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71.
Zygmunt Kazimierczuk Ryszard Stolarski Lech Dudycz David Shugar 《Nucleosides, nucleotides & nucleic acids》2013,32(3):275-287
Abstract The 1-β-D-ribofuranosides of several 2-trifluoromethyl benzimidazoles were prepared by the fusion method, and their conformations, particularly about the glycosidic bond, determined by 1H NMR spectroscopy. 相似文献
72.
Abstract A procedure was developed for the chemical synthesis of P1,P2-dinucleoside-5′-diphosphates (N1(5′)pp(5′)N2) on a nanomolar scale Reaction conditions for activating purine-5′-monophosphates (pA, pG, and pm7G) by 1,1′-carbonyldiimidazole were studied and optimized in respect to solvents and amount of activating reagent used. Various dinucleoside-5′-diphosphates were synthesized in 62-98% yield by incubating activated and non-activated purine-5′-monophosphates. Two unexpected by-products were formed by competition reactions: the imidazolidate of the non-activated nucleotide and the corresponding symmetrically substituted dinucleoside-5′-diphosphate. A mechanism is proposed to explain the observed side reactions. 相似文献
73.
Alvaro J. Amor Karl R. Schmitz Tania A. Baker Robert T. Sauer 《Protein science : a publication of the Protein Society》2019,28(4):756-765
IGF‐motif loops project from the hexameric ring of ClpX and are required for docking with the self‐compartmentalized ClpP peptidase, which consists of heptameric rings stacked back‐to‐back. Here, we show that ATP or ATPγS support assembly by changing the conformation of the ClpX ring, bringing the IGF loops closer to each other and allowing efficient multivalent contacts with docking clefts on ClpP. In single‐chain ClpX pseudohexamers, deletion of one or two IGF loops modestly slows association with ClpP but strongly accelerates dissociation of ClpXP complexes. We probe how changes in the sequence and length of the IGF loops affect ClpX–ClpP interactions and show that deletion of one or two IGF loops slows ATP‐dependent proteolysis by ClpXP. We also find that ClpXP degradation is less processive when two IGF loops are deleted. 相似文献
74.
Alessandro Esposito Valeria Ventura Maxim V. Petoukhov Amrita Rai Dmitri I. Svergun Maria A. Vanoni 《Protein science : a publication of the Protein Society》2019,28(1):150-166
Human MICAL1 is a member of a recently discovered family of multidomain proteins that couple a FAD‐containing monooxygenase‐like domain to typical protein interaction domains. Growing evidence implicates the NADPH oxidase reaction catalyzed by the flavoprotein domain in generation of hydrogen peroxide as a second messenger in an increasing number of cell types and as a specific modulator of actin filaments stability. Several proteins of the Rab families of small GTPases are emerging as regulators of MICAL activity by binding to its C‐terminal helical domain presumably shifting the equilibrium from the free – auto‐inhibited – conformation to the active one. We here extend the characterization of the MICAL1–Rab8 interaction and show that indeed Rab8, in the active GTP‐bound state, stabilizes the active MICAL1 conformation causing a specific four‐fold increase of kcat of the NADPH oxidase reaction. Kinetic data and small‐angle X‐ray scattering (SAXS) measurements support the formation of a 1:1 complex between full‐length MICAL1 and Rab8 with an apparent dissociation constant of approximately 8 μM. This finding supports the hypothesis that Rab8 is a physiological regulator of MICAL1 activity and shows how the protein region preceding the C‐terminal Rab‐binding domain may mask one of the Rab‐binding sites detected with the isolated C‐terminal fragment. SAXS‐based modeling allowed us to propose the first model of the free full‐length MICAL1, which is consistent with an auto‐inhibited conformation in which the C‐terminal region prevents catalysis by interfering with the conformational changes that are predicted to occur during the catalytic cycle. 相似文献
75.
Joaquín Dalla Rizza Lía M. Randall Javier Santos Gerardo Ferrer‐Sueta Ana Denicola 《Protein science : a publication of the Protein Society》2019,28(1):191-201
Peroxiredoxins are thiol‐dependent peroxidases that function in peroxide detoxification and H2O2 induced signaling. Among the six isoforms expressed in humans, PRDX1 and PRDX2 share 97% sequence similarity, 77% sequence identity including the active site, subcellular localization (cytosolic) but they hold different biological functions albeit associated with their peroxidase activity. Using recombinant human PRDX1 and PRDX2, the kinetics of oxidation and hyperoxidation with H2O2 and peroxynitrite were followed by intrinsic fluorescence. At pH 7.4, the peroxidatic cysteine of both isoforms reacts nearly tenfold faster with H2O2 than with peroxynitrite, and both reactions are orders of magnitude faster than with most protein thiols. For both isoforms, the sulfenic acids formed are in turn oxidized by H2O2 with rate constants of ca 2 × 103 M?1 s?1 and by peroxynitrous acid significantly faster. As previously observed, a crucial difference between PRDX1 and PRDX2 is on the resolution step of the catalytic cycle, the rate of disulfide formation (11 s?1 for PRDX1, 0.2 s?1 for PRDX2, independent of the oxidant) which correlates with their different sensitivity to hyperoxidation. This kinetic pause opens different pathways on redox signaling for these isoforms. The longer lifetime of PRDX2 sulfenic acid allows it to react with other protein thiols to translate the signal via an intermediate mixed disulfide (involving its peroxidatic cysteine), whereas PRDX1 continues the cycle forming disulfide involving its resolving cysteine to function as a redox relay. In addition, the presence of C83 on PRDX1 imparts a difference on peroxidase activity upon peroxynitrite exposure that needs further study. 相似文献
76.
Gopinath Chattopadhyay Raghavan Varadarajan 《Protein science : a publication of the Protein Society》2019,28(6):1127-1134
With advancements in high‐throughput generation of phenotypic data on mutant proteins, it has become important to individually characterize different proteins or their variants rapidly and with minimal sample consumption. We have made use of a nano differential scanning fluorimetric device, from NanoTemper technologies, to rapidly carry out isothermal chemical denaturation and measure folding/unfolding kinetics of proteins and compared these to corresponding data obtained from conventional spectrofluorimetry. We show that using sample volumes 10‐50‐fold lower than with conventional fluorimetric techniques, one can rapidly and accurately measure thermodynamic and kinetic stability, as well as folding/unfolding kinetics. This method also facilitates characterization of proteins that are difficult to express and purify. 相似文献
77.
78.
Jiaojiao Deng Xiaoliang Yu Xianying Qin Dong Zhou Lihan Zhang Huan Duan Feiyu Kang Baohua Li Guoxiu Wang 《Liver Transplantation》2019,9(14)
Transition metal oxides hold great promise as high‐energy anodes in next‐generation lithium‐ion batteries. However, owing to the inherent limitations of low electronic/ionic conductivities and dramatic volume change during charge/discharge, it is still challenging to fabricate practically viable compacted and thick TMO anodes with satisfactory electrochemical performance. Herein, with mesoporous cobalt–boride nanoflakes serving as multifunctional bridges in ZnCo2O4 micro‐/nanospheres, a compacted ZnCo2O4/Co–B hybrid structure is constructed. Co–B nanoflakes not only bridge ZnCo2O4 nanoparticles and function as anchors for ZnCo2O4 micro‐/nanospheres to suppress the severe volume fluctuation, they also work as effective electron conduction bridges to promote fast electron transportation. More importantly, they serve as Li+ transfer bridges to provide significantly boosted Li+ diffusivity, evidenced from both experimental kinetics analysis and density functional theory calculations. The mesopores within Co–B nanoflakes help overcome the large Li+ diffusion barriers across 2D interfaces. As a result, the ZnCo2O4/Co–B electrode delivers high gravimetric/volumetric/areal capacities of 995 mAh g?1/1450 mAh cm?3/5.10 mAh cm?2, respectively, with robust rate capability and long‐term cyclability. The distinct interfacial design strategy provides a new direction for designing compacted conversion‐type anodes with superior lithium storage kinetics and stability for practical applications. 相似文献
79.
Shangcong Sun Guoqiang Shen Jiawei Jiang Wenbo Mi Xianlong Liu Lun Pan Xiangwen Zhang Ji‐Jun Zou 《Liver Transplantation》2019,9(30)
Solar‐driven water splitting is in urgent need for sustainable energy research, for which accelerating oxygen evolution kinetics along with charge migration is the key issue. Herein, Mn3+ within π‐conjugated carbon nitride (C3N4) in form of Mn–N–C motifs is coordinated. The spin state (eg orbital filling) of Mn centers is regulated by controlling the bond strength of Mn–N. It is demonstrated that Mn serves as intrinsic oxygen evolution reaction (OER) site and the kinetics is dependent on its spin state with an optimized eg occupancy of ≈0.95. Specifically, the governing role of eg occupancy originates from the varied binding strength between Mn and OER intermediates. Benefiting from the rapid spin state‐mediated OER kinetics, as well as extended optical absorption (to 600 nm) and accelerated charge separation by intercalated metal‐to‐ligand state, Mn–C3N4 stoichiometrically splits pure water with H2 production rate up to 695.1 µmol g?1 h?1 under simulated sunlight irradiation (AM1.5), and achieves an apparent quantum efficiency of 4.0% at 420 nm, superior to most solid‐state based photocatalysts to date. This work for the first time correlates photocatalytic redox kinetics with the spin state of active sites, and suggests a nexus between photocatalysis and spin theory. 相似文献
80.
Streblus asper Lour. (Moraceae) is a medicinal plant in Asian countries including India and Thailand, possessing activities of anti-tumor, anti-allergy, anti-parasitic and anti-bacterial. In this paper, characterization, quantitation and similarity evaluation of cardiac glycosides in different parts of S. asper were investigated by HPLC-Q-TOF-MS and chemometric methods. Then, the inhibition of Na+,K+-ATPase activity by the compounds isolated from S. asper was measured. Meanwhile, enzyme kinetics and molecular docking were determined to exhibit the combination modes between cardiac glycosides and Na+,K+-ATPase. As a result, twenty peaks of cardiac glycosides were assigned. Strophanthidin-3-O-α-l-rhamnopyranosyl-(1 → 4)-6-deoxy-β-d-allopyranoside (1), glucostrebloside (2), strebloside (4) and mansonin (8) with a significant activity of inhibiting Na+,K+-ATPase (IC50 7.55–13.60 μM) were chosen for the determination of enzyme kinetics, exhibiting anticompetitive inhibitory characteristics towards Na+,K+-ATPase. Compound 4 could reasonably bind to the active sites of Na+,K+-ATPase, proved by molecular docking. Furthermore, the contents of the major compounds in four different parts of S. asper were extremely different, analyzed by chemometric methods, similarity analysis and principle compounds analysis. All these findings indicated that the contents of major compounds in different parts of S. asper were extremely different with a significant activity of inhibiting Na+,K+-ATPase, providing a reference for determination of effective part and administered dosage. The combination modes between cardiac glycosides and Na+,K+-ATPase were also revealed by enzyme kinetics and molecular docking, which provided a basis for further study of pharmacological activity. 相似文献