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)

In Saccharomyces cerevisiae, argB and argC define two adjacent and complementing loci, with mutants defective in two consecutive steps of arginine biosynthesis: N-acetylglutamate kinase (AG-kinase) and N-acetylglutamyl-phosphate reductase (AGPreductase). These enzymic activities are readily separated by ammonium sulfate fractionation or Sephadex G-200 chromatography. This suggests that each activity is carried in vivo by a different protein. The synthesis of the two enzymes is coordinately regulated, with an 85-fold difference in specific activities between fully repressed and fully derepressed cells. Missence mutations of the argB locus are defective in AGkinase only. Nonsense mutations in the argB locus are defective in both activities. Missense and nonsense mutations in the argC locus are defective in AGPreductase, with a few alleles also showing a reduced level of AGkinase. These data are best explained by assuming that argB and argC are two genes transcribed as a single messenger from argB to argC. This messenger produces in vivo two distinct proteins corresponding to the argB and argC gene products, either because translation can be initiated at the beginning of both genes, or because a large polypeptide is specifically cut in vivo to yield the gene products of argB and argC.
Mol Gen Genet 1979 Jan 11
PMID:Organization and expression of a two-gene cluster in the arginine biosynthesis of Saccharomyces cerevisiae. 22 May 8

The two tryptophan residues in ovine and bovine prolactins were modified by reaction with 2-nitrophenylsulfenyl chloride in 75% formic acid. These derivatives exhibited an important loss of receptor affinity (less than 1% of the native hormones) to a rabbit mammary gland preparation. To a lesser degree, they also lost their binding affinity to specific guinea pig antibodies as detected by radioimmunoassay. The chemical modifications induced a change in the folding of the polypeptide chain, which in itself could be partly or totally responsible for the loss of biological or binding activities. This conformational change has been analyzed by circular dichroism and by prediction of secondary structures from the amino acid sequence using the method of Garnier et al. (Garnier, J., Osguthorpe, D.J. and Robson, B. (1978) J. Mol. Biol. 120, 97--120). The comparison of predicted prolactin and somatotropin structures revealed almost identical alpha-helix, turns and coil regions with an overall content of 67% alpha-helix, 5% beta-sheet, 17% turn and 11% of aperiodic structures. These values were close to those obtained from circular dichroism. The conformational change of the chemically modified hormones as compared to native folding, can be described as a partial loss of alpha-helical structure and an increase in beta-sheet content.
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PMID:Receptor binding and conformational properties of bovine and ovine prolactins after chemical modification of the two tryptophan residues. 22 37

The mechanisms of enzymic inactivation of thyrotropin-releasing hormone, luteinizing hormone-releasing hormone and somatostatin, the three fully-characterized hypothalamic regulatory hormones, and the possible physiological significance of the peptidases in neuroendocrine control has been reviewed. Application of the criteria of enzyme location (at the sites of biosynthesis, release, action, elimination and excretion), appropriate biochemical characteristics of the enzymes and changes in enzyme activity in physiological circumstances all suggest that the peptidases can contribute to the mechanisms controlling the hypothalamic hormones' release and actions. Besides their physiological function, the enzymes may also be directly involved in certain pathological conditions. There is evidence to indicate that the enzymes degrading the regulatory hormones may participate in the process of hormone activation as well as inactivation. A continuing investigation of the peptidases may lead to a better understanding of the established endocrine and other putative functions of these hypothalamic polypeptide hormones.
Mol Cell Endocrinol 1979 Apr
PMID:Mechanisms of inactivation of hypothalamic regulatory hormones. 22 39

The nucleic acid binding and unwinding properties of wild-type Escherichia coli ribosomal protein S1 have been compared to those of a mutant form and a large trypsin-resistant fragment, both reported recently [J. Mol. Biol. 127, 41-45 (1979) and J. Biol. Chem. 254, 4309-4312 (1979). The mutant (m1-S1) contains 77% and the fragment (S1-F1) 66% of the polypeptide chain length (approximately 600 amino acid residues) of protein S1. The mutant is active in protein synthesis in vitro; the fragment, although retaining one or more of the functional domains of S1, is inactive in protein synthesis. We find that m1-S1 is is almost as effective as S1 in binding to poly(rU), phage MS2 RNA and simian virus 40 (SV40) DNA, and in unfolding poly(rU) and the helical structures present in MS2 RNA and phi X174 viral DNA. S1-F1, however, binds to poly(rU) and denatured SV40 DNA, but not to MS2 RNA. It unfolds neither poly(rU), nor the residual secondary structure of MS2 RNA or phi X174 viral DNA. Thus, there appears to be a correlation between the loss in ability of S1 to unwind RNA and the loss in its ability to function in protein synthesis.
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PMID:Nucleic acid binding and unfolding properties of ribosomal protein S1 and the derivatives S1-F1 and m1-S1. 23 41

Columns containing ribosomes translating poly(U) covalently bound with cellulose (solid-phase translating system) were used to study translocation in ribosomes. It is shown that the passing of elongation factor G (EF-G) with the non-cleavable analog of GTP (GMP-PCP) through a column containing pre-translocated ribosomes results in the increase of competence for puromycin (i. e. to the transition of pre-translocated peptidyl-tRNA into the post-translocated state) just as in the case of the passing of EF-G with GTP. On the other hand, it is shown that the passing of EF-G with GMP-PCP through a column with pre-translocated ribosomes makes them capable of binding the next aminoacyl-tRNA (i. e. leads to the vacation of the ribosomal A-site). Thus, by means of the two independent tests it is shown that EF-G-promoted translocation in the ribosome can proceed without GTP hydrolysis. On the basis of the data obtained, a controlled step-wise elongation of polypeptide with the participation of EF-G without GTP cleavage has been carried out in the solid-phase column system of translation.
Mol Biol (Mosk)
PMID:[Translocation in ribosomes induced by elongation factor G without cleavage of GTP. Study using a solid phase translation system in columns]. 25 70

The A isozyme of yeast hexokinase (ATP:D-hexose 6-phosphotransferase, EC 2.7.1.1) crystallized as a complex with glucose has a conformation that is dramatically different from the conformation of the B isozyme crystallized in the absence of glucose. Comparison of the high-resolution structures shows that one lobe of the molecule is rotated by 12 degrees relative to the other lobe, resulting in movements of as much as 8 A in the polypeptide backbone and closing the cleft between the lobes into which glucose is bound. The conformational change is produced by the binding of glucose (R.C. McDonald, T.A. Steitz, and D.M. Engelman, unpublished data) and is essential for catalysis [Anderson, C.M., Stenkamp, R.E., McDonald, R.C. & Steitz, T.A. (1978) J. Mol. Biol. 123, 207-219] and thus provides an example of induced fit. The surface area of the hexokinase A-glucose complex exposed to solvent is smaller than that of native hexokinase B. By using the change in exposed surface area to estimate the hydrophobic contribution to the free energy changes upon glucose binding, we find that the hydrophobic effect alone favors the active conformation of hexokinase in the presence and absence of sugar. The observed stability of the inactive conformation of the enzyme in the absence of substrates may result from a deficiency of complementary interactions within the cavity that forms when the two lobes close together.
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PMID:Glucose-induced conformational change in yeast hexokinase. 28 94

Electron microscopic techniques have been used to reveal two classes of subunits of tubulin in ordered arrays. Presumably the two classes correspond to the alpha and beta polypeptide chains of tubulin that have been distinguished by chemical criteria. The two types of subunits alternate along individual protofilaments in microtubules, microtubule-precursor sheets, and extended zinc-tubulin sheets. The resolution of the two types of polypeptide chains is achieved by improved negative staining methods which produce micrographs with layer lines at 28 A(-1) and 84 A(-1) in optical or computed transforms, in addition to the layer lines at 21 A(-1) and 42 A(-1) described previously [Crepeau, R. H., McEwen, B., Dykes, G. & Edelstein, S. J. (1977) J Mol. Biol. 116, 301-315]. In microtubules or microtubule-precursor sheets, adjacent protofilaments are staggered by about 10 A, but parallel, in the sense that the alpha-beta vector points in the same direction for all of the protofilaments of the microtubule. However, for the sheets assembled in the presence of zinc, adjacent protofilaments are staggered by about 21 A and oriented in an antiparallel arrangement with alternate protofilaments related by a 2-fold screw axis. The antiparallel alignment of the protofilaments in the zinc-tubulin sheets accounts for their planarity (no tubular structures are found in the presence of moderate concentrations of zinc), since the intrinsic curvature found with parallel alignment of protofilaments in the absence of zinc would be cancelled by the antiparallel arrangement.
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PMID:Differences in alpha and beta polypeptide chains of tubulin resolved by electron microscopy with image reconstruction. 28 10

Different Escherichia coli mutants auxotrophic for polyamines were studied in order to investigate the relationships among polypeptide synthesis in cell-free systems, ribosomal distribution profiles and endogenous polyamine pools. The in vitro protein synthetic activity and the polyribosomal content were reduced in extracts from putrescine-starved cells of the double mutans MA 255 and MA 261, but not in the arginine-conditional auxotroph DK 6. Putrescine addition to the cultures of all these strains previously starved for polyamines, provoked a shift towards monomers in the equilibrium involving ribosomal particles. Concomitant changes in the intracellular levels of polyamines were observed: putrescine and spermidine increased markedly, and cadaverine disappeared.
Mol Cell Biochem 1977 Jul 05
PMID:Polyamines and protein synthesis: studies in various polyamine-requiring mutants of Escherichia coli. 32 22

In merodiploid cells containing a double dose of structural genes of RNA polymerase subunits--rpoB and rpoC--the rate of synthesis of beta- and beta'-subunits is 2 times higher than in haploid cells. Missense mutation rpoC1 (tsX) in the beta'-polypeptide gene accelerates the synthesis of both beta- and beta'-subunits, particularly at a nonpermissive temperature. When rpoB-rpoC operon containing mutation rpoC1 is duplicated no dose effect of these genes is observed. In the heterozygous state mutation rpoC1 produces almost no accelerating effect on the synthesis of RNA polymerase subunits i. e. is recessive with respect to the wild allele of rpoC. In the presence of rifampicin the synthesis of RNA polymerase subunits in a sensitive wild-type strain is stimulated 6-fold, the same effect is observed with cells carrying mutation rpoC1, the latter, however, itself accelerates the synthesis of these subunits 3-fold. Thus the effects of rifampicin and the mutation are synergistic indicating that these factors act independently. Similar data have also been obtained with rifampicin-treated cells of rpoB22 amber-mutant. In UV-irradiated cells, amino acid incorporation into beta- and beta'-subunits declines more rapidly than into the total protein. When either irradiated or non-irradiated cells are infected with a transducing phage lambdarifd-47 which carries rpoB gene, the synthesis of beta-proceeds at a higher rate. Irradiation of bacteria before the infection (500 erg/mm2) results in 6.5-fold acceleration of the synthesis induced by subsequent infection with lambdarifd-47 as compared to non-infected non-irradiated cells; the fraction of newly formed beta-polypeptide with respect to total protein grows 20-fold in this case. The data are considered with regard to the possible mechanisms of regulation of synthesis of RNA polymerase subunits.
Mol Biol (Mosk)
PMID:[Effect of several factors on synthesis of RNA-polymerase subunits by Escherichia coli K12]. 34 6

An ampicillin transposon Tn901 was used as a "mutagen" to isolate insertion mutants of the bacteriocinogenic plasmid Clo DF13. By combining the obtained heteroduplex and restriction maps of the Clo DF13::Tn901 plasmids (van Emboden et al., 1977b) with their polypeptide pattern in minicells, we were able to map five genes on the Clo DF13 genome. These five genes designated A (cloacin gene), B, C, D, and G cover 55% of the coding capacity of Clo DF13 DNA. Since integration of Tn901 within these five genes did not result in a loss of the Clo DF13::Tn901 plasmids involved, it is suggested that these genes do not play an essential role in the maintenance of these plasmid insertion mutants. In addition, the described methods allowed us to indicate the initiation site of cloacin synthesis and to propose the counter-clockwise direction of transcription of the cloacin gene. The Tn901 DNA directed the synthesis of at least three polypeptides one of which is shown to be a TEM-1 beta-lactamase.
Mol Gen Genet 1978 Mar 20
PMID:Genetic map of the bacteriocinogenic plasmid CLO DF13 derived by insertion of the transposon Tn901. 34 43


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