N‐glycosylation is one of the predominant modifications of eukaryotic proteins. It is catalyzed by oligosaccharyl transferase ( OST ), an eight‐subunit protein complex in the endoplasmic reticulum membrane. OST transfers the oligosaccharide from a lipid‐linked donor ( LLO ) to the Asn‐Xaa‐Ser/Thr sequon of nascent polypeptide, usually cotranslationally by partnering with the ribosome and the translocon. We and two other groups have recently determined high‐resolution cryo‐ EM structures of the yeast and mammalian OST complexes. In this Structural Snapshot, we describe the molecular mechanism of eukaryotic OST and its interaction with the translocon.
Reviewing the coupling coordination between urban ecological resilience (UER) and new-type urbanization (NU) has gradually become a necessary condition for understanding the structure and service patterns of urban ecological systems. Discussion on the temporal and spatial coordination evolution in UER and NU in urban agglomerations with different characteristics is beneficial for understanding the operational mechanisms of urban ecosystems. This work constructs a novel evaluation framework for the coupling coordination process between UER and NU, and scientifically measures the performance of each indicator using the entropy method and CRITIC method. By using the coupling coordination degree (CCD) model, this paper explores the spatio-temporal effects of the relationship between UER and NU, which has narrowed the cognitive gap. Using the Chengdu-Chongqing Economic Circle in China as an example, the validity and practicality of the framework are verified. The results show that the CCD between UER and NU generally shows a rapid growth trend with time and tends to be balanced; and the development patterns of CCD in urban agglomerations show significant spatial differences influenced by factors such as location advantage, natural resources, and human social activities. These results and findings can provide decision-making information reference for urban ecological system services, urban livability, and government planning.
Diabetic osteoporosis (DOP) is one of the chronic complications of diabetes mellitus, but without a standardized treatment plan till now. Liuwei Dihuang pill (LDP) has gradually exerted a remarkable effect on DOP in recent years; its specific mechanism is not clear yet.We adopted network pharmacology approaches, including multi-database search, pharmacokinetic screening, network construction analysis, gene ontology enrichment analysis, Kyoto Encyclopedia of Genes and Genomes pathway analysis and molecular docking to elaborate the active components, signaling pathways and potential mechanisms of LDP in the treatment of DOP.Twenty-seven active ingredients and 55 related disease targets have been found through integrated network pharmacology. Functional enrichment analysis shows that five key active ingredients, including beta-sitosterol, stigmasterol, diosgenin, tetrahydroalstonine, and kadsurenone, may give full scope to insulin secretion estrogen-level raising and angiogenesis in biological process through the pivotal targets. In addition, the underlying effect of PI3K/AKT/FOXO and VEGF pathways is also suggested in the treatment.Based on systematic network pharmacology methods, we predicted the basic pharmacological effects and potential mechanisms of LDP in the treatment of DOP, revealing that LDP may treat DOP through multiple targets and multiple signaling pathways, which provide evidence for the further study of pharmacological mechanism and broader clinical thinking.
Summary Genes predicted to be associated with the putative proteasome of Mycobacterium tuberculosis (Mtb) play a critical role in defence of the bacillus against nitrosative stress. However, proteasomes are uncommon in eubacteria and it remains to be established whether Mtb's prcBA genes in fact encode a proteasome. We found that coexpression of recombinant PrcB and PrcA in Escherichia coli over a prolonged period at 37°C allowed formation of an α 7 β 7 β 7 α 7 , 750 kDa cylindrical stack of four rings in which all 14 β‐subunits were proteolytically processed to expose the active site threonine. In contrast to another Actinomycete , Rhodococcus erythropolis , Mtb's β‐chain propeptide was not required for particle assembly. Peptidolytic activity of the 750 kDa particle towards a hydrophobic oligopeptide was nearly two orders of magnitude less than that of the Rhodococcus 20S proteasome, and unlike eukaryotic and archaeal proteasomes, activity of the Mtb 750 kDa particle could not be stimulated by SDS, Mg 2+ or Ca 2+ . Electron microscopy revealed what appeared to be obstructed α‐rings in the Mtb 750 kDa particle. Deletion of the N‐terminal octapeptide from Mtb's α‐chain led to disappearance of the apparent obstruction and a marked increase of peptidolytic activity. Unlike proteasomes isolated from other Actinomycetes , the open‐gate Mtb mutant 750 kDa particle cleaved oligopeptides not only after hydrophobic residues but also after basic, acidic and small, neutral amino acids. Thus, Mtb encodes a broadly active, gated proteasome that may work in concert with an endogenous activator.
Abstract A systemic theoretical study on the decomposition of 2,2-dimethoxypropane (DMP) and 2,2-diethoxypropane (DEP) in the condensed phase has been carried out. The four-center cyclic transition state is studied using the B3LYP method in DFT and the PCM and COSMORS models within the self-consistent reaction filed (SCRF) theory. The results indicate that the solvent effect and tunneling effect must be taken into account in determining the rate constant of the decomposition reaction in the condensed phase.
A tandem Hexadehydro-Diels–Alder (HDDA)/[2 + 2] cycloaddition/aryl migration reaction of iodonium ylide with tetrayne is described, in which iodonium ylide served as a unique double bond and reacted with aryne to form a four-membered iodonium(III) cycle, then converted to iodoarene after aryl group migration from iodine to adjacent carbon. This strategy allows the efficient construction of fully substituted iodoarene compounds.
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