French bean Phaseolus vulgaris L. is encoded by a small gene family consisting of a minimum of three members. Three small subunit genes (rbcS genes) represented in a light-grown primary leaf cDNA library were characterised by sequencing two cDNAs which were full-length and one which was deficient in part of the sequence encoding the transit peptide. The cDNA clones are identical in their coding sequences, for both the transit peptide and the mature polypeptide, but divergent in their untranslated sequences. The derived amino acid sequence is very similar to that reported for other species, although the first amino acid of the mature polypeptide is isoleucine, which differs from the methionine found in all other higher plant rbcS genes. Surprisingly, one of the cDNA clones contains two introns, which are at positions conserved in rbcS genes from other species. It is concluded that this cDNA resulted from the cloning of an unprocessed transcript. Alternative polyadenylation sites are found for two of the genes. Expression of the rbcS genes in the primary leaves is stimulated by light, although transcripts can readily be detected in dark-grown leaves. Expression is also organ-specific, as in other species. The frequency of cDNA clones in the library indicates that the different genes show quantitative differences in expression and S1 nuclease analysis suggests that individual rbcS genes are photoregulated.
Plant Mol Biol 1992 Feb
PMID:Genes encoding the small subunit of ribulose 1,5-bisphosphate carboxylase/oxygenase in Phaseolus vulgaris L.: nucleotide sequence of cDNA clones and initial studies of expression. 153 29


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