ABSTRACT
The adenosine 5'-triphosphate (ATP)-binding cassette (ABC) transporter, IrtAB, plays a vital role in the replication and viability of Mycobacterium tuberculosis (Mtb), where its function is to import iron-loaded siderophores. Unusually, it adopts the canonical type IV exporter fold. Herein, we report the structure of unliganded Mtb IrtAB and its structure in complex with ATP, ADP, or ATP analogue (AMP-PNP) at resolutions ranging from 2.8 to 3.5 Å. The structure of IrtAB bound ATP-Mg2+ shows a "head-to-tail" dimer of nucleotide-binding domains (NBDs), a closed amphipathic cavity within the transmembrane domains (TMDs), and a metal ion liganded to three histidine residues of IrtA in the cavity. Cryo-electron microscopy (Cryo-EM) structures and ATP hydrolysis assays show that the NBD of IrtA has a higher affinity for nucleotides and increased ATPase activity compared with IrtB. Moreover, the metal ion located in the TM region of IrtA is critical for the stabilization of the conformation of IrtAB during the transport cycle. This study provides a structural basis to explain the ATP-driven conformational changes that occur in IrtAB.
Subject(s)
Siderophores/metabolism , Iron/metabolism , Mycobacterium tuberculosis/metabolism , Cryoelectron Microscopy , Adenosine Triphosphate/metabolism , ATP-Binding Cassette TransportersABSTRACT
Amino acids are important compounds with a wide range of applications in the food, medicine and chemical industries. Corynebacterium glutamicum is a powerful workhorse commonly used in industrial amino acid production, with the scale of more than one million tons. In addition to its efficient anabolism, the effective exporters also ensure the high amino acid production by C. glutamicum. In this review, the research progress of amino acid exporter of C. glutamicum is summarized, to provide the foundation for further improving amino acid production by C. glutamicum via metabolic engineering.
Subject(s)
Amino Acids , Corynebacterium glutamicum/genetics , Metabolic EngineeringABSTRACT
Zinc has been considered as a vital constituent of proteins, including enzymes. Mobile reactive zinc (Zn2+) is the key form of zinc involved in signal transductions, which are mainly driven by its binding to proteins or the release of zinc from proteins, possibly via a redox switch. There has been growing evidence of zinc's critical role in cell signaling, due to its flexible coordination geometry and rapid shifts in protein conformation to perform biological reactions. The importance and complexity of Zn2+ activity has been presumed to parallel the degree of calcium's participation in cellular processes. Whole body and cellular Zn2+ levels are largely regulated by metallothioneins (MTs), Zn2+ importers (ZIPs), and Zn2+ transporters (ZnTs). Numerous proteins involved in signaling pathways, mitochondrial metabolism, and ion channels that play a pivotal role in controlling cardiac contractility are common targets of Zn2+. However, these regulatory actions of Zn2+ are not limited to the function of the heart, but also extend to numerous other organ systems, such as the central nervous system, immune system, cardiovascular tissue, and secretory glands, such as the pancreas, prostate, and mammary glands. In this review, the regulation of cellular Zn2+ levels, Zn2+-mediated signal transduction, impacts of Zn2+ on ion channels and mitochondrial metabolism, and finally, the implications of Zn2+ in health and disease development were outlined to help widen the current understanding of the versatile and complex roles of Zn2+.
Subject(s)
Central Nervous System , Heart , Immune System , Ion Channels , Mammary Glands, Human , Metabolism , Metallothionein , Oxidation-Reduction , Pancreas , Prostate , Protein Conformation , Signal Transduction , ZincABSTRACT
Objectives: To develop a computational tool for NEURON simulation environment, user friendly, to store the results generated during simulation and to make subsequent analysis with other tools such as Matlab and IgorPRo Materials and Methods: Data Exporter was implemented in the programming language hoc. This algorithm is divided in 13 sections or blocks. The first section is necessary to edit in a new simulation. These new configuration determine the geometry, biophysic properties the neurons to simulate and path to save data. Results: To check the efficiency of the algorithm, we simulated the propagation of action potential in TRN(thalamic reticular nucleus) neuron in different large of simulation. We determine that the time of simulation is linear respect to time of simulation. Conclusions: Data Exporter makes easier to start to neural simulation in NEURON reducing the steps of programming to geometry and biophysical properties of the neuron and to allow save data to next steps of analysis.
Objetivos: Desarrollar una herramienta computacional en ambiente lenguaje de programación hoc de NEURON y de fácil uso, que permita el rápido almacenamiento de los resultados obtenidos para su posterior análisis en otros software tales como Matlab or IgorPro. Materiales y métodos: Para el desarrollo de Data Exporter se escribió un algoritmo en lenguaje de programación hoc de NEURON. El algoritmo, escrito en un único archivo de texto, esta dividido en 13 bloques, de los cuales solo el primero debe ser modificado para adaptarlo a una geometría y biofísica neuronal particular y para determinar la ruta de almacenamiento de los datos. Resultados: Se desarrollo un software que simula la propagación de potenciales de acción a través de geometrías neuronales complejas. El uso de esta herramienta permite el almacenamiento de los resultados obtenidos, como potenciales y corrientes de membrana en diferentes puntos de toda la neurona, sin incremento significativo en el tiempo para el desarrollo de los procesos. Conclusiones: Data Exporter es un software que le da mayor flexibilidad a NEURON facilitando el acceso a nuevos neurocientíficos, los cuales pueden usarlo con solo conocer los códigos necesarios para el desarrollo de los archivos relacionados con las propiedades geométricas y biofísicas neuronales.