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71.
Well Repeated Sequences
25 years of chloroplast DNA 相似文献72.
W Wyskovsky M Hohenegger B Plank G Hellmann S Klein J Suko 《European journal of biochemistry》1990,194(2):549-559
Calcium-independent calcium efflux from heavy sarcoplasmic reticulum (HSR) of skeletal muscle was found to be biphasic, with half-times of 2-6 s and 200-400 s for the first and second phase, respectively. Calcium-, AMP- and caffeine-induced calcium efflux was triphasic, with half-times of 0.05-0.2 s, 1-5 s and 100-400 s for the first, second and third phases, respectively. This very fast first phase is certainly due to calcium efflux via the calcium-release channel of HSR vesicles. Both ruthenium red and neomycin inhibited the first phase of the calcium-independent calcium efflux and the first phase of the calcium-, AMP- or caffeine-induced calcium efflux completely, whilst the second phase was fully inhibited by ruthenium red only and partially inhibited by neomycin at high concentrations, indicating that the second phase of calcium release also occurs via the calcium-release channel. Various models for calcium efflux through the release channel have been tested by simulation. Activation and inhibition of the channel-mediated calcium efflux from HSR cannot be explained by two states of the calcium-release channel (open or closed), but requires the existence of at least three states. A channel with one open state and two closed states, resulting in a rapid inactivation, is the most simple model compatible with the experimental data. According to this model, activation is assumed to reduce inactivation of the channel, whilst inhibition assumes an acceleration of channel inactivation. This mechanism most likely applies to neomycin. An additional open-blocked state has to be assumed for inhibition by ruthenium red. 相似文献
73.
Salt tolerance was found to be a species-specific character in the genus Chlorella. The most resistant species, C. luteoviridis, is able to grow in nutrient media containing up to 5% NaCl. The limit for C. protothecoides and C. saccharophila is at 4% NaCl. C. vulgaris var. vulgaris, C. fusa var. vacuolata and C. fusca var. rubescens grow in the presence of 3%, and C. fusca var. fusca, C. kessleri and C. vulgaris f. tertia in the presence of 2% NaCl. C. zofingiensis and C. minutissima are only capable of growing in media containing up to 1% NaCl, and C. homosphaera does not even tolerate 1% NaCl. Those strains, which are able to synthesize secondary carotenoids, turn orange in salt concentrations close to the limit of their tolerance. 相似文献
74.
Branchiopod crustaceans are endowed with extracellular, high-molecular-mass hemoglobins (Hbs), the functional and allosteric properties of which have largely remained obscure. The Hb of the phylogenetically ancient Triops cancriformis (Notostraca) revealed moderate oxygen affinity, cooperativity and pH dependence (Bohr effect) coefficients: P(50) = 13.3 mmHg, n(50) = 2.3, and Phi = -0.18, at 20 degrees C and pH 7.44 in Tris buffer. The in vivo hemolymph pH was 7.52. Bivalent cations increased oxygen affinity, Mg(2+) exerting a greater effect than Ca(2+). Analysis of cooperative oxygen binding in terms of the nested Monod-Wyman-Changeux (MWC) model revealed an allosteric unit of four oxygen-binding sites and functional coupling of two to three allosteric units. The predicted 2 x 4 and 3 x 4 nested structures are in accord with stoichiometric models of the quarternary structure. The allosteric control mechanism of protons comprises a left shift of the upper asymptote of extended Hill plots which is ascribable to the displacement of the equilibrium between (at least) two high-affinity (relaxed) states, similar to that found in extracellular annelid and pulmonate molluscan Hbs. Remarkably, Mg(2+) ions increased oxygen affinity solely by displacing the equilibrium between the tense and relaxed conformations towards the relaxed states, which accords with the original MWC concept, but appears to be unique among Hbs. This effect is distinctly different from those of ionic effectors (bivalent cations, protons and organic phosphates) on annelid, pulmonate and vertebrate Hbs, which involve changes in the oxygen affinity of the tense and/or relaxed conformations. 相似文献
75.
76.
Alpha-hemolysin from Staphylococcus aureus is secreted as a water-soluble monomer and assembles on membranes to oligomerize into a homo-heptameric, water-filled pore. These pores lead to lysis and cell death. Although the structure of the heptameric pore is solved by means of X-ray crystallography, structures of intermediate states-from the soluble monomer to all potential "pre-pore" structures-are yet unknown. Here, we propose a model of the monomeric alpha-hemolysin in solution based on molecular modeling, verified by small angle X-ray scattering data. This structure reveals details of the monomeric conformation of the alpha-hemolysin, for example inherent flexibility, along with definite differences in comparison to the structures used as templates. 相似文献
77.
78.
Quality control mechanisms during protein synthesis are essential to
fidelity and cell survival. Leucyl-tRNA synthetase (LeuRS) misactivates
non-leucine amino acids including isoleucine, methionine, and norvaline. To
prevent translational errors, mischarged tRNA products are translocated
30Å from the canonical aminoacylation core to a hydrolytic
editing-active site within a completely separate domain. Because it is
transient, the tRNA translocation mechanism has been difficult to isolate. We
have identified a “translocation peptide” within Escherichia
coli LeuRS. Mutations in the translocation peptide cause tRNA to
selectively bypass the editing-active site, resulting in mischarging that is
lethal to the cell. This bypass mechanism also rescues aminoacylation of an
editing site mutation that hydrolyzes correctly charged
Leu-tRNALeu. Thus, these LeuRS mutants charge tRNALeu
but fail to translocate these products to the hydrolytic site, where they are
cleared to guard against genetic code ambiguities.Quality control during translation depends on the family of aminoacyl-tRNA
synthetases (aaRSs),2
which is responsible for the first step of protein synthesis. Each aaRS
selectively aminoacylates just one of the 20 standard amino acids to its
cognate tRNA (1). About half of
this family of enzymes ensures fidelity by employing a “double sieve
model” that relies on two active sites
(2,
3). One sieve is synthetic and
produces charged tRNA. The other is a hydrolytic editing-active site that
clears mistakes. Defects in the editing mechanism cause cell death
(4,
5) and also neurological
disease in mammals (6).The aminoacylation site in the ancient canonical core of the aaRS activates
its cognate amino acid but can also misactivate structurally similar amino
acids (1). The editing-active
site blocks the correctly charged amino acid
(7,
8) and hydrolyzes mischarged
amino acids from the tRNA. Amino acid editing destroys mistakes before they
can be incorporated by the ribosome, which would result in the production of
statistical proteins (1).Amino acid proofreading requires that the charged tRNA transiently migrates
between two enzyme domains that are responsible for aminoacylation and
editing. For leucyl-tRNA synthetase (LeuRS) and the homologous
isoleucyl-(IleRS) and valyl-tRNA synthetases (ValRS), the editing domain
resides in a structural insertion called CP1
(9) that splits the Rossmann
ATP binding fold. The insert folds independent of the canonical core
(10–12).
The isolated CP1 domains from LeuRS, ValRS, and IleRS can independently and
specifically hydrolyze mischarged amino acid from its cognate tRNA
(13–15).The aminoacylation and editing-active sites of LeuRS are separated by about
30 Å. Thus, the charged 3′ end of the tRNA must be faithfully
translocated a significant distance for proofreading and then hydrolysis if it
is mischarged (16). It has
also been suggested that the tRNA 3′ end binds initially near the
editing-active site and requires translocation to the aminoacylation site
(17).We hypothesized that flexible molecular hinges might facilitate
conformational changes between the aminoacylation and the editing complexes
(18). Two putative hinge sites
were predicted by computational analysis of Thermus thermophilus
LeuRS. One hinge at Ser-227 was located in the N-terminal β-strand that
links the aminoacylation and CP1 editing domains
(18). Mutations at the
predicted hinge site in the β-strand linker of Escherichia coli
LeuRS abolished aminoacylation activity and significantly decreased amino acid
editing activity (18).A second hinge site at Glu-393 was identified in a flexible peptide within
the CP1 domain of T. thermophilus LeuRS
(18). Here, we describe
results at a homologous Asp-391 site in E. coli LeuRS that
demonstrate that this hinge comprises a portion of a translocation peptide.
Unlike the predicted β-strand hinge mutation, the aminoacylation and
editing activities of the CP1 domain-based hinge mutants in LeuRS were intact.
Surprisingly however, mutations within the translocation peptide yield
mischarged tRNA despite a robust deacylation activity. We hypothesize that
impairing the LeuRS translocation peptide causes the charged tRNA 3′ end
to bypass the editing sieve prior to product release. Defects in the
translocation peptide and its mechanism result in amino acid toxicities that
are lethal to the cell. 相似文献
79.
Victor van der Meer Henk F van Stel Moira J Bakker Albert C Roldaan Willem JJ Assendelft Peter J Sterk Klaus F Rabe Jacob K Sont 《Respiratory research》2010,11(1):74
Background
Internet-based self-management has shown to improve asthma control and asthma related quality of life, but the improvements were only marginally clinically relevant for the group as a whole. We hypothesized that self-management guided by weekly monitoring of asthma control tailors pharmacological therapy to individual needs and improves asthma control for patients with partly controlled or uncontrolled asthma.Methods
In a 1-year randomised controlled trial involving 200 adults (18-50 years) with mild to moderate persistent asthma we evaluated the adherence with weekly monitoring and effect on asthma control and pharmacological treatment of a self-management algorithm based on the Asthma Control Questionnaire (ACQ). Participants were assigned either to the Internet group (n = 101) that monitored asthma control weekly with the ACQ on the Internet and adjusted treatment using a self-management algorithm supervised by an asthma nurse specialist or to the usual care group (UC) (n = 99). We analysed 3 subgroups: patients with well controlled (ACQ ≤ 0.75), partly controlled (0.75>ACQ ≤ 1.5) or uncontrolled (ACQ>1.5) asthma at baseline.Results
Overall monitoring adherence was 67% (95% CI, 60% to 74%). Improvements in ACQ score after 12 months were -0.14 (p = 0.23), -0.52 (p < 0.001) and -0.82 (p < 0.001) in the Internet group compared to usual care for patients with well, partly and uncontrolled asthma at baseline, respectively. Daily inhaled corticosteroid dose significantly increased in the Internet group compared to usual care in the first 3 months in patients with uncontrolled asthma (+278 μg, p = 0.001), but not in patients with well or partly controlled asthma. After one year there were no differences in daily inhaled corticosteroid use or long-acting β2-agonists between the Internet group and usual care.Conclusions
Weekly self-monitoring and subsequent treatment adjustment leads to improved asthma control in patients with partly and uncontrolled asthma at baseline and tailors asthma medication to individual patients'' needs.Trial registration
Current Controlled Trials ISRCTN79864465 相似文献80.