RESUMO
The structure of the sodium/galactose transporter (vSGLT), a solute-sodium symporter (SSS) from Vibrio parahaemolyticus, shares a common structural fold with LeuT of the neurotransmitter-sodium symporter family. Structural alignments between LeuT and vSGLT reveal that the crystallographically identified galactose-binding site in vSGLT is located in a more extracellular location relative to the central substrate-binding site (S1) in LeuT. Our computational analyses suggest the existence of an additional galactose-binding site in vSGLT that aligns to the S1 site of LeuT. Radiolabeled galactose saturation binding experiments indicate that, like LeuT, vSGLT can simultaneously bind two substrate molecules under equilibrium conditions. Mutating key residues in the individual substrate-binding sites reduced the molar substrate-to-protein binding stoichiometry to ~1. In addition, the related and more experimentally tractable SSS member PutP (the Na(+)/proline transporter) also exhibits a binding stoichiometry of 2. Targeting residues in the proposed sites with mutations results in the reduction of the binding stoichiometry and is accompanied by severely impaired translocation of proline. Our data suggest that substrate transport by SSS members requires both substrate-binding sites, thereby implying that SSSs and neurotransmitter-sodium symporters share common mechanistic elements in substrate transport.
Assuntos
Sistemas de Transporte de Aminoácidos Neutros/química , Proteínas de Escherichia coli/química , Galactose/química , Proteínas da Membrana Plasmática de Transporte de Neurotransmissores/química , Proteínas de Transporte de Sódio-Glucose/química , Sódio/química , Simportadores/química , Sequência de Aminoácidos , Sistemas de Transporte de Aminoácidos Neutros/metabolismo , Sítios de Ligação , Transporte Biológico , Escherichia coli/química , Escherichia coli/metabolismo , Proteínas de Escherichia coli/metabolismo , Galactose/metabolismo , Cinética , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Dados de Sequência Molecular , Proteínas da Membrana Plasmática de Transporte de Neurotransmissores/metabolismo , Ligação Proteica , Dobramento de Proteína , Estrutura Secundária de Proteína , Estrutura Terciária de Proteína , Proteínas Recombinantes/química , Proteínas Recombinantes/metabolismo , Alinhamento de Sequência , Sódio/metabolismo , Proteínas de Transporte de Sódio-Glucose/metabolismo , Homologia Estrutural de Proteína , Especificidade por Substrato , Simportadores/metabolismo , Termodinâmica , Vibrio parahaemolyticus/química , Vibrio parahaemolyticus/metabolismoRESUMO
The aim of this study was to assess the quality of life (QOL) and the severity of depression in people living with HIV/AIDS (PLWHA) and investigate its correlates. This was a cross-sectional study on 700 PLWHA in India. World Health Organization QOL HIV (WHOQOL HIV-BREF) and Patient Health Questionnaire-9 (PHQ-9) were used to assess QOL and depression in PLWHA, respectively. The study population was divided into five groups on the basis of Cluster of Differentiation 4 (CD4) count as follows: Group A [< 50 cells/µL], Group B [50-199 cells/µL], Group C [200-349 cells/µL], Group D [350-499 cells/µL], and Group E [>500 cells/µL]. The lowest mean scores were noted under Group A [< 50 cells/µL] in physical and psychological domains and the highest mean scores were noted under Group E [> 500 cells/µL] in physical and environment domains. PHQ9 scores negatively correlated with QOL domains and the correlation was statistically significant (p < 0.001) with the highest negative correlation was found in relation to the psychological domain (r = -0.739). The PHQ9 score in those who do not have opportunistic illnesses (7.23 ± 6.14) was lower in comparison to those who had opportunistic illnesses (9.81 ± 6.40) and the difference was statistically significant (p < 0.001). We observed that there was almost a chronological increase in the individual QOL domain score and a decrease in the PHQ9 score with an increase in CD4 count. Our result supports the implementation of routine screening for depression in antiretroviral therapy centers and multidisciplinary interventions to improve outcomes among depressed PLWHA.
Assuntos
Infecções por HIV , Qualidade de Vida , Estudos Transversais , Depressão/epidemiologia , Depressão/etiologia , Infecções por HIV/complicações , Infecções por HIV/epidemiologia , Humanos , Índia/epidemiologia , Inquéritos e QuestionáriosRESUMO
The Monte Carlo code SIMIND is used in nuclear medicine for research purposes, and also for testing the validity of various applications. Conversion of a SIMIND-generated interfile (header and image data file) is required to process the simulated image data on a Xeleris workstation. Currently there is no conversion program provided with SIMIND to convert its interfile, which is acceptable in any nuclear medicine workstation. Manual editing of the header file is possible with any standard text editor but it is time-consuming (requiring â¼1 h) and stressful. To alleviate this, we have developed a conversion program using FreeMat V4.0 (an open source software similar to MATLAB from MathWorks). It takes an average of 0.04404 s to convert a SIMIND SPECT data interfile and make it acceptable to Xeleris.