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61.
The structures of three complexes of human fructose-1,6-bisphosphatase (FB) with the allosteric inhibitor AMP and two AMP analogues have been determined and all fully refined. The data used for structure determination were collected at cryogenic temperature (110 K), and with the use of synchrotron radiation. The structures reveal a common mode of binding for AMP and formycine monophosphate (FMP). 5-Amino-4-carboxamido-1 beta-D-5-phosphate-ribofuranosyl-1H-imidazole (AICAR-P) shows an unexpected mode of binding to FB, different from that of the other two ligands. The imidazole ring of AICAR-P is rotated 180 degrees compared to the AMP and FMP bases. This rotation results in a slightly different hydrogen bonding pattern and minor changes in the water structure in the binding pocket. Common features of binding are seen for the ribose and phosphate moieties of all three compounds. Although binding in a different mode, AICAR-P is still capable of making all the important interactions with the residues building the allosteric binding pocket. The IC50 values of AMP, FMP, and AICAR-P were determined to be 1.7, 1.4, and 20.9 microM, respectively. Thus, the approximately 10 times lower potency of AICAR-P is difficult to explain solely from the variations observed in the binding pocket. Only one water molecule in the allosteric binding pocket was found to be conserved in all four subunits in all three structures. This water molecule coordinates to a phosphate oxygen atom and the N7 atom of the AMP molecule, and to similarly situated atoms in the FMP and AICAR-P complexes. This implies an important role of the conserved water molecule in binding of the ligand.  相似文献   
62.
Winder, W. W., H. A. Wilson, D. G. Hardie, B. B. Rasmussen,C. A. Hutber, G. B. Call, R. D. Clayton, L. M. Conley, S. Yoon, and B. Zhou. Phosphorylation of rat muscle acetyl-CoA carboxylase byAMP-activated protein kinase and protein kinase A. J. Appl. Physiol. 82(1): 219-225, 1997This studywas designed to compare functional effects of phosphorylation of muscleacetyl-CoA carboxylase (ACC) by adenosine 3,5-cyclicmonophosphate-dependent protein kinase (PKA) and by AMP-activatedprotein kinase (AMPK). Muscle ACC (272 kDa) was phosphorylated and thensubjected to sodium dodecyl sulfate-polyacrylamide gel electrophoresisfollowed by autoradiography. Functional effects of phosphorylation weredetermined by measuring ACC activity at different concentrations ofeach of the substrates and of citrate, an activator of the enzyme. Themaximal velocity(Vmax) and theMichaelis constants(Km) for ATP,acetyl-CoA, and bicarbonate were unaffected by phosphorylation by PKA.Phosphorylation by AMPK increased theKm for ATP andacetyl-CoA. Sequential phosphorylation by PKA and AMPK, first withoutlabel and second with label, appeared to reduce the extent of label incorporation, regardless of the order. The activation constant (Ka) forcitrate activation was increased to the same extent by AMPKphosphorylation, regardless of previous or subsequent phosphorylation by PKA. Thus muscle ACC can be phosphorylated by PKA but with noapparent functional effects on the enzyme. AMPK appears to be the moreimportant regulator of muscle ACC.

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63.
Tumour-infiltrating lymphocytes (TIL) and tumours from six patients with squamous cell carcinomas of the head and neck (SCCHN) were investigated. The six tumours all expressed major histocompatibility complex (MHC) class I antigens both in vivo and as tumor cell lines grown in vitro. In addition, the cancer cells either overexpressed the tumour-suppressor gene product p53 or harboured human papilloma virus 16/18 (HPV). The TIL were expanded in vitro in the presence of interleukin-2, immobilised anti-CD3 mAb and soluble anti-CD28 mAb. Expanded TIL cultures contained both CD4+and CD8+T cells, but generally contained few CD56+CD3-cells of the natural killer (NK) phenotype. CD8+T cells dominated the individual TIL cultures from five of the six patients and showed significant autologous tumour cell lysis. In TIL cultures derived from four of these tumour-reactive TIL cultures, killing could be partially blocked by an anti-MHC class I mAb. TIL cultures reacting with autologous tumour cells also showed strong TCR/CD3-redirected cytotoxicity when assayed against hybridoma cells expressing anti-TCR/CD3 mAb as well as natural-killer(NK)-like activity. A number of TIL cultures devoid of autologous tumour cell lysis were capable of lysing the natural-killer(NK)-sensitive K562 cell line suggesting that the SCCHN cells themselves are resistant to NK-like lysis. In conclusion, TIL cultures from head and neck carcinomas contain T cells which, upon expansion in vitro, can lyse autologous tumour cells in a MHC-class-I-restricted fashion. Thus, the results of the present study document that carcinomas of the head and neck in some patients are infiltrated by cytotoxic T cell precursors potentially capable of rejecting the autologous tumour.  相似文献   
64.
The extent of myocardial accumulation of tocainide, administered as single enantiomers and as well as racemate, was determined in the isolated, spontaneous beating rabbit heart. The heart was retrogradely perfused at a constant rate and fractions of the perfusate were collected during and after infusion. Kinetic parameters for myocardial accumulation and disposition of tocainide were indirectly determined from drug concentration/time course in the outflow perfusate. No stereoselectivity in myocardial accumulation was observed. A two compartment model with mean half-lives for distribution and elimination of 0.60 and 3.78 min, respectively, was fitted to the accumulation and disposition data. At steady-state, tocainide enantiomers were accumulated about three times in the myocardium relative to the perfusion liquid. © 1995 Wiley-Liss, Inc.  相似文献   
65.
Summary Acetolactate decarboxylase activity has been detected among three genera, nine species and 263 strains of lactic acid bacteria tested in the course of a screening for acetolactate decarboxylases amenable for use in brewing as maturation aid. Streptococcus diacetylactis strain FD-64-D was found to generate a decarboxylase exhibiting a satisfactory activity and an excellent stability at the pH prevailing in beer and wort. This decarboxylase could not be solubilized but enzymatically active, freeze-dried cells were effective for satisfactory flavour maturation of beer although difficulties were encountered during attempts to remove the applied cell material by filtration of the beer. Lactobacillus casei DSM 2547 was likewise found to produce a decarboxylase exhibiting a satisfactory activity and stability at the low pH of beer and which, in addition, was readily solubilized. A method has been developed for pilot scale production of preparations of this decarboxylase suitable for use in brewing.Abbreviations DSM Deutsche Sammlung von Microorganismen - EDTA Ethylene diaminetetra-acetic acid  相似文献   
66.
Fe-starved ciliates Tetrahymena thermophila cease to multiply at Fe(III) concentrations above 10 microM in a synthetic nutrient medium lacking a good iron chelator such as citrate. If, however, the Fe(III) concentration is gradually increased over a series of subcultivations the cells will tolerate up to 300 microM Fe(III). Our experiments rule out the possibility of genetic selection of Fe-tolerant clones and suggest a physiological type of adaptation.  相似文献   
67.
The nucleotide sequence of a 1082 bp fragment from the pea (Pisum sativum) chloroplast genome is presented. This fragment contains genes for tRNAGlu, tRNATyr and tRNAAsp as well as an open reading frame (ORF) of 91 codons on one strand and two ORFs of 52 and 59 codons on the complementary strand. The tRNAAsp gene is located entirely within the ORF of 91 codons. The first 366 bp of the fragment correspond to 376 bp at one end of a recently published (1) sequence from the broad bean (Vicia faba) chloroplast genome. These regions contain the tRNAGlu and tRNATyr genes, which are identical and separated by 60 bp in both species. These two genes are probably cotranscribed. The intergenic regions in the corresponding segments from the two species are, except for a 10 bp deletion in the pea sequence, 94% homologous.  相似文献   
68.
An elderly man had a 10-year history of multiple pulmonary nodules that he had refused to have investigated. He died of a ruptured abdominal aortic aneurysm. At autopsy the nodules were shown to consist of amyloid. There was no evidence of systemic amyloidosis.  相似文献   
69.
In Bombyx mori oocytes the synaptonemal complexes are retained in modified form from pachytene to metaphase I. At the end of pachytene the length and width of the lateral components of the complex increase, whereafter the complexes become compacted during later stages of the meiotic prophase. Ultimately, at metaphase I the modified synaptonemal complexes of individual bivalents fuse to form a more or less continuous sheet between the homologous chromosomes. This sheet corresponds to the structure historically known as the elimination chromatin. It is concluded that in the absence of crossing over and chiasma formation in Bombyx mori females the retainment and subsequent modification of the synaptonemal complex has evolved as a substitute mechanism to ensure regular disjunction of the bivalents.  相似文献   
70.
Sprout inhibition of onion bulbs can be effectively accomplished by low doses of radiation [2,3]. However, wholesomeness data on irradiated onions, particularly with respect to their mutagenic activity, are still insufficient for evaluation [6]. Therefore we examined the mutagenic activity of irradiated onions in bacterial systems. Because onion bulbs contain a considerable amount of free amino acids, we used indicator strains carrying the marker for mutagenicity other than the amino acid requirement.In this paper we describe the results on irradiated onions. We used tests with solid and liquid media, assaying for the streptomycin (SM) dependence in a strain having a tetracycline (TC)-resistance factor, as well as DNA repair tests using two sets of indicator strains.  相似文献   
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