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1.
Cell ; 141(3): 446-57, 2010 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-20434985

RESUMO

The CED-4 homo-oligomer or apoptosome is required for initiation of programmed cell death in Caenorhabditis elegans by facilitating autocatalytic activation of the CED-3 caspase zymogen. How the CED-4 apoptosome assembles and activates CED-3 remains enigmatic. Here we report the crystal structure of the complete CED-4 apoptosome and show that it consists of eight CED-4 molecules, organized as a tetramer of an asymmetric dimer via a previously unreported interface among AAA(+) ATPases. These eight CED-4 molecules form a funnel-shaped structure. The mature CED-3 protease is monomeric in solution and forms an active holoenzyme with the CED-4 apoptosome, within which the protease activity of CED-3 is markedly stimulated. Unexpectedly, the octameric CED-4 apoptosome appears to bind only two, not eight, molecules of mature CED-3. The structure of the CED-4 apoptosome reveals shared principles for the NB-ARC family of AAA(+) ATPases and suggests a mechanism for the activation of CED-3.


Assuntos
Proteínas de Caenorhabditis elegans/química , Caenorhabditis elegans/metabolismo , Proteínas de Ligação ao Cálcio/química , Sequência de Aminoácidos , Animais , Apoptossomas/metabolismo , Fator Apoptótico 1 Ativador de Proteases/metabolismo , Caenorhabditis elegans/química , Caspases/química , Cristalografia por Raios X , Modelos Moleculares , Alinhamento de Sequência , Difração de Raios X
2.
Small ; : e2308530, 2023 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-38059871

RESUMO

Metal single-atom catalysts (M-SACs) attract extraordinary attention for promoting oxygen reduction reaction (ORR) with 100% atomic utilization. However, low metal loading (usually less than 2 wt%) limits their overall catalytic performance. Herein, a hierarchical-structure-stabilization strategy for fabricating high-loading (18.3%) M-SACs with efficient ORR activity is reported. Hierarchical pores structure generated with high N content by SiO2 can provide more coordination sites and facilitate the adsorption of Fe3+ through mesoporous and confinement effect of it stabilizes Fe atoms in micropores on it during pyrolysis. High N content on hierarchical pores structure could provide more anchor sites of Fe atoms during the subsequent secondary pyrolysis and synthesize the dense and accessible Fe-N4 sites after subsequent pyrolysis. In addition, Se power is introduced to modulate the electronic structure of Fe-N4 sites and further decrease the energy barrier of the ORR rate-determining step. As a result, the Fe single atom catalyst delivers unprecedentedly high ORR activity with a half-wave potential of 0.895 V in 0.1 M KOH aqueous solution and 0.791 V in 0.1 M HClO4 aqueous solution. Therefore, a hierarchical-pore-stabilization strategy for boosting the density and accessibility of Fe-N4 species paves a new avenue toward high-loading M-SACs for various applications such as thermocatalysis and photocatalysis.

3.
Proc Natl Acad Sci U S A ; 111(46): 16254-61, 2014 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-25313070

RESUMO

Autocatalytic activation of an initiator caspase triggers the onset of apoptosis. In dying cells, caspase-9 activation is mediated by a multimeric adaptor complex known as the Apaf-1 apoptosome. The molecular mechanism by which caspase-9 is activated by the Apaf-1 apoptosome remains largely unknown. Here we demonstrate that the previously reported 1:1 interaction between Apaf-1 caspase recruitment domain (CARD) and caspase-9 CARD is insufficient for the activation of caspase-9. Rather, formation of a multimeric CARD:CARD assembly between Apaf-1 and caspase-9, which requires three types of distinct interfaces, underlies caspase-9 activation. Importantly, an additional surface area on the multimeric CARD assembly is essential for caspase-9 activation. Together, these findings reveal mechanistic insights into the activation of caspase-9 by the Apaf-1 apoptosome and support the induced conformation model for initiator caspase activation by adaptor complexes.


Assuntos
Proteínas Reguladoras de Apoptose/química , Apoptossomas/metabolismo , Caspase 9/química , Proteínas Reguladoras de Apoptose/genética , Proteínas Reguladoras de Apoptose/metabolismo , Caspase 9/metabolismo , Catálise , Ativação Enzimática , Humanos , Ligação de Hidrogênio , Técnicas In Vitro , Lisina/química , Modelos Químicos , Modelos Moleculares , Mutagênese Sítio-Dirigida , Conformação Proteica , Mapeamento de Interação de Proteínas , Estrutura Secundária de Proteína , Estrutura Terciária de Proteína , Proteínas Recombinantes de Fusão/química , Proteínas Recombinantes de Fusão/metabolismo
4.
Carbohydr Polym ; 236: 116094, 2020 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-32172896

RESUMO

Different size and morphology monodispersed chitosan (CS) microspheres loaded with the anticancer drug of 5-fluorouracil (5-Fu) were prepared by the microfluidic method assisted by a crosslinking unit with crosslinkers of tripolyphosphate (TPP) and glutaraldehyde (GTA). The sizes, morphologies, drug loading, encapsulation efficiency, drug release and cytotoxicity of 5-Fu loaded CS microspheres were characterized and determined. Results indicated that the CS microspheres were uniform in size distributions. They possessed excellent encapsulation efficiency and drug loading. The TPP-crosslinked CS microspheres had rough surfaces and exhibited faster drug release, whereas the CS microspheres crosslinked with GTA had smooth surfaces and showed slower drug release. Furthermore, 5-Fu-loaded CS microspheres exhibited sustained drug release which well fitted the first-order kinetics model and were pH-responsive in that the drug cumulative release was greater at acidic environments than at neutral conditions. Finally, 5-Fu loaded CS microspheres provided sufficient cytotoxicity and were satisfactory in the cancer cell inhibition.


Assuntos
Antimetabólitos Antineoplásicos/farmacologia , Quitosana/química , Portadores de Fármacos/química , Fluoruracila/farmacologia , Microesferas , Antimetabólitos Antineoplásicos/química , Sobrevivência Celular/efeitos dos fármacos , Reagentes de Ligações Cruzadas/química , Liberação Controlada de Fármacos , Fluoruracila/química , Glutaral/química , Células Hep G2 , Humanos , Concentração de Íons de Hidrogênio , Cinética , Dispositivos Lab-On-A-Chip , Microfluídica/instrumentação , Microfluídica/métodos , Polifosfatos/química
5.
ACS Omega ; 4(14): 16166-16170, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31592483

RESUMO

In the present work, the oxidation stability of blends of methyl oleate, zinc dialkyldithiophosphate (ZDDP), and a high viscosity index mineral base oil was determined by the method of a rotating pressure vessel, while the antiwear abilities were evaluated on a four-ball friction tester. Thereafter, the thermal decomposition characteristics and oxidation products of the oxidized blends were analyzed by a thermogravimetric analyzer and a gas chromatograph coupled to a mass spectrometer, respectively. The results showed that the antioxidation ability of ZDDP was substantially improved by methyl oleate, while the antiwear capacity is markedly impaired by methyl oleate. Furthermore, the thermal decomposition characteristics and oxidation products of ZDDP-containing oils were altered by methyl oleate. The present study evidently convinced that chemical interactions between ZDDP and methyl oleate had occurred, which were attributed to the increased antioxidation ability and decreased antiwear capacity of ZDDP in oils contaminated with methyl oleate.

6.
Se Pu ; 20(2): 140-3, 2002 Mar.
Artigo em Zh | MEDLINE | ID: mdl-12541971

RESUMO

A rapid and simple method for the study of the acupuncture effect on monoamine transmitters and related compounds in rabbit plasma and brain tissue by high performance liquid chromatography with electrochemical detection was developed. An ODS column was selected as the separation column at 25 degrees C, and pH 4.50, 0.02 mol/L of trisodium citrate-0.05 mol/L sodium phosphate dibasic to methanol (95:5, volume ratio) without ion-pair at a flow rate of 1.0 mL/min. Four compounds, epinephrine (E), norepinephrine (NE), dopamine (DA) and 5-hydroxytryptamine (5-HT), were simultaneously separated and determined under the above conditions. Twenty rabbits were investigated after the acupuncture action upon the central neurotransmitters. The sufficient data showed that acupuncture could significantly affect the activities of the neurotransmitters including E, NE, DA and 5-HT, and the changed functions of the neurotransmitter systems induced by acupuncture not only lead to the neurotransmitter content increase both in brain and plasma but also cause the increase of rabbit breed ability. The results show that the method is very simple and fast. The method is valuable not only for clinical diagnosis but also for research work.


Assuntos
Monoaminas Biogênicas/metabolismo , Encéfalo/metabolismo , Eletroacupuntura , Animais , Monoaminas Biogênicas/sangue , Cromatografia Líquida de Alta Pressão/métodos , Dopamina/metabolismo , Eletroquímica , Epinefrina/metabolismo , Feminino , Norepinefrina/metabolismo , Coelhos , Serotonina/metabolismo
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