Biochemical and Molecular Research

Exploring the multi-protein assembly of the enzymes of the de novo purine nucleotide biosynthetic pathway from Pseudomonas aeruginosa

This study investigates the structural and functional organization of the de novo purine nucleotide biosynthetic pathway enzymes in Pseudomonas aeruginosa, revealing a metabolon-like complex with potential antibiotic implications.

Rate Limiting Enzymes in Nucleotide Metabolism Synchronize Nucleotide Biosynthesis and Chromatin Formation

This study identifies PRPS-PRPSAP complexes as regulators of histone chaperone interactions, linking nucleotide biosynthesis to chromatin assembly.

NUDT5 regulates the global efficacy of nucleoside analog drugs by coordinating purine synthesis and PRPP allocation

This study shows NUDT5 regulates the effectiveness of nucleoside analog drugs by coordinating purine synthesis and PRPP allocation through its interaction with PPAT.

De Novo Hepatic Pyrimidine Synthesis Regulates Systemic Energy Homeostasis

This study shows that reduced hepatic pyrimidine synthesis during fasting and obesity promotes insulin resistance and obesity by increasing hepatic glucose production and decreasing insulin clearance.

NUDT5 regulates purine metabolism and thiopurine sensitivity by interacting with PPAT

This study identifies NUDT5 as a regulator of purine metabolism and thiopurine sensitivity by interacting with PPAT, independent of its known enzymatic activity.

Catalytic Mechanism and Differential Alarmone Regulation of a Conserved Stringent Nucleosidase

This study investigates how the alarmones ppGpp and pppGpp differentially regulate the nucleosidase PpnN in E. coli, revealing its role in bacterial survival under antibiotic stress and uncovering a conserved catalytic mechanism shared with plant cytokinin signaling proteins.

Succinate dehydrogenase activity supports de novo purine synthesis

This study shows that succinate dehydrogenase supports de novo purine synthesis in cancer cells, and its inhibition reduces proliferation by impairing purine biosynthesis and inducing a compensatory salvage pathway.

Purine nucleotides are competitive inhibitors of apo-GOT1

The paper identifies purine nucleotides as competitive inhibitors of apo-GOT1 by showing they bind to the PLP pocket and destabilize the enzyme in its cofactor-free state.

Preliminary analysis of the metabolic and physical activity profiles of mice lacking the slc43a3-encoded equilibrative nucleobase transporter 1

This study examines the effects of slc43a3 knockout on metabolic and physical activity in mice, finding sex-specific differences in oxygen consumption, circadian rhythms, and blood pressure.

A Novel Allosteric Inhibitor Targeting IMPDH2 at Y233 Overcomes Resistance to Tyrosine Kinase Inhibitors in Lymphoma

Purine nucleobases enhance CD8+ T cell effector function

This study identifies purine nucleobases as immunometabolites that enhance CD8+ T cell effector function by enabling a metabolic switch from de novo synthesis to salvage pathway.

Resilience and vulnerabilities of tumor cells under purine shortage stress

This study investigates how cancer cells adapt to purine shortage stress and identifies vulnerabilities in purine metabolism and microtubules as therapeutic targets.

De novo pyrimidine biosynthesis inhibition synergizes with BCL-XL targeting in pancreatic cancer

This study identifies that combining DHODH inhibition with BCL-XL targeting synergistically induces apoptosis in pancreatic cancer, offering a new combination therapy strategy.

Evolutionary origins and innovations sculpting the mammalian PRPS enzyme complex

This study traces the evolutionary origins of mammalian PRPS genes and shows how their duplication and specialization enable functional multimeric complexes with regulatory features.

Identification of picornavirus proteins that inhibit de novo nucleotide synthesis during infection

This study identifies picornavirus proteins that inhibit de novo nucleotide synthesis during infection using metabolomics and recombinant virus analysis.

Evolutionarily divergent Mycobacterium tuberculosis CTP synthase filaments are under selective pressure

This study shows that Mycobacterium tuberculosis CTP synthase forms unique filaments that stabilize enzyme activity and resist inhibition, with mutations affecting filament formation under positive selection in clinical isolates.

Structural basis of substrate specificity of Helix pomatia AMP deaminase and a chimeric ADGF adenosine deaminase

The paper determines the structure of HPAMPD, a mollusk adenosine deaminase with nucleotide specificity, and shows how it binds the 5-monophosphate group of AMP through specific structural elements.

An IMPDH2 variant associated with neurodevelopmental disorder disrupts purine biosynthesis and somitogenesis

This paper shows that an IMPDH2 variant linked to neurodevelopmental disorders disrupts purine biosynthesis and somitogenesis in Xenopus tropicalis by affecting filament assembly and GTP sensitivity.

Functional profiling reveals a non-enzymatic role of NUDT5 in repressing purine de novo synthesis

The paper identifies a non-enzymatic role of NUDT5 in repressing purine de novo synthesis by scaffolding PPAT, with implications for cancer treatment and MTHFD1 deficiency.

Uridine-sensitized screening identifies genes and metabolic regulators of nucleotide synthesis

The paper identifies genes and metabolic regulators of nucleotide synthesis using uridine salvage and CRISPR-Cas9 screening, revealing NUDT5's role in maintaining nucleotide balance and its impact on chemotherapy resistance.

The monomer/dimer switch modulates the activity of plant adenosine kinase

The paper investigates how the monomer/dimer switch in plant adenosine kinase (ADK) modulates enzyme activity and establishes a negative feedback mechanism to regulate adenosine and AMP levels.

Pathway Coessentiality Mapping Reveals Complex II is Required for de novo Purine Biosynthesis in Acute Myeloid Leukemia

The paper identifies Complex II's role in de novo purine biosynthesis in AML using CRISPR and metabolomic data, showing it as a therapeutic target.

Pyruvate Kinase Directly Generates GTP in Glycolysis, Supporting Growth and Contributing to Guanosine Toxicity

The paper identifies pyruvate kinase's role in GTP synthesis during glycolysis in bacteria, showing it reduces guanosine toxicity and contributes to NTP production.

CTP Drives Human CTPS1 Filamentation

This study identifies CTP as a regulator of hCTPS1 filamentation, revealing its structural basis and evolutionary conservation.

IMPDH Cytoophidia in the Pancreas: Morphological Dynamics and Metabolic Implications

This study examines IMPDH cytoophidia in pancreatic islets under normal and diabetic conditions, showing morphological changes linked to impaired glucose tolerance.

Combined deletion of cytosolic 5'-nucleotidases IA and II lowers glycemia by improving skeletal muscle insulin action and by lowering hepatic glucose production

The paper shows that deleting both NT5C1A and NT5C2 in mice lowers blood sugar by improving muscle insulin response and reducing liver glucose production.

Structural Insights into Broad-Range Polyphosphate Kinase 2 II Enzymes Applicable for Pyrimidine Nucleoside Diphosphate Synthesis

This study characterizes two PPK2 enzymes, showing their broad substrate specificity and ability to selectively synthesize pyrimidine nucleoside diphosphates with high yield.

Cytoophidium complexes resonate with cell fates

The paper investigates how cytoophidium complexes formed by different metabolic enzymes relate to cell fates in yeast, showing that blocking CTPS cytoophidium assembly disrupts quiescence and affects NAD biosynthesis.

An unusual activity of mycobacterial MutT1 Nudix hydrolase domain as a protein phosphatase regulates nucleoside diphosphate kinase (NDK) function

This paper shows that mycobacterial MutT1, through its Nudix hydrolase domain, functions as a protein phosphatase to regulate NDK-Pi levels and prevent the conversion of 8-oxo-dGDP to 8-oxo-dGTP, thereby reducing A to C mutations.

Free Amino Acids Accelerate the Time-Dependent Inactivation of Rat Liver Nucleotide Pyrophosphatase / Phosphodiesterase Enpp3 elicited by EDTA

The paper investigates how free amino acids affect the EDTA-induced inactivation of rat liver NPP/PDE Enpp3 and identifies Enpp3 as a 2,3-cGAMP hydrolase.