Biochemical and Molecular Research

Functional analysis of PRPS1 disease alleles reveals altered polymerization and cytoskeletal organization

The paper investigates how PRPS1 disease alleles affect polymerization and cytoskeletal organization in yeast and human cells, linking these changes to metabolic state and phenotypic overlap.

Structural insights into DHODH-mediated catalysis and drug resistance

This study provides structural insights into DHODH catalysis and drug resistance by analyzing conformational changes and resistance mutations.

A new conditional mouse model for Cre-mediated restoration of Hprt1 expression during brain development

This paper introduces a conditional Hprt1 mouse model to study the effects of gene restoration during brain development and demonstrates its utility in understanding reversibility in genetic disorders.

Physiological folate levels constrain nucleotide synthesis and increase dependence on nucleotide salvage

This study shows that physiological folate levels limit nucleotide synthesis in leukemia cells, making them reliant on salvage pathways for proliferation.

Deoxyribonucleotide dephosphorylation by VENOSA4 supports organellar genome replication in plants

This study shows that VEN4 dephosphorylates dNTPs to dNs, which are then used by mitochondria and chloroplasts for DNA replication in Arabidopsis.

Paralogous guanine deaminases acquired from bacteria by horizontal gene transfer promote purine homeostasis in Caenorhabditis elegans

This study identifies two paralogous guanine deaminases in C. elegans that regulate purine homeostasis, with one acquired via horizontal gene transfer from bacteria.

Nuclear adenosine metabolism defines a metabolic vulnerability unmasked by TP53 loss

The paper identifies a metabolic vulnerability in TP53-deficient cells linked to nuclear adenosine metabolism and histone methylation, showing its role in DNA damage response and tumor growth.

HSPB8 regulates CTP synthase filaments to couple nucleotide metabolism and autophagy in tumors

This study identifies HSPB8's role in regulating CTP synthase filaments to link nucleotide metabolism and autophagy in tumors, showing that disrupting these filaments impairs tumor growth and correlates with poor patient survival.

Deciphering the nucleotide driven kinetic and oligomeric dynamics in IMPDH regulation

The paper characterizes the regulatory mechanism of class II bacterial IMPDH from Burkholderia thailandensis, showing MgGTP's dual role in enzyme activity and oligomerization.

Dihydropyrimidines sustain aggressive cancer states by stabilizing DPYSL2

This study identifies dihydropyrimidines (DHPs) as signaling metabolites that sustain aggressive cancer states by stabilizing DPYSL2, linking metabolic activity to oncogenic signaling.

Deciphering AMP deaminase-2 structure, activators and regulators underpinning cellular function in human fructose and nucleotide metabolism

This study characterizes the structure and regulation of hAMPD2-2, revealing ATP activation, GTP inhibition, and Pi's role in modulating the enzyme under physiological and fructose conditions.

Van der Waals interactions mediate the enantiomeric substrate preference of the CTP:phosphoglycerate cytidylyltransferase CpgD

This study presents five high-resolution structures of CpgD, revealing van der Waals interactions mediate its enantiomeric substrate preference for 2-phospho-D-glycerate.

Position of de novo purine biosynthesis gene disruptions shapes purine-starvation phenotypes in Saccharomyces cerevisiae

The paper investigates how disruptions at different positions in the de novo purine biosynthesis pathway in yeast affect cellular responses to purine starvation.

Metabolic glues as a means of purine sensing and chemotherapeutic response

This study identifies purine nucleotides as molecular glues that regulate purine biosynthesis by tethering PPAT to NUDT5, and shows how thiopurine drugs function as metabolic glues with enhanced potency.

Quinolinic acid phosphoribosyl transferase moonlights as an apoptosis regulator to empower lung cancer progression

This study identifies QPRT as a non-canonical apoptosis regulator in NSCLC that suppresses caspase-3 activation, independent of its role in NAD biosynthesis, suggesting it as a therapeutic target.

Midgestation metabolic constraint in purine metabolism drives distinct strategies for placenta and fetal growth

The paper shows that midgestational metabolic constraints in purine metabolism drive distinct strategies for placenta and fetal growth in mice and humans.

Reinke crystals are immunoreactive for purine-synthesizing metabolic enzymes

This study identifies IMPDH and PRPS as key enzymes immunoreactive to Reinke crystals in Leydig cells, linking their formation to purine metabolism and potential therapeutic implications.

hENT Inhibition Prevents Pyrimidine-Driven Resistance to DHODH Inhibition in Malignant Rhabdoid Tumors

This study shows that hENT inhibition overcomes pyrimidine-driven resistance to DHODH inhibition in SWI/SNF-deficient pediatric cancers.

Inosine misincorporation into mRNA triggers the integrated stress response and activates an innate immune gene expression signature

This study shows that inosine misincorporation into mRNA activates the integrated stress response and an innate immune gene expression signature, linking ITPase deficiency to cellular stress.

Coordinate Up-regulation of Both TK1 and TS Expression in Cycling Cells: Mechanistic Basis and Implications for Dual-Targeted Cancer Therapy

The paper identifies coordinate up-regulation of TK1 and TS in cycling cells and shows it is essential for dTTP supply, supporting dual-targeted cancer therapy.

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.

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.

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.

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.

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.

CTP Drives Human CTPS1 Filamentation

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