The oxyanion-translocating ATPase encoded by the plasmid-borne ars operon catalyzes extrusion of antimonials and arsenicals from cells of Escherichia coli, thus providing resistance to those toxic oxyanions. The purified catalytic subunit of the ATPase, the ArsA protein, exhibits oxyanion-stimulated ATPase activity. The nature of the oxyanion binding site was probed by reaction with the fluorescent sulfhydryl probe 2-(4'-maleimidoanilino)naphthalene-6-sulfonic acid (MIANS). Our results indicate that MIANS reacts with the ArsA protein in an antimonite-dependent manner. After the protein had been modified with MIANS, two of four cysteines in the ArsA protein had reacted with the probe in the absence of the oxyanionic substrate, and three in the presence of antimonite. The quantum yield of the MIANS-ArsA protein adduct was significantly higher if modification of the protein had occurred in the presence of oxyanionic substrates. Thus binding of the anionic substrate of the pump produces a conformational change in the ArsA protein such that a single additional cysteinyl residue reacts more readily with the sulfhydryl probe.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1021/bi00211a051 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
An augmented transformer model trained on protein family specific variant data leads to improved prediction of variants of uncertain significance.
Hum Genet
January 2025
TCS Research, Tata Consultancy Services, Hyderabad, India.
Variants of uncertain significance (VUS) represent variants that lack sufficient evidence to be confidently associated with a disease, thus posing a challenge in the interpretation of genetic testing results. Here we report an improved method for predicting the VUS of Arylsulfatase A (ARSA) gene as part of the Critical Assessment of Genome Interpretation challenge (CAGI6). Our method uses a transfer learning approach that leverages a pre-trained protein language model to predict the impact of mutations on the activity of the ARSA enzyme, whose deficiency is known to cause a rare genetic disorder, metachromatic leukodystrophy.
View Article and Find Full Text PDFRelative Frequency of Metachromatic Leukodystrophy in Egypt: A Reference Laboratory Report.
Front Biosci (Schol Ed)
December 2024
Biochemical Genetics Department, Human Genetics and Genome Research Institute, National Research Centre, 12622 Cairo, Egypt.
Background: Metachromatic leukodystrophy (MLD) is an autosomal recessive hereditary neurodegenerative disease caused by a deficiency in arylsulfatase A (ARSA) activity and belongs to the group of lysosomal storage diseases. A biochemical diagnosis of MLD is based on determining the residual ARSA activity in leukocytes, skin fibroblasts, and urine. This study documents our biochemical experience and estimates the relative frequency of MLD over 21 years (2001-2022).
View Article and Find Full Text PDFMulti-Omics Approach Reveals Genes and Pathways Affected in Miller-Dieker Syndrome.
Mol Neurobiol
November 2024
Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, IN, 46556, USA.
Miller-Dieker syndrome (MDS) is a rare neurogenetic disorder resulting from a heterozygous deletion of 26 genes in the MDS locus on human chromosome 17. MDS patients often die in utero and only 10% of those who are born reach 10 years of age. Current treatments mostly prevent complications and control seizures.
View Article and Find Full Text PDFNanoparticles encapsulating phosphatidylinositol derivatives promote neuroprotection and functional improvement in preclinical models of ALS via a long-lasting activation of TRPML1 lysosomal channel.
Pharmacol Res
December 2024
Department of Biomedical Sciences and Public Health, School of Medicine, University "Politecnica Delle Marche", Via Tronto 10/A, Ancona 60126, Italy. Electronic address:
Article Synopsis
- Amyotrophic lateral sclerosis (ALS) is a progressive and currently incurable neurodegenerative disease characterized by the loss of motor neurons, muscle atrophy, and cellular dysfunction related to protein aggregation and calcium imbalances.
- Researchers have identified autophagy dysfunction as a key area for potential ALS treatment, with TRPML1 being a crucial lysosomal channel that, when properly stimulated, can aid in this process.
- A new lipid-based formulation of PI(3,5)P was developed to effectively stabilize TRPML1 activity in ALS models, showing promising results in improving neuromuscular function, reducing motor neuron loss, and extending the lifespan of SOD1 ALS mice by about 10 days.
ARSA Variant Associated With Late Infantile Metachromatic Leukodystrophy and Carrier Rate in Individuals of Ashkenazi Jewish Ancestry.
Am J Med Genet A
October 2024
Clinical Genetic Services, Department of Pediatrics, NYU Grossman School of Medicine, New York, New York, USA.
Metachromatic leukodystrophy (MLD) is a rare neurodegenerative lysosomal storage disease resulting from bi-allelic pathogenic variants in the ARSA gene. MLD is distinguished clinically based on the age of onset into late-infantile, juvenile, and adult. The late-infantile type is the most severe phenotype presenting with hypotonia, weakness, gait abnormalities, which progresses to mental and physical decline leading to early death.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!