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排序方式: 共有690条查询结果,搜索用时 15 毫秒
621.
Idicula-Thomas S Kulkarni AJ Kulkarni BD Jayaraman VK Balaji PV 《Bioinformatics (Oxford, England)》2006,22(3):278-284
MOTIVATION: Inclusion body formation has been a major deterrent for overexpression studies since a large number of proteins form insoluble inclusion bodies when overexpressed in Escherichia coli. The formation of inclusion bodies is known to be an outcome of improper protein folding; thus the composition and arrangement of amino acids in the proteins would be a major influencing factor in deciding its aggregation propensity. There is a significant need for a prediction algorithm that would enable the rational identification of both mutants and also the ideal protein candidates for mutations that would confer higher solubility-on-overexpression instead of the presently used trial-and-error procedures. RESULTS: Six physicochemical properties together with residue and dipeptide-compositions have been used to develop a support vector machine-based classifier to predict the overexpression status in E.coli. The prediction accuracy is approximately 72% suggesting that it performs reasonably well in predicting the propensity of a protein to be soluble or to form inclusion bodies. The algorithm could also correctly predict the change in solubility for most of the point mutations reported in literature. This algorithm can be a useful tool in screening protein libraries to identify soluble variants of proteins. 相似文献
622.
High-density lipoproteins (HDL) mediate cholesterol removal and thereby protect against atherosclerosis. Mature spherical HDL contain the apolar lipid core and polar surface of proteins and phospholipids. Earlier, we showed that the structural integrity of HDL is modulated by kinetic barriers that prevent spontaneous protein dissociation and lipoprotein fusion and rupture. To determine the role of electrostatic interactions in the kinetic stability of mature HDL, here we analyze the effects of salt and pH on their thermal denaturation. In low-salt buffer at pH 5.7-7.7, HDL are highly thermostable. Increasing the salt concentration from 0 to 0.3 M NaCl causes low-temperature shifts in the calorimetric HDL transitions of up to -14 degrees C. This salt-induced destabilization leads to protein unfolding below 100 degrees C, facilitating the first Arrhenius analysis of HDL denaturation by circular dichroism spectroscopy. In 150 mM NaCl, two kinetic phases in HDL protein unfolding are observed: a faster phase with an activation energy E(a,fast) < or =15 kcal/mol and a slower phase with an E(a,slow) = 50 +/- 7 kcal/mol. Gel electrophoresis and electron microscopic data suggest that the faster phase involves partial protein unfolding but no significant protein dissociation or changes in HDL size, while the slower phase involves complete protein unfolding, partial protein dissociation, and HDL fusion. Hence, the slower phase may resemble HDL remodeling and fusion by plasma enzymes during metabolism. Analysis of the effects of various salts, sucrose, and pH suggests that HDL destabilization by salt results from ionic screening of favorable short-range electrostatic interactions such as salt bridges. Consequently, electrostatic interactions significantly contribute to the high thermostability of HDL in low-salt solutions. 相似文献
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Elad Noor Avi I. Flamholz Vijay Jayaraman Brian L. Ross Yair Cohen Wayne M. Patrick Ita GruicSovulj Dan S. Tawfik 《Protein science : a publication of the Protein Society》2022,31(8)
Enzymes are well known for their catalytic abilities, some even reaching “catalytic perfection” in the sense that the reaction they catalyze has reached the physical bound of the diffusion rate. However, our growing understanding of enzyme superfamilies has revealed that only some share a catalytic chemistry while others share a substrate‐handle binding motif, for example, for a particular phosphate group. This suggests that some families emerged through a “substrate‐handle‐binding‐first” mechanism (“binding‐first” for brevity) instead of “chemistry‐first” and we are, therefore, left to wonder what the role of non‐catalytic binders might have been during enzyme evolution. In the last of their eight seminal, back‐to‐back articles from 1976, John Albery and Jeremy Knowles addressed the question of enzyme evolution by arguing that the simplest mode of enzyme evolution is what they defined as “uniform binding” (parallel stabilization of all enzyme‐bound states to the same degree). Indeed, we show that a uniform‐binding proto‐catalyst can accelerate a reaction, but only when catalysis is already present, that is, when the transition state is already stabilized to some degree. Thus, we sought an alternative explanation for the cases where substrate‐handle‐binding preceded any involvement of a catalyst. We find that evolutionary starting points that exhibit negative catalysis can redirect the reaction''s course to a preferred product without need for rate acceleration or product release; that is, if they do not stabilize, or even destabilize, the transition state corresponding to an undesired product. Such a mechanism might explain the emergence of “binding‐first” enzyme families like the aldolase superfamily. 相似文献
626.
The distribution pattern of alpha-melanocyte stimulating hormone-like immunoreactivity (alpha-MSH-Li) was studied in cats using avidin-biotin modification of immunocytochemical method. Cell bodies containing alpha-MSH-Li were observed in the medial basal hypothalamus, especially in the infundibular nucleus, the lateral hypothalamus and near zona incerta. Fibers with alpha-MSH-Li extended beyond the hypothalamus, into the paraventricular nucleus of the thalamus, rostral amygdala, periaqueductal gray, locus ceruleus, parabrachial nucleus and medial nucleus of the nucleus tractus solitarius. Axons with alpha-MSH-Li were also seen diffusely in various cortical areas, but more extensively in the limbic cortical regions. The distribution pattern of the cell bodies and fibers containing alpha-MSH-Li bears several similarities to that seen in rats, but differs in that the alpha-MSH-Li was not observed in cell bodies in locations other than the medial basal and lateral hypothalamus. 相似文献
627.
Electron density profile of two-dimensionally crystalline membranous cytochrome c oxidase at low resolution. 下载免费PDF全文
Unilamellar vesicles of membranous cytochrome c oxidase have been isolated whose distribution of protein in the membrane plane was predominantly crystalline. The vesicles were collapsed via controlled partial dehydration, resulting, at first, in the formation of unoriented, mostly unstacked, membrane pairs. Further controlled partial dehydration resulted in the formation of oriented multilayers of stacks of membrane pairs, retaining the in-plane crystallinity. The above were monitored by electron microscopy and x-ray diffraction. Analysis of the x-ray diffraction from unoriented, unstacked membrane pairs by two independent methods provided the membrane electron density profile to 30 A resolution. 相似文献
628.
Earlier studies in the phenyltrimethylamino (TMA) hapten system demonstrated that under certain conditions idiotype-specific second-order T suppressor (Ts2)-bearing mice fail to suppress TMA-specific delayed-type hypersensitivity. This was due to a functional deletion in the third-order T suppressor (Ts3) subset. In this report we have confirmed and extended these findings to show that only homologous TMA-specific Ts3 can restore suppressor function, both heterologous Ts3 and unprimed T-cell populations failed to do so. Furthermore, attempts to induce Ts3 function in the defective mice after reconstitution with normal precursor Ts3 cells also failed. In contrast, protocols which induce heterologous contact and cutaneous hypersensitivity reactions readily induced cell populations capable of restoring suppression in the Ts3-defective mice. Analysis of the lymphoid populations from the contact-sensitized defective mice revealed that these cells were not the prototypical Ts3 but were similar to the previously reported nonspecific T acceptor cell. The results further indicated that the T acceptor cell functioned as the active terminal-phase Ts subset, and this could be used as an alternative to the TMA-specific Ts3. The importance of multiple suppressor pathways at the terminal phase of immune suppression is discussed. 相似文献
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