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81.
Royston Goodacre Eadaoin M. Timmins Paul J. Rooney Jem J. Rowland Douglas B. Kell 《FEMS microbiology letters》1996,140(2-3):233-239
82.
Pooja Malhotra Jayant B. Udgaonkar 《Protein science : a publication of the Protein Society》2016,25(11):1924-1941
A thermodynamically and kinetically simple picture of protein folding envisages only two states, native (N) and unfolded (U), separated by a single activation free energy barrier, and interconverting by cooperative two‐state transitions. The folding/unfolding transitions of many proteins occur, however, in multiple discrete steps associated with the formation of intermediates, which is indicative of reduced cooperativity. Furthermore, much advancement in experimental and computational approaches has demonstrated entirely non‐cooperative (gradual) transitions via a continuum of states and a multitude of small energetic barriers between the N and U states of some proteins. These findings have been instrumental towards providing a structural rationale for cooperative versus noncooperative transitions, based on the coupling between interaction networks in proteins. The cooperativity inherent in a folding/unfolding reaction appears to be context dependent, and can be tuned via experimental conditions which change the stabilities of N and U. The evolution of cooperativity in protein folding transitions is linked closely to the evolution of function as well as the aggregation propensity of the protein. A large activation energy barrier in a fully cooperative transition can provide the kinetic control required to prevent the accumulation of partially unfolded forms, which may promote aggregation. Nevertheless, increasing evidence for barrier‐less “downhill” folding, as well as for continuous “uphill” unfolding transitions, indicate that gradual non‐cooperative processes may be ubiquitous features on the free energy landscape of protein folding. 相似文献
83.
Donata Rimoldi Kim E. Creek Luigi M. De Luca 《Molecular and cellular biochemistry》1990,93(2):129-140
Summary The molecular mechanism of reduced incorporation of radioactively labeled mannose into hamster liver glycoconjugates during the progression of vitamin A deficiency was investigated. In particular the in vivo incorporation of [2-3H]mannose into GDP-mannose, dolichyl phosphate mannose (Dol-P-Man), lipid-linked oligosaccharides, and glycopeptides of hamster liver was examined. Hamsters maintained on a vitamin A-free diet showed a reduction in the incorporation of mannose into GDP-mannose about 10 days before clinical signs of vitamin A deficiency could be observed. The decrease in [2-3H]mannose incorporated into GDP-mannose was accompanied by a reduction in label incorporated into Dol-P-Man, lipid linked oligosaccharides and glycopeptides, which became more severe with the progression of vitamin A deficiency. By the time they reached a plateau stage of growth, hamsters fed the vitamin A-free diet showed a 50% reduction in the amount of [2-3H]mannose converted to GDP-mannose, and the radioactivity associated with Dol-P-Man and glycopeptides was reduced by approximately 60% as compared to retinoic acid-supplemented controls. These results strongly indicate that the reduced incorporation of mannose into lipidic intermediates and glycoproteins observed during vitamin A deficiency is due to impaired GDP-mannose synthesis.Abbreviations Dol-P-Man
Dolichyl Phosphate Mannose
- Dol-P
Dolichyl Phosphate 相似文献
84.
The epimastigote or culture form of Trypanosoma cruzi oxidizes [3-14C] pyruvate and [2-14C] acetate to 14CO2 without an apparent increase in overall respiration. This oxidation takes place through the tricarboxylic acid cycle as shown by (a) the incorporation of substrate 14C into cycle intermediates; (b) the earlier liberation of acetate carboxyl carbon as CO2; and (c) the characteristic intramolecular distribution of pyruvate and acetate carbon atoms in the skeletal carbon of aspartic and glutamic acids. Upon oxidation of [3-14C] pyruvate and [2-14C] acetate, two of the products, alanine and glutamic acid, are found to account for more than 50% of incorporated 14C; labeling of alanine predominates with [3-14C] pyruvate while labeling of glutamic acid predominates with [2-14C] acetate. Using [1- or 6-14C] glucose as substrate, the pattern of 14C distribution in soluble metabolites closely resembles that obtained with [3-14C] pyruvate, in accordance with the joint operation of the Embden-Meyerhof pathway and Krebs cycle. The cycle operation depends on electron transport through the mitochondrial respiratory chain, since antimycin A, at a relatively low concentration, inhibits the oxidation of [2-14C] acetate to 14CO2, to the same extent as the parasite respiration. Though functional in T. cruzi epimastigotes, the oxidative role of the Krebs’ cycle is apparently limited by the absence of an efficient oxidative apparatus. The cycle operation does, however, constitute an important source of skeletal carbon for the biosynthesis of amino acids and can contribute to the process of glycogenesis. 相似文献
85.
Abstract Ultrastructural and physiological characteristics of the C3-C4 intermediate Neurachne minor S. T. Blake (Poaceae) are compared with those of C3 and C4 relatives, and C3-C4Panicum milioides Nees ex Trin. N. minor consistently exhibits very low CO2 compensation points (τ: 1.0, usually 0.3–0.6 Pa) yet has C3-like δ13C values. CO2 assimilation rates (A) respond like those of C3 plants to a decrease in O2 partial pressure (2 × 104–1.9 × 103 Pa) at ambient CO2 levels, but this response is progressively attenuated until negligible at very low CO2. By contrast, other species of the Neurachneae are clearly either C4 (two spp.) or C3 (seven spp.). For plants grown and measured at different photon flux densities (PFDs), τ for N. minor and P. milioides increases from 0.5 to 1.0, and from 1.0 to 2.1 Pa, respectively, as PFD is decreased from 1860 to 460 μmol m?2s?1. In N. minor, the O2 response of τ is either biphasic as in P. milioides, but much diminished and with a higher transition point, or is very C4-like. As in C4 relatives, inner sheath cells contain numerous chloroplasts. Their walls possess a suberized lamella, which may make them more CO2-tight than bundle sheath cells of P. milioides, contributing to the almost C4-like τ characteristics of N. minor. The biochemical basis of C3-C4 intermediacy is considered. 相似文献
86.
Changes in the level of alkaline inorganic pyrophosphatase and ADPG-pyrophosphorylase were monitored in developing wheat grains at weekly intervals aft 相似文献
87.
The intermediates of trans-bacteriorhodopsin (trans-bR) in the photoreaction cycle were investigated under two different conditions. In a low salt and neutral pH medium (10 mM phosphate buffer, pH 6.6), trans-bR was irradiated with 500 nm light at –190 C, resulting in formation of batho-trans-bR (batho-bRt). On warming in the dark, batho-bRt converted to lumi-trans-bR (lumi-bRt), meta-trans-bR (meta-bRt) and finally to trans-bR. The intermediates N and O, which had been detected by others by flash photolysis, were not observed. The thermal decay of lumi-bRt in a high salt and high pH medium (10 mM borate buffer with l M NaCl, pH 10.0) proceeded simultaneously through two pathways; one to meta-bRt and another to trans-bR. About 72% of lumi-bRt converted to trans-bR directly and the residue converted to meta-bRt. By use of this value, the absorption spectra of batho-bRt (max: 626 nm), lumi-bRt (max: 543 nm) and meta-bRt (max: 418 nm) were calculated. A photoreaction cycle of bacteriorhodopsin was proposed on the basis of the above findings. 相似文献
88.
89.
When a protein folds or unfolds, it passes through many half-folded microstates. Only a few of them can accumulate and be seen experimentally, and this happens only when the folding (or unfolding) occurs far from the point of thermodynamic equilibrium between the native and denatured states. The universal features of folding, though, are observed in the vicinity of the equilibrium point. Here the two-state transition proceeds without any accumulation of metastable intermediates, and only the transition state (folding nucleus) is outlined by its key influence on the folding/unfolding kinetics. This review covers recent experimental and theoretical studies of folding nuclei. 相似文献
90.
J. Rui Rodrigues Carlos J. V. Simões Cândida G. Silva Rui M. M. Brito 《Protein science : a publication of the Protein Society》2010,19(2):202-219
Protein aggregation into insoluble fibrillar structures known as amyloid characterizes several neurodegenerative diseases, including Alzheimer's, Huntington's and Creutzfeldt‐Jakob. Transthyretin (TTR), a homotetrameric plasma protein, is known to be the causative agent of amyloid pathologies such as FAP (familial amyloid polyneuropathy), FAC (familial amyloid cardiomiopathy) and SSA (senile systemic amyloidosis). It is generally accepted that TTR tetramer dissociation and monomer partial unfolding precedes amyloid fibril formation. To explore the TTR unfolding landscape and to identify potential intermediate conformations with high tendency for amyloid formation, we have performed molecular dynamics unfolding simulations of WT‐TTR and L55P‐TTR, a highly amyloidogenic TTR variant. Our simulations in explicit water allow the identification of events that clearly discriminate the unfolding behavior of WT and L55P‐TTR. Analysis of the simulation trajectories show that (i) the L55P monomers unfold earlier and to a larger extent than the WT; (ii) the single α‐helix in the TTR monomer completely unfolds in most of the L55P simulations while remain folded in WT simulations; (iii) L55P forms, early in the simulations, aggregation‐prone conformations characterized by full displacement of strands C and D from the main β‐sandwich core of the monomer; (iv) L55P shows, late in the simulations, severe loss of the H‐bond network and consequent destabilization of the CBEF β‐sheet of the β‐sandwich; (v) WT forms aggregation‐compatible conformations only late in the simulations and upon extensive unfolding of the monomer. These results clearly show that, in comparison with WT, L55P‐TTR does present a much higher probability of forming transient conformations compatible with aggregation and amyloid formation. 相似文献