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2.
Nat Metab ; 5(7): 1111-1126, 2023 07.
Artículo en Inglés | MEDLINE | ID: mdl-37349485

RESUMEN

Regulation of CO2 fixation in cyanobacteria is important both for the organism and global carbon balance. Here we show that phosphoketolase in Synechococcus elongatus PCC7942 (SeXPK) possesses a distinct ATP-sensing mechanism, where a drop in ATP level allows SeXPK to divert precursors of the RuBisCO substrate away from the Calvin-Benson-Bassham cycle. Deleting the SeXPK gene increased CO2 fixation particularly during light-dark transitions. In high-density cultures, the Δxpk strain showed a 60% increase in carbon fixation and unexpectedly resulted in sucrose secretion without any pathway engineering. Using cryo-EM analysis, we discovered that these functions were enabled by a unique allosteric regulatory site involving two subunits jointly binding two ATP, which constantly suppresses the activity of SeXPK until the ATP level drops. This magnesium-independent ATP allosteric site is present in many species across all three domains of life, where it may also play important regulatory functions.


Asunto(s)
Dióxido de Carbono , Fotosíntesis , Dióxido de Carbono/metabolismo , Fotosíntesis/fisiología , Ciclo del Carbono , Adenosina Trifosfato/metabolismo
3.
Mar Drugs ; 16(11)2018 Oct 25.
Artículo en Inglés | MEDLINE | ID: mdl-30366389

RESUMEN

Memory retrieval dysfunction is a symptom of schizophrenia, autism spectrum disorder (ASD), and absence epilepsy (AE), as well as an early sign of Alzheimer's disease. To date, few drugs have been reported to enhance memory retrieval. Here, we found that a coral-derived natural product, excavatolide-B (Exc-B), enhances contextual memory retrieval in both wild-type and Cav3.2-/- mice via repressing the delayed rectifier potassium current, thus lowering the threshold for action potential initiation and enhancing induction of long-term potentiation (LTP). The human CACNA1H gene encodes a T-type calcium channel (Cav3.2), and its mutation is associated with schizophrenia, ASD, and AE, which are all characterized by abnormal memory function. Our previous publication demonstrated that Cav3.2-/- mice exhibit impaired contextual-associated memory retrieval, whilst their retrieval of spatial memory and auditory cued memory remain intact. The effect of Exc-B on enhancing the retrieval of context-associated memory provides a hope for novel drug development.


Asunto(s)
Canales de Potasio de Tipo Rectificador Tardío/antagonistas & inhibidores , Diterpenos/farmacología , Hipocampo/efectos de los fármacos , Memoria/efectos de los fármacos , Animales , Conducta Animal , Canales de Calcio Tipo T/genética , Condicionamiento Psicológico/efectos de los fármacos , Canales de Potasio de Tipo Rectificador Tardío/metabolismo , Espinas Dendríticas/efectos de los fármacos , Miedo/psicología , Hipocampo/metabolismo , Potenciación a Largo Plazo/efectos de los fármacos , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Cultivo Primario de Células
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