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11.
The role of the pro-sequence in the processing and secretion of the thermolysin-like neutral protease from Bacillus cereus 总被引:5,自引:0,他引:5
The Bacillus cereus cnp gene coding for the thermolysin-like neutral protease (TNP) has been cloned, sequenced, and expressed in Bacillus subtilis. The protease is first produced as a pre-pro-protein (M(r) = 61,000); the pro-peptide is approximately two-thirds of the size of the mature protein. The pro-sequence has been compared with those of six other TNPs, and significant homologies have been found. Additionally, the TNP pro-sequences are shown to be homologous to the pro-sequence of Pseudomonas aeruginosa elastase. A mutant has been constructed from cnp, in which 23 amino acids upstream from the pro-protein processing site have been deleted. This region has no homologous analogue in any of the other TNP pro-sequences. The deletion results in a delay of six to eight hours in detection of active protease in the growth medium, as well as a 75% decrease in maximum protease production. N-terminal analysis of the mutant mature protein demonstrates that the processing site is unaltered by the pro-sequence deletion. The deletion must, therefore, modulate the kinetics of processing and/or secretion of the pro-protein. 相似文献
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M C Hirst K Rack Y Nakahori A Roche M V Bell G Flynn Z Christadoulou R N MacKinnon M Francis A J Littler 《Nucleic acids research》1991,19(12):3283-3288
The fragile X syndrome is a common cause of mental retardation and is associated with a fragile site at Xq27.3 (FRAXA). Recently, evidence has been presented for the role of methylation and genomic imprinting in the expression of the disease. We have identified a site of methylation in patients by long range restriction mapping of the region. In this paper we present a YAC contig of this area, localise the CpG sequences which are methylated, and show by in situ hybridisation that the site of fragility lies within this region. 相似文献
15.
Human alpha 2-macroglobulin (alpha 2M) of Mr approximately 720,000 is a proteinase inhibitor whose four identical subunits are arranged to form two adjacent inhibitory units. At present, the spatial arrangement of the two subunits which form one inhibitory unit (the functional "half-molecule") is not known. Treatment of alpha 2M with either 0.5 mM dithiothreitol (DTT) or 4 M urea results in dissociation of the native tetramer into two half-molecules of Mr approximately 360,000. These half-molecules retain trypsin inhibitory activity, but in each case, the reaction results in reassociation of the half-molecules to produce tetramers of Mr approximately 720,000. However, when reacted with plasmin, the preparations of half-molecules have different properties. DTT-induced half-molecules protect the activity of plasmin from inhibition by soybean trypsin inhibitor (STI) without reassociation, while urea-induced half-molecules show no ability to protect plasmin from reaction with STI. High-performance size-exclusion chromatography and sedimentation velocity ultracentrifugation studies were then used to estimate the Stokes radius (Re) of alpha 2M and both DTT- and urea-induced half-molecules of alpha 2M. The Re of tetrameric alpha 2M was 88-94 A, while that of DTT-induced half-molecules was 57-60 A and urea-induced half-molecules 75-77 A. These results demonstrate that DTT- and urea-induced half-molecules have fundamentally different molecular dimensions as well as inhibitory properties. The hydrodynamic data suggest that the urea-induced half-molecule is a "rod"-like structure, although it is not possible to predict the three-dimensional structure of this molecule with the available data.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
16.
M Rahmatullah J M Jilka G A Radke T E Roche 《The Journal of biological chemistry》1986,261(14):6515-6523
Studies were conducted on four pyruvate dehydrogenase kinase-containing fractions: purified pyruvate dehydrogenase complex, the dihydrolipoyl transacetylase-protein X-kinase subcomplex (E2.X.K), a kinase fraction (K fraction) prepared from the E2.X.K subcomplex, and a kinase fraction generated by limited trypsin-digestion of E2.X.K. We characterized the gel electrophoresis properties of dissociated subunits (one-dimensional and two-dimensional), the catalytic and ATP binding properties of kinase-containing fractions, and the subunit requirements for kinase binding to and being activated by the transacetylase-protein X subcomplex (E2.X). A significant portion of protein X was retained with the transacetylase core following release of virtually all the kinase. The K fraction had four major bands separated by sodium dodecyl sulfate-slab gel electrophoresis which corresponded to the dihydrolipoyl dehydrogenase, protein X, the trypsin-resistant catalytic subunit of the kinase and a chymotrypsin-resistant subunit which had a high pI and comigrated in one-dimensional systems with the chymotrypsin-sensitive alpha-subunit of the pyruvate dehydrogenase component. While purified kidney complex contained only about three molecules of kinase (determined by [14C]ATP binding), one molecule of E2.X subcomplex activated a large number (greater than 15) molecules of kinase associated with the protein X-containing K fraction. Sephadex G-200 chromatography of the K fraction in the presence of dithiothreitol led to coelution of protein X and kinase subunits. Limited trypsin digestion converted the transacetylase into subdomains and cleaved protein X and the high pI subunit of the kinase. Under those conditions, the intact catalytic subunit of the kinase did not bind to the large inner domain of the transacetylase but could be activated by untreated E2.X subcomplex. Thus, binding of the catalytic subunit of the kinase and its activation by E2.X required either protein X or the lipoyl-bearing outer domain of the transacetylase. In combination, our results suggest that protein X serves to anchor the kinase to the core of the complex. 相似文献
17.
Micrococcal nuclease digestion and light scattering are used to compare native chromatins with various histone H1[0] contents. The experimental data show that the higher the H1[0] content, the greater the ability to form compact structures with increasing ionic strength, and the lower the DNA accessibility to micrococcal nuclease. On the contrary, reconstituted samples from H1-depleted chromatin and pure individual H1 fractions behave in such a way that samples reconstituted with pure H1 degree give rise to a looser structure, more accessible to nuclease than samples reconstituted with H1-1. This contradiction suggests that the effect of H1o on chromatin structure must originate from the interaction of this histone with other components in native chromatin among which other histone H1 subfractions are good candidates. 相似文献
18.
Thierry Maillet Annie-Claude Roche Fabienne Thérain Michel Monsigny 《Cancer immunology, immunotherapy : CII》1985,19(3):177-182
Summary In vivo localization of a mouse monoclonal antibody (F2-10.23 IgM) binding leukemic L 1210 cells was studied in DBA/2 mice bearing an L 1210 tumor. F(ab)2 fragments were prepared and their specific binding to L 1210 cells was analyzed by flow cytofluorometry. Radiolocalization studies were performed by using 125I- or 131I-labeled IgM monoclonal antibody or its F(ab')2 fragments to ascertain their capacity to visualize the L 1210 tumor. F(ab)2 fragments were cleared more rapidly than the whole IgM; the clearance was as fast in healthy as in tumor-bearing mice. The tumor-to-muscle ratio observed 24 h after injection of 125I-radiolabeled F(ab)2 fragments and 125I-radiolabeled IgM was 10; the radioactivity level in the blood with F(ab)2 fragments was lower than with IgM, and so -camera imaging was workable with F(ab)2 fragments without background substraction. The tumor localization was studied over a period of 5 days by recording the distribution of the iodinated fragments in the tumor-bearing leg compared with that in the normal leg, and by computer analysis of the region of interest. F(ab)2 fragments gave better results than intact IgM in tumor visualization. Nevertheless, the rapid clearance of this antibody or its F(ab)2 fragments make them hardly suitable as carriers of toxic drugs.
Abbreviations used are: MEM Minimum essential medium; SDS sodium dodecylsulfate; PAGE polyacrylamide gel electrophoresis 相似文献
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20.
Alkane oxidation in Candida tropicalis 总被引:3,自引:0,他引:3