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1.
Hong-Hsiang Guan Yen-Hua Huang En-Shyh Lin Chun-Jung Chen Cheng-Yang Huang 《Molecules (Basel, Switzerland)》2021,26(23)
Dihydroorotase (DHOase), a dimetalloenzyme containing a carbamylated lysine within the active site, is a member of the cyclic amidohydrolase family, which also includes allantoinase (ALLase), dihydropyrimidinase (DHPase), hydantoinase, and imidase. Unlike most known cyclic amidohydrolases, which are tetrameric, DHOase exists as a monomer or dimer. Here, we report and analyze two crystal structures of the eukaryotic Saccharomyces cerevisiae DHOase (ScDHOase) complexed with malate. The structures of different DHOases were also compared. An asymmetric unit of these crystals contained four crystallographically independent ScDHOase monomers. ScDHOase shares structural similarity with Escherichia coli DHOase (EcDHOase). Unlike EcDHOase, ScDHOase can form tetramers, both in the crystalline state and in solution. In addition, the subunit-interacting residues of ScDHOase for dimerization and tetramerization are significantly different from those of other DHOases. The tetramerization pattern of ScDHOase is also different from those of DHPase and ALLase. Based on sequence analysis and structural evidence, we identify two unique helices (α6 and α10) and a loop (loop 7) for tetramerization, and discuss why the residues for tetramerization in ScDHOase are not necessarily conserved among DHOases. 相似文献
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Lycopene is a well-known compound found commonly in tomatoes which brings wide range of health benefits against cardiovascular diseases and cancers. From an anti-cancer perspective, lycopene is often associated with reduced risk of prostate cancer and people often look for it as a dietary supplement which may help to prevent cancer. Previous scientific evidence exhibited that the anti-cancer activity of lycopene relies on its ability to suppress oncogene expressions and induce proapoptotic pathways. To further explore the real potential of lycopene in cancer prevention, this review discusses the new insights and perspectives on the anti-cancer activities of lycopene which could help to drive new direction for research. The relationship between inflammation and cancer is being highlighted, whereby lycopene suppresses cancer via resolution of inflammation are also discussed herein. The immune system was found to be a part of the anti-cancer system of lycopene as it modulates immune cells to suppress tumor growth and progression. Lycopene, which is under the family of carotenoids, was found to play special role in suppressing lung cancer. 相似文献
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Xinheng He Ning Huang Yuran Qiu Jian Zhang Yaqin Liu Xiao-Lan Yin Shaoyong Lu 《Molecules (Basel, Switzerland)》2021,26(4)
Metastasis is the major cause of death in colorectal cancer and it has been proven that inhibiting an interaction between adenomatous polyposis coli (APC) and Rho guanine nucleotide exchange factor 4 (Asef) efficaciously restrain metastasis. However, current inhibitors cannot achieve a satisfying effect in vivo and need to be optimized. In the present study, we applied molecular dynamics (MD) simulations and extensive analyses to apo and holo APC systems in order to reveal the inhibitor mechanism in detail and provide insights into optimization. MD simulations suggested that apo APC takes on a broad array of conformations and inhibitors stabilize conformation selectively. Representative structures in trajectories show specific APC-ligand interactions, explaining the different binding process. The stability and dynamic properties of systems elucidate the inherent factors of the conformation selection mechanism. Binding free energy analysis quantitatively confirms key interface residues and guide optimization. This study elucidates the conformation selection mechanism in APC-Asef inhibition and provides insights into peptide-based drug design. 相似文献
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Xuanfeng Yue Siavash Vahidi Lars Konermann 《Journal of the American Society for Mass Spectrometry》2014,25(8):1322-1331
The mechanisms whereby protein ions are liberated from charged droplets during electrospray ionization (ESI) remain under investigation. Compact conformers electrosprayed from aqueous solution in positive ion mode likely follow the charged residue model (CRM), which envisions analyte release after solvent evaporation to dryness. The concentration of nonvolatile salts such as NaCl increases sharply within vanishing CRM droplets, promoting nonspecific pairing of Cl- and Na+ with charged groups on the protein surface. For unfolded proteins, it has been proposed that ion formation occurs via the chain ejection model (CEM). During the CEM proteins are expelled from the droplet long before complete solvent evaporation has taken place. Here we examine whether salt adduction levels support the view that folded and unfolded proteins follow different ESI mechanisms. Solvent evaporation during the CEM is expected to be less extensive and, hence, the salt concentration at the point of protein release should be substantially lower than for the CRM. CEM ions should therefore exhibit lower adduction levels than CRM species. We explore the adduction behavior of several proteins that were chosen to allow comparative studies on folded and unfolded structures in the same solution. In-source activation eliminates chloride adducts via HCl release, generating protein ions that are heterogeneously charged because of sodiation and protonation. Sodiation levels measured under such conditions provide estimates of the salt adduction behavior experienced by the “nascent” analyte ions. Sodiation levels are significantly reduced for unfolded proteins, supporting the view that these species are indeed formed via the CEM. Figure
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We present the first-principle calculations on the electronic excitations and second-order properties in solution phase of
two typical inorganic trinuclear anionic clusters, [MoCu2S4(SPh)2]2− and [Mo2CuS4]1−(edt)2(PPh3) (edt=1,2-ethanedithiolato) in the framework of density functional theory (DFT). The computed excitation energies are in good agreement
with the outcome of the measurements. The predicted values of the molecular quadratic hyperpolarizabilities are of the comparable
order of those of the typical organometallic chromophores. We demonstrate the significant contributions to the second-order
responses from the charge transfers between the metal centers (MMCT) which are ascribed to the direct metal–metal bonding interactions in these two charged clusters. This meaningful ligand-independent mechanism for the second-order response largely relates to metal–metal bonding strength, and the understanding will benefit
to the future design of the new-generation molecular based nonlinear optical materials and optoelectronic devices by means
of the conscious tuning of metal–metal interactions and metal-core structures of inorganic polynuclear clusters. 相似文献
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Ignacio Medina-Mercado Dr. Susana Porcel 《Chemistry (Weinheim an der Bergstrasse, Germany)》2020,26(69):16206-16221
In the last decade, aryldiazonium salts have attracted interest as coupling partners in cross-coupling reactions mediated by gold. Initially, the presence of a photocatalyst and a light source was needed to achieve gold oxidation with these electrophiles. However, recently, it has been shown that in some instances just heating, light irradiation, or the addition of certain bases and/or nucleophiles is enough. In this review, the transformations developed so far using aryldiazonium salts as electrophiles are summarized with special emphasis on mechanistic studies. The information gained by different authors, indicates that the specific steps of gold oxidation with aryldiazonium salts depends upon the activation mode of the diazonium salt. 相似文献
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Shujiang Wang Deepanjali Gurav Dr. Oommen P. Oommen Prof. Oommen P. Varghese 《Chemistry (Weinheim an der Bergstrasse, Germany)》2015,21(15):5980-5985
The dynamic covalent‐coupling reaction involving α‐effect nucleophiles has revolutionized bioconjugation approaches, due to its ease and high efficiency. Key to its success is the discovery of aniline as a nucleophilic catalyst, which made this reaction feasible under physiological conditions. Aniline however, is not so effective for keto substrates. Here, we investigate the mechanism of aniline activation in the oxime reaction with aldehyde and keto substrates. We also present carboxylates as activating agents that can promote the oxime reaction with both aldehyde and keto substrates at physiological pH. This rate enhancement circumvents the influence of α‐effect by forming H‐bonds with the rate‐limiting intermediate, which drives the reaction to completion. The combination of aniline and carboxylates had a synergistic effect, resulting in a ~14–31‐fold increase in reaction rate at pD 7.4 with keto substrates. The biocompatibility and efficiency of carboxylate as an activating agent is demonstrated by performing cell‐surface oxime labeling at physiological pH using acetate, which showed promising results that were comparable with aniline. 相似文献
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Dr. Albert A. Smith Emelyne M. Pacull Sabrina Stecher Prof. Dr. Peter W. Hildebrand Dr. Alexander Vogel Prof. Dr. Daniel Huster 《Angewandte Chemie (International ed. in English)》2023,62(35):e202383561
G protein-coupled receptors initiate signal transduction in response to ligand binding. Growth hormone secretagogue receptor (GHSR), the focus of this study, binds the 28 residue peptide ghrelin. While structures of GHSR in different states of activation are available, dynamics within each state have not been investigated in depth. We analyze long molecular dynamics simulation trajectories using “detectors” to compare dynamics of the apo and ghrelin-bound states yielding timescale-specific amplitudes of motion. We identify differences in dynamics between apo and ghrelin-bound GHSR in the extracellular loop 2 and transmembrane helices 5–7. NMR of the GHSR histidine residues reveals chemical shift differences in these regions. We evaluate timescale specific correlation of motions between residues of ghrelin and GHSR, where binding yields a high degree of correlation for the first 8 ghrelin residues, but less correlation for the helical end. Finally, we investigate the traverse of GHSR over a rugged energy landscape via principal component analysis. 相似文献
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ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF. 相似文献
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Tom D. Heightman Andrea T. Vasella 《Angewandte Chemie (International ed. in English)》1999,38(6):750-770
Not “from above”, but “from the side” : Configuration-retaining β-glycosidases protonate their substrate either anti or syn to the endocyclic C1−O bond as the first step in the enzymic cleavage of the glycosidic bond (see schematic drawing). Insights into the mechanism of action of glycosidases have been gained by a combination of the synthesis of inhibitors, the study of the kinetics of their inhibition, and the analysis of the crystal structures of glycosidases and glycosidase–ligand complexes. 相似文献
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Kristof Van der Borght Rakesh Batchu Dr. Vladimir V. Galvita Dr. Konstantinos Alexopoulos Prof. Marie‐Françoise Reyniers Prof. Joris W. Thybaut Prof. Guy B. Marin 《Angewandte Chemie (International ed. in English)》2016,55(41):12817-12821
Ethanol dehydration to ethene is mechanistically decoupled from the production of higher hydrocarbons due to complete surface coverage by adsorbed ethanol and diethyl ether (DEE). The production of C3+ hydrocarbons was found to be unaffected by water present in the reaction mixture. Three routes for the production of C3+ hydrocarbons are identified: the dimerization of ethene to butene and two routes involving two different types of surface species categorized as aliphatic and aromatic. Evidence for the different types of species involved in the production of higher hydrocarbons is obtained via isotopic labeling, continuous flow and transient experiments complemented by UV/Vis characterization of the catalyst and ab initio microkinetic modeling. 相似文献
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Dr. Yuriy Rebets Dr. Elke Brötz Niko Manderscheid Dr. Bogdan Tokovenko Dr. Maksym Myronovskyi Prof. Dr. Peter Metz Dr. Lutz Petzke Dr. Andriy Luzhetskyy 《Angewandte Chemie (International ed. in English)》2015,54(7):2280-2284
Pamamycins are macrodiolides of polyketide origin with antibacterial activities. Their biosynthesis has been proposed to utilize succinate as a building block. However, the mechanism of succinate incorporation into a polyketide was unclear. Here, we report identification of a pamamycin biosynthesis gene cluster by aligning genomes of two pamamycin‐producing strains. This unique cluster contains polyketide synthase (PKS) genes encoding seven discrete ketosynthase (KS) enzymes and one acyl‐carrier protein (ACP)‐encoding gene. A cosmid containing the entire set of genes required for pamamycin biosynthesis was successfully expressed in a heterologous host. Genetic and biochemical studies allowed complete delineation of pamamycin biosynthesis. The pathway proceeds through 3‐oxoadipyl‐CoA, a key intermediate in the primary metabolism of the degradation of aromatic compounds. 3‐Oxoadipyl‐CoA could be used as an extender unit in polyketide assembly to facilitate the incorporation of succinate. 相似文献
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The mechanism of the reduction of phosphine oxides by PhSiH3 was established on the basis of kinetic measurements and Density Functional Theory (DFT) calculations. In particular, it has been proved that the model reaction between tri‐n‐butylphosphine oxide and phenylsilane occurs via a nonpolar mechanism. The data presented herein allow prediction and verification of the applicability of the new reduction reagents and conditions for industrially attractive processes. 相似文献
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Chemical Synthesis of Phosphorylated Histone H2A at Tyr57 Reveals Insight into the Inhibition Mode of the SAGA Deubiquitinating Module
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Muhammad Jbara Dr. Suman Kumar Maity Dr. Michael Morgan Prof. Cynthia Wolberger Prof. Ashraf Brik 《Angewandte Chemie (International ed. in English)》2016,55(16):4972-4976
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Max S. Coles Gina Quach Dr. Jonathon E. Beves Dr. Evan G. Moore 《Angewandte Chemie (Weinheim an der Bergstrasse, Germany)》2020,132(24):9609-9613
The development of photocatalytic reactions has provided many novel opportunities to expand the scope of synthetic organic chemistry. In parallel with progress towards uncovering new reactivity, there is consensus that efforts focused on providing detailed mechanistic insight in order to uncover underlying excited-state reactions are essential to maximise formation of desired products. With this in mind, we have investigated the recently reported sensitization-initiated electron transfer (SenI-ET) reaction for the C−H arylation of activated aryl halides. Using a variety of techniques, and in particular nanosecond transient absorption spectroscopy, we are able to distinguish several characteristic signals from the excited-state species involved in the reaction, and subsequent kinetic analysis under various conditions has facilitated a detailed insight into the likely reaction mechanism. 相似文献
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<正>During the past decade, organic-inorganic hybrid perovskite solar cell(PSC) has attracted great attention in the photovoltaic field 1,2. As the third-generation solar cell, PSC in laboratory has already achieved certified power conversion efficiency(PCE) exceeding 25%. 相似文献
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Jiaman Liu Yuqing Liu Xiaofeng He Bo Teng Jacqui M. McRae 《Molecules (Basel, Switzerland)》2021,26(9)
Valonea tannin is a natural product readily extracted from acorn shells that has been suggested to have potential skin whitening properties. This study investigated the tyrosinase inhibition activity of extracted valonea tannin and the associated structure–function activity. Nuclear magnetic resonance spectroscopy and molecular weight analysis with gel permeation chromatography revealed that valonea tannin could be characterized as a hydrolysable tannin with galloyl, hexahydroxydiphenoyl and open formed-glucose moieties and an average molecular weight of 3042 ± 15 Da. Tyrosinase inhibition assays demonstrated that valonea tannin was 334 times more effective than gallic acid and 3.4 times more effective than tannic acid, which may relate to the larger molecular size. Kinetic studies of the inhibition reactions indicated that valonea tannin provided tyrosinase inhibition through mixed competitive–uncompetitive way. Stern–Volmer fitted fluorescence quenching analysis, isothermal titration calorimetry analysis and in silico molecule docking showed valonea tannin non-selectively bound to the surface of tyrosinase via hydrogen bonds and hydrophobic interactions. Inductively coupled plasma-optical emission spectroscopy and free radical scavenging assays indicated the valonea tannin had copper ion chelating and antioxidant ability, which may also contribute to inhibition activity. These results demonstrated the structure–function activity of valonea tannin as a highly effective natural tyrosinase inhibitor that may have commercial application in dermatological medicines or cosmetic products. 相似文献