Amino Acid Enzymes and Metabolism

Development of a NanoBRET assay platform to detect intracellular target engagement in living cells for the Glycine Transporter 1 (SLC6A9)

The paper develops a NanoBRET assay to quantify intracellular GlyT1 target engagement in living cells, distinguishing intracellular from extracellular ligands and resolving structure-activity relationships.

Probing the interaction between the WDR41 7CD loop of the C9ORF72 complex and purified PQLC2

This study characterizes the interaction between PQLC2 and the WDR41 7CD loop using EPR spectroscopy, revealing structural and dynamic insights into their binding mechanism.

N-Acetylaspartate Synthesis as a Thermodynamic Relief Mechanism for Mitochondrial Aspartate Aminotransferase

The paper models mitochondrial aspartate metabolism to show that NAA synthesis by ASPNAT relieves thermodynamic constraints on AAT under low OAA conditions.

Structural basis of substrate recognition and allosteric inhibition in human B0AT2

This study determines cryo-EM structures of B0AT2 to elucidate substrate recognition and allosteric inhibition mechanisms, revealing conserved intracellular cavities across SLC6 transporters.

Dynamic Gating Mechanism of the b0,+AT-Mediated Arg Transport: Insights from ASMD Simulations

This paper identifies residue W230 as a dynamic gate in b0,+AT that regulates arginine transport through side chain flipping, using molecular dynamics simulations.

Asparagine availability differentially regulates early vs late CD4+ and CD8+ T cell activation, metabolism and autophagy

This study shows CD4+ T cells rely more on asparagine uptake than CD8+ T cells for activation, differentiation, metabolism, and autophagy, with CD8+ cells expressing more ASNS.

Histidine exchange sustains LAT1 activity and proliferation in glutamine-addicted breast cancers.

The paper identifies histidine as a key substrate for LAT1 that supports mTORC1 signaling and proliferation in glutamine-addicted breast cancers, revealing a metabolic vulnerability.

Conformational Remodeling Underlies Activity Loss in Disease-Linked Asparagine Synthetase Variant

This study investigates how a specific mutation in the ASNS gene impairs enzyme function by disrupting conformational dynamics, using biochemical, cryo-EM, and molecular dynamics approaches.

Effect of Age and Sex on BCAA Metabolism in Mice

This study examines how age and sex influence BCAA metabolism in mice, finding sex- and age-specific differences in BCAA and BCKA levels and enzyme activity across tissues.

pH-dependent regulation in SLC38A9

This study shows that SLC38A9, a lysosomal amino acid transporter, has pH-dependent arginine uptake regulated by the histidine residue His544, which influences transport through protonation/deprotonation rather than direct substrate binding.

Cryo-EM reveals how ASX-173 inhibits human asparagine synthetase to activate the integrated stress response

The paper describes how ASX-173 inhibits asparagine synthetase, induces the integrated stress response, and reduces cell growth in HEK-293A cells.

Combining Selenocystine Based Fluorescence Assay with Structural Prediction for Enhanced Detection and Analysis of Cystine Stone Pathology

The paper develops a nonradioactive assay combining selenocystine fluorescence and AlphaFold for diagnosing cystinuria mutations and analyzing their functional impacts.

Methionine γ-lyase Traps Cofactor Pyridoxal-5'-phosphate through Specific Serine-Mediated Affinity

This study identifies a conserved serine in the C-terminal domain of MGL that mediates specific PLP binding and catalytic efficiency.

The ASNS inhibitor ASX-173 potentiates L-asparaginase anticancer activity

The paper identifies ASX-173 as a potent ASNS inhibitor that enhances the anti-cancer effects of L-asparaginase in leukemia and shows its potential across multiple cancer types.

Mechanism and Structure-Guided Optimization of SLC1A1/EAAT3-Selective Inhibitors in Kidney Cancer

This study determines the cryo-EM structure of SLC1A1 bound to an inhibitor, identifies its binding mechanism, and develops improved inhibitors with enhanced cytotoxicity in kidney cancer cells.

Sideroflexins enable mitochondrial transport and metabolism of neutral amino acids

The paper identifies sideroflexins as mitochondrial transporters for neutral amino acids and shows functional overlap among paralogues.

Dysregulation of Multiple Solute Carrier genes and Metabolic Deficits in SLC1A4-Mutant Human iPSC-Derived Hippocampal Neurons

This study investigates SLC1A4 mutations in human iPSC-derived neurons, revealing metabolic and synaptic deficits linked to amino acid transport dysfunction and neurodevelopmental disorders.

An intercellular metabolic relay for brain sparingin Drosophila

The paper identifies an intercellular metabolic relay involving glutamine and glutamate that sustains neural stem cell proliferation during brain sparing in Drosophila.

Identification and characterization of potent and selective inhibitors for the B0AT2/SLC6A15 amino acid transporter

This study identifies and characterizes the first inhibitors of the B0AT2/SLC6A15 amino acid transporter, showing potent and selective inhibition with effects on neurite outgrowth.

D-serine suppresses one-carbon metabolism by competing with mitochondrial L-serine transport

This study shows D-serine competes with mitochondrial L-serine transport, suppressing one-carbon metabolism and affecting neural cell proliferation.

Glutamine-addiction in cisplatin resistant cancer cells is mediated by SLC7A11 and can be targeted with asparaginase therapy

This study identifies SLC7A11 as a mediator of cisplatin resistance in cancer cells and shows asparaginase therapy can target this resistance.

Comparative analysis of Lysine and Arginine biosynthesis pathway in Deinococcus genomes

The paper compares L-lysine and L-arginine biosynthesis pathways in 23 Deinococcus genomes, identifying structural variations and potential functional divergence.

Structural insights into human excitatory amino acid transporter EAAT2

This study reports cryo-EM structures of human EAAT2 in substrate-free and inhibitor-bound states, revealing structural features and the mechanism of selective inhibition.

A unified model of amino acid homeostasis in mammalian cells

The paper develops a computational model to simulate amino acid translocation and demonstrates its ability to predict cytosolic concentrations in cancer cell lines and myotubes.

Dietary and pharmacological induction of serine synthesis genes

The paper investigates strategies to induce serine synthesis genes through dietary and pharmacological interventions, finding that low protein and ketogenic diets, as well as certain medications, increase their expression in the liver and brain.