biochemistry papers | Gist.Science

In silico evaluation of the effects of temperature on the affinity of the SV2C ligand UCB-1A to SV2 isoforms

This study combines experimental binding assays and molecular dynamics simulations to demonstrate that the SV2C-selective ligand UCB-1A maintains stable binding at physiological temperatures due to a unique hydrogen bond involving Tyr298, whereas its binding to SV2A is significantly destabilized by heat, providing a mechanistic explanation for the ligand's temperature-independent selectivity.

Zou, R., Nag, S., Sousa, V. + 13 more2026-03-21⚗️ biochemistry

Enriched-GF: A Reproducible High-Yield Autologous Blood-Derived Growth Factor Method for Regenerative Medicine

The paper introduces "Enriched-GF," a rapid and reproducible three-hour protocol combining glass bead agitation, freeze-thaw cycling, and calcium stimulation to produce a high-yield, standardized autologous growth factor concentrate that significantly outperforms conventional platelet lysate and growth factor concentrate methods in regenerative medicine applications.

Bansal, H., Singhal, M., Bansal, A. + 7 more2026-03-21⚗️ biochemistry

Rational design of a protein-protein interaction inhibitor that activates Protein Tyrosine Phosphatase 1B.

Researchers rationally designed a cell-permeable peptide inhibitor that disrupts the interaction between oxidized PTP1B and 14-3-3ζ, thereby preventing PTP1B inactivation, enhancing its tumor-suppressive activity, and inhibiting the growth of EGFR-driven cancer cells.

Londhe, A. D., Rizzo, S., Rizvi, S. M. + 5 more2026-03-21⚗️ biochemistry

Affinity purification contaminants identified by cryo-EM and mass spectrometry

This study identifies human propionyl-coenzyme A carboxylase and the PRMT5:MEP50 complex as unexpected contaminants in affinity-purified proteins from HEK293 cells, demonstrating how cryo-EM and mass spectrometry can reveal these impurities and underscoring the critical need for high resin specificity in structural biology workflows.

Belcher, E. R., Hardwick, S. W., Maia de Oliveira, T. + 1 more2026-03-21⚗️ biochemistry

A conserved isoleucine gates the diffusion of small ligands to the active site of NiFe CO-dehydrogenase

This study demonstrates that mutating the highly conserved isoleucine 563 in the hydrophobic gas channel of NiFe CO-dehydrogenase significantly enhances O2 resistance by altering residue flexibility and cavity size, though this improvement comes with an unavoidable trade-off that also affects CO diffusion.

Opdam, L., Meneghello, M., Guendon, C. + 5 more2026-03-21⚗️ biochemistry

Library docking for Cannabinoid-2 Receptor ligands

This study demonstrates that structure-based docking of a 2.6 billion molecule library against the Cannabinoid-2 receptor successfully identified eight diverse, potent, and subtype-selective ligand families by targeting polar orthosteric residues, with experimental validation confirming the accuracy of the docking predictions and the efficacy of subsequent structure-based optimization.

Rachman, M. M., Iliopoulos-Tsoutsouvas, C., Dominic Sacco, M. + 16 more2026-03-21⚗️ biochemistry

A bifunctional H/ACA snoRNP mediates both pseudouridylation and rRNA scaffolding during ribosome assembly

This study reveals that the H/ACA snoRNP snR37 functions as a bifunctional mediator in early ribosome assembly by combining its canonical role in pseudouridylating a conserved rRNA residue with a novel scaffolding function, where it recruits specific proteins to organize pre-60S intermediates and facilitate peptidyl transferase center formation.

Hafner, J., Thoms, M., Hamze, H. + 23 more2026-03-21⚗️ biochemistry

Cooperativity in E. coli Aspartate Transcarbamoylase is Tuned by Allosteric Breathing

This study reveals that *E. coli* aspartate transcarbamoylase regulates pyrimidine biosynthesis not through discrete conformational switches, but via a dynamic "breathing" mechanism where symmetric pairs of nucleotides modulate global enzyme expansion and compression to tune cooperativity and balance cellular nucleotide pools.

Miller, R. C., Patterson, M. G., Bhatt, N. + 2 more2026-03-20⚗️ biochemistry

The role of CYP3A-CYP2E1 interactions in activation of CYP3A enzymes by chronic alcohol exposure

Chronic alcohol exposure enhances CYP3A enzyme activity in human liver not by increasing enzyme levels, but through a functional interaction with alcohol-inducible CYP2E1, a mechanism confirmed by proteomic analysis and structural modeling of the CYP2E1-CYP3A4 complex.

Davydov, D. R., Ponraj, K., Davydova, N. + 5 more2026-03-20⚗️ biochemistry

Inhomogeneous Tau polymerization, core-shell organization, and seed formation during Tau condensate aging

This study elucidates how Tau condensates mature into pathological, amyloid-like seeds through an inhomogeneous core-shell restructuring and parallel molecular alignment, while revealing that their porous interiors remain accessible for therapeutic targeting.

Franck, M., Biswas, A., Jiang, P.-L. + 13 more2026-03-20⚗️ biochemistry

Decomap-seq enables efficient and reliable retrieval of spatial transcripts

The paper introduces Decomap-seq, a novel spatial transcriptomics platform that utilizes a triple-segment double-strand protected combinatorial barcoding strategy to overcome sensitivity limitations of traditional single-stranded coupling methods, thereby enabling highly efficient and reliable transcript detection for advanced tissue analysis.

Kaiqiang, Y., Zhao, X., Wenjia, W. + 1 more2026-03-20⚗️ biochemistry

Cell cycle-coupled CK1δ turnover, autoinhibition, and activity

This study reveals that CK1δ activity and abundance are dynamically coordinated throughout the cell cycle, where free active kinase is degraded in G1, unassembled kinase is stabilized in S phase to support DNA damage signaling, and mitotic entry triggers autoinhibitory phosphorylation to preserve a kinase pool for rapid post-mitotic reactivation.

Serrano, F. E., Ruppert, B., Diernfellner, A. + 1 more2026-03-20⚗️ biochemistry

Fluorometric DNA Polymerase Activity Assay for Resource-Limited Enzyme Manufacturing

This paper presents a cost-effective, accessible fluorometric DNA polymerase activity assay optimized for resource-limited settings through isothermal operation, in-house reagent synthesis, and stakeholder-informed design to enable local enzyme quality control and reduce dependence on imported tools.

Venkatramani, A., Ahmed, I., Vora, S. + 5 more2026-03-20⚗️ biochemistry

Steric shielding of the KRAS4B hypervariable region enables isoform-specific inhibition of prenylation

This study demonstrates that a directed-evolution-designed Armadillo repeat protein (dArmRP) can specifically bind and sterically shield the unstructured hypervariable region of KRAS4B to block its prenylation and membrane localization, offering a highly selective, isoform-specific strategy to inhibit this oncogene that overcomes the limitations of targeting conserved G-domains or prenylation enzymes.

Maskos, J. N., Stark, Y., Rohner, V. L. + 5 more2026-03-20⚗️ biochemistry

Discovery of metabolites produced by reactions between central carbon metabolites and cysteine that mark inflammatory macrophages

This study identifies a novel class of sulfur-containing metabolites formed by the reaction of cysteine with central carbon intermediates that specifically mark inflammatory macrophages, revealing a previously uncharted metabolic network regulated by Slc7a11 and nitric oxide that is elevated in human inflammatory lesions.

Arp, N. L., Deng, F., Lika, J. + 9 more2026-03-20⚗️ biochemistry

A metagenomic thermostable monomeric meganuclease with novel specificity and unique palindromic 3-prime overhangs

This study presents a novel metagenomic discovery strategy that led to the identification of I-MG11, a thermostable monomeric meganuclease with unique specificity for generating palindromic 3-prime overhangs, thereby expanding the molecular biology toolbox and streamlining enzyme annotation.

Dorrazehi, G. M., Penner, M., Athanasiou, C. + 5 more2026-03-20⚗️ biochemistry

A Fragment Screen Identifies Acrylamide Covalent Inhibitors of the TEAD/YAP Protein-Protein Interaction

This study identifies acrylamide fragments that covalently bind to a conserved cysteine in the TEAD palmitate pocket, thereby inhibiting the TEAD-YAP protein-protein interaction and providing a foundation for developing allosteric covalent inhibitors of the Hippo pathway.

Bum-Erdene, K., Ghozayel, M. K., Zhang, M. J. + 2 more2026-03-20⚗️ biochemistry

Structural basis of receptor retro-translocation in peroxisomal protein import

This study utilizes cryo-electron microscopy to reveal the structural mechanisms by which the Pex2-10-12 ubiquitin ligase complex, guided by Pex8, coordinates receptor recognition, gating, and mono-ubiquitination to drive the retro-translocation and recycling of peroxisomal cargo receptors.

Dempsey, N. W. M., Wang, L., Gao, N. + 3 more2026-03-20⚗️ biochemistry

Form IF Rubiscos include highly active, specific, and small subunit-independent enzymes.

This study reveals that newly discovered Form IF Rubisco enzymes can function as highly active and specific homo-octameric complexes without their essential small subunits or chaperones, challenging the long-held view that such complexity is required for efficient carbon fixation.

Otto, F., Westedt, H., Franzeck, K. P. + 8 more2026-03-20⚗️ biochemistry

Architecture of a DNA-guided Cas12a

This study presents the cryo-EM structure of Acidaminococcus sp. Cas12a bound to a pseudo-DNA guide and RNA target, revealing the structural mechanism by which the enzyme utilizes a DNA hairpin to bridge its lobes and facilitate RNA recognition, thereby providing a blueprint for future engineering.

Ocampo, R. F., Orosco, C., Huang, B. + 3 more2026-03-20⚗️ biochemistry

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