A Unique Mode of Coenzyme A Binding to the Nucleotide Binding Pocket of Human Metastasis Suppressor NME1

Coenzyme A (CoA) is a key cellular metabolite which participates in diverse metabolic pathways, regulation of gene expression and the antioxidant defense mechanism. Human NME1 (hNME1), which is a moonlighting protein, was identified as a major CoA-binding protein. Biochemical studies showed that hNME1 is regulated by CoA through both covalent and non-covalent binding, which leads to a decrease in the hNME1 nucleoside diphosphate kinase (NDPK) activity. In this study, we expanded the knowledge on previous findings by focusing on the non-covalent mode of CoA binding to the hNME1. With X-ray crystallography, we solved the CoA bound structure of hNME1 (hNME1-CoA) and determined the stabilization interactions CoA forms within the nucleotide-binding site of hNME1. A hydrophobic patch stabilizing the CoA adenine ring, while salt bridges and hydrogen bonds stabilizing the phosphate groups of CoA were observed. With molecular dynamics studies, we extended our structural analysis by characterizing the hNME1-CoA structure and elucidating possible orientations of the pantetheine tail, which is absent in the X-ray structure due to its flexibility. Crystallographic studies suggested the involvement of arginine 58 and threonine 94 in mediating specific interactions with CoA. Site-directed mutagenesis and CoA-based affinity purifications showed that arginine 58 mutation to glutamate (R58E) and threonine 94 mutation to aspartate (T94D) prevent hNME1 from binding to CoA. Overall, our results reveal a unique mode by which hNME1 binds CoA, which differs significantly from that of ADP binding: the α- and β-phosphates of CoA are oriented away from the nucleotide-binding site, while 3′-phosphate faces catalytic histidine 118 (H118). The interactions formed by the CoA adenine ring and phosphate groups contribute to the specific mode of CoA binding to hNME1

Collaborative Localization in Wireless Sensor Networks via Pattern Recognition in Radio Irregularity Using Omnidirectional Antennas

In recent years, various received signal strength (RSS)-based localization estimation approaches for wireless sensor networks (WSNs) have been proposed. RSS-based localization is regarded as a low-cost solution for many location-aware applications in WSNs. In previous studies, the radiation patterns of all sensor nodes are assumed to be spherical, which is an oversimplification of the radio propagation model in practical applications. In this study, we present an RSS-based cooperative localization method that estimates unknown coordinates of sensor nodes in a network. Arrangement of two external low-cost omnidirectional dipole antennas is developed by using the distance-power gradient model. A modified robust regression is also proposed to determine the relative azimuth and distance between a sensor node and a fixed reference node. In addition, a cooperative localization scheme that incorporates estimations from multiple fixed reference nodes is presented to improve the accuracy of the localization. The proposed method is tested via computer-based analysis and field test. Experimental results demonstrate that the proposed low-cost method is a useful solution for localizing sensor nodes in unknown or changing environments

State owned enterprises as bribe payers: the role of institutional environment

Our paper draws attention to a neglected channel of corruption—the bribe payments by state-owned enterprises (SOEs). This is an important phenomenon as bribe payments by SOEs fruitlessly waste national resources, compromising public welfare and national prosperity. Using a large dataset of 30,249 firms from 50 countries, we show that, in general, SOEs are less likely to pay bribes for achieving organizational objectives owing to their political connectivity. However, in deteriorated institutional environments, SOEs may be subjected to potential managerial rent-seeking behaviors, which disproportionately increase SOE bribe propensity relative to privately owned enterprises. Specifically, our findings highlight the importance of fostering democracy and rule of law, reducing prevalence of corruption and shortening power distance in reducing the incidence of SOE bribery

MICROSTRUCTURE, TEXTURE AND MECHANICAL PROPERTIES OF THE MAGNESIUM ALLOY AZ31 PROCESSED BY ECAP

To investigate the influence of equal channel angular pressing on the microstructure and texture of the magnesium alloy AZ31, electron backscattering diffraction and well as neutron diffraction experiments were carried out. Through these experiments it was possible to trace the microstructure and texture evolution with strain accumulated with the increasing number of equal channel angular pressing passes. It was further demonstrated by subsequent compression tests that the microstructural changes produced by equal channel angular pressing have a beneficial effect on both the compressive strength and ductility of AD31.X113634sciescopu

A Unique Mode of Coenzyme A Binding to the Nucleotide Binding Pocket of Human Metastasis Suppressor NME1

Coenzyme A (CoA) is a key cellular metabolite which participates in diverse metabolic pathways, regulation of gene expression and the antioxidant defense mechanism. Human NME1 (hNME1), which is a moonlighting protein, was identified as a major CoA-binding protein. Biochemical studies showed that hNME1 is regulated by CoA through both covalent and non-covalent binding, which leads to a decrease in the hNME1 nucleoside diphosphate kinase (NDPK) activity. In this study, we expanded the knowledge on previous findings by focusing on the non-covalent mode of CoA binding to the hNME1. With X-ray crystallography, we solved the CoA bound structure of hNME1 (hNME1-CoA) and determined the stabilization interactions CoA forms within the nucleotide-binding site of hNME1. A hydrophobic patch stabilizing the CoA adenine ring, while salt bridges and hydrogen bonds stabilizing the phosphate groups of CoA were observed. With molecular dynamics studies, we extended our structural analysis by characterizing the hNME1-CoA structure and elucidating possible orientations of the pantetheine tail, which is absent in the X-ray structure due to its flexibility. Crystallographic studies suggested the involvement of arginine 58 and threonine 94 in mediating specific interactions with CoA. Site-directed mutagenesis and CoA-based affinity purifications showed that arginine 58 mutation to glutamate (R58E) and threonine 94 mutation to aspartate (T94D) prevent hNME1 from binding to CoA. Overall, our results reveal a unique mode by which hNME1 binds CoA, which differs significantly from that of ADP binding: the α- and β-phosphates of CoA are oriented away from the nucleotide-binding site, while 3′-phosphate faces catalytic histidine 118 (H118). The interactions formed by the CoA adenine ring and phosphate groups contribute to the specific mode of CoA binding to hNME1.Fil: Tossounian, Maria Armineh. Colegio Universitario de Londres; Reino UnidoFil: Hristov, Stefan Denchev. Colegio Universitario de Londres; Reino UnidoFil: Semelak, Jonathan Alexis. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química, Física de los Materiales, Medioambiente y Energía. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química, Física de los Materiales, Medioambiente y Energía; ArgentinaFil: Yu, Bess Yi Kun. Colegio Universitario de Londres; Reino UnidoFil: Baczynska, Maria. Colegio Universitario de Londres; Reino UnidoFil: Zhao, Yuhan. Colegio Universitario de Londres; Reino UnidoFil: Estrin, Dario Ariel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química, Física de los Materiales, Medioambiente y Energía. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química, Física de los Materiales, Medioambiente y Energía; ArgentinaFil: Trujillo, Madia. Universidad de la República; UruguayFil: Filonenko, Valeriy. Colegio Universitario de Londres; Reino UnidoFil: Gouge, Jerome. Colegio Universitario de Londres; Reino UnidoFil: Gout, Ivan. Colegio Universitario de Londres; Reino Unid