# Next-Generation Protein–Ligand Interaction Networks: APEX as a Powerful Technology

**Authors:** José Miguel Quintero-Ferrer, Lucas Silva de Oliveira, Paula Marian Vieira Goulart, Thiago Albuquerque Souza Campos, Coralie Martin, Philippe Grellier, Izabela Marques Dourado Bastos, Sébastien Charneau

PMC · DOI: 10.3390/proteomes13030026 · 2025-06-23

## TL;DR

This paper reviews APEX, a powerful peroxidase tool for studying protein interactions in living cells with high precision.

## Contribution

The paper provides a comprehensive overview of APEX's evolution and its novel applications in mapping biological interactions.

## Key findings

- APEX enables high-resolution mapping of protein–ligand interactions in living cells.
- Genetic engineering has enhanced APEX's utility for proteomic and transcriptomic studies.
- Recent innovations in substrates expand APEX's applicability in biological research.

## Abstract

Peroxidases are essential enzymes that catalyze redox reactions, with wide-ranging biological implications. Among these, an enhanced ascorbate peroxidase (APEX) has emerged as a valuable tool for studying intricate intracellular events with spatiotemporal precision, particularly in protein–protein, protein–RNA, and protein–DNA interaction networks in living cells. This review discusses APEX’s structural and functional attributes, its evolution through genetic engineering, and its transformative applications in high-resolution mapping used for proteomic and transcriptomic studies. Furthermore, it highlights recent advancements in substrate innovation and addresses current challenges and future directions in leveraging APEX for cutting-edge biological research.

## Linked entities

- **Proteins:** APEX1 (apurinic/apyrimidinic endodeoxyribonuclease 1)

## Full-text entities

- **Genes:** SNCA (synuclein alpha) [NCBI Gene 6622] {aka NACP, PARK1, PARK4, PD1}, CAMP (cathelicidin antimicrobial peptide) [NCBI Gene 820] {aka CAP-18, CAP18, CRAMP, FALL-39, FALL39, HSD26}, CCL7 (C-C motif chemokine ligand 7) [NCBI Gene 6354] {aka FIC, MARC, MCP-3, MCP3, NC28, SCYA6}, MAPT (microtubule associated protein tau) [NCBI Gene 4137] {aka DDPAC, FTD1, FTDP-17, MAPTL, MSTD, MTBT1}, FICD (FIC domain protein adenylyltransferase) [NCBI Gene 11153] {aka HIP13, HYPE, SPG92, UNQ3041}, APP (amyloid beta precursor protein) [NCBI Gene 351] {aka AAA, ABETA, ABPP, AD1, APPI, CTFgamma}, APEX1 (apurinic/apyrimidinic endodeoxyribonuclease 1) [NCBI Gene 328] {aka APE, APE1, APEN, APEX, APX, HAP1}, APEX2 (apurinic/apyrimidinic endodeoxyribonuclease 2) [NCBI Gene 27301] {aka APE2, APEXL2, XTH2, ZGRF2}, FAS (Fas cell surface death receptor) [NCBI Gene 355] {aka ALPS1A, APO-1, APT1, CD95, FAS1, FASTM}, DHX30 (DExH-box helicase 30) [NCBI Gene 22907] {aka DDX30, NEDMIAL, RETCOR}
- **Diseases:** calcium deficiency (MESH:D002128), Lewy (MESH:D018827), injury to (MESH:D014947), Parkinson's disease (MESH:D010300), tumor (MESH:D009369), infection (MESH:D007239), Alzheimer's disease (MESH:D000544), cytotoxicity (MESH:D064420)
- **Chemicals:** Amplex  Red (MESH:C470430), glutathione (MESH:D005978), ATP (MESH:D000255), Waters (MESH:D014867), lignin (MESH:D008031), 4-thiouridine (MESH:D013891), Tyrosine (MESH:D014443), Biotin-tyramide (MESH:C111551), I (MESH:D007455), cysteine (MESH:D003545), lipids (MESH:D008055), Fe (MESH:D007501), Peptides (MESH:D010455), Hydrogen (MESH:D006859), guanosine (MESH:D006151), salicylhydroxamic acid (MESH:C005703), copper (MESH:D003300), L-ascorbate (MESH:D001205), tryptophan (MESH:D014364), Laemmli buffer (MESH:C088816), sulfoxide (MESH:C005746), biotin (MESH:D001710), 3,3'-Diaminobenzidine (MESH:D015100), glutaraldehyde (MESH:D005976), calcium (MESH:D002118), poly(A) (MESH:D011061), reactive oxygen species (MESH:D017382), auxin (MESH:D007210), formaldehyde (MESH:D005557), D-mannose (MESH:D008358), biotinylated (-), porphyrin (MESH:D011166), hydrogen peroxide (MESH:D006861), phenazine (MESH:C000598831), osmium tetroxide (MESH:D009993), disulfide (MESH:D004220), protoporphyrin IX (MESH:C028025), thioether (MESH:D013440), O (MESH:D010100), formamide (MESH:C031066), heme 6-propionate (MESH:C068841), amino acids (MESH:D000596), guaiacol (MESH:D006139), nitrogen (MESH:D009584), Heme (MESH:D006418), urea (MESH:D014508), Sulfo-NHS-LC-Biotin (MESH:C061443), phenoxyl radical (MESH:C042329), peroxide (MESH:D010545), glycan (MESH:D011134), tetraguaiacol (MESH:C430963), carbohydrates (MESH:D002241), carbon (MESH:D002244), porphyrin pi-cation radical (MESH:C028565), RHPS4 (MESH:C438609)
- **Species:** Salmonella enterica (species) [taxon 28901], Bos taurus (bovine, species) [taxon 9913], PX clade (clade) [taxon 569578], Rhodophyta (red algae, phylum) [taxon 2763], Lathyrus oleraceus (garden pea, species) [taxon 3888], C. elegans [taxon 328850], Bacteriophage sp. (species) [taxon 38018], Toxoplasma gondii (species) [taxon 5811], Drosophila melanogaster (fruit fly, species) [taxon 7227], Danio rerio (leopard danio, species) [taxon 7955], Trypanosoma brucei (species) [taxon 5691], Listeria monocytogenes (species) [taxon 1639], Glycine max (soybean, species) [taxon 3847], Caenorhabditis elegans (species) [taxon 6239], Mycobacterium tuberculosis (species) [taxon 1773], Homo sapiens (human, species) [taxon 9606], Saccharomyces cerevisiae (baker's yeast, species) [taxon 4932], Plasmodium falciparum (malaria parasite P. falciparum, species) [taxon 5833]
- **Mutations:** L242A, E112K, W41F, C32S, A134P, Trp41, K14D
- **Cell lines:** HEK293T — Homo sapiens (Human), Transformed cell line (CVCL_0063)

## Figures

9 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12286260/full.md

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Source: https://tomesphere.com/paper/PMC12286260