ArticleACS chemical biology2016
Molecular Mechanism for Isoform-Selective Inhibition of Acyl Protein Thioesterases 1 and 2 (APT1 and APT2).
Article in ACS chemical biology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 69 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
69 citing papers in PubMed, 104 citations in OpenAlex.
- The role of protein palmitoylation in disease pathogenesis and therapeutic innovation.Annals of medicine · 2026Review
- Lyssavirus Nucleoprotein Induces GPAT4-Mediated CYB5R1 Depalmitoylation to Suppress Ferroptosis and Promote Viral Replication.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Dynamic S-acylation controls CMG2 maturation extracellular matrix regulation and anthrax toxin susceptibility in vivo.Nature communications · 2026Article
- Protein Palmitoylation as a Molecular Switch Linking Regulated Cell Death and Disease.Biomolecules · 2026Review
- Molecular regulation and physiological role of GOLPH3-mediated Golgi retention.Nature communications · 2026Article
- Insights into Molecular Mechanisms of Polyphenolic Compounds fromPharmaceuticals (Basel, Switzerland) · 2026Article
- From lipid modification to cell death: the diverse roles of S-palmitoylation in cell fate decisions.Cell communication and signaling : CCS · 2026Review
- A novel approach to combatMicrobiology spectrum · 2026Article
- ZDHHC-Mediated Protein S-Palmitoylation in Cancer: Epigenetic Interfaces, Structural Logic and Therapeutic Targeting.International journal of medical sciences · 2026Review
- Protein S-acylation: Pathological mechanisms and novel therapeutic targets for diabetic complications.Chinese herbal medicines · 2026Review
- Post-translational protein S-palmitoylation in renal tubular injury: mechanisms and therapeutic implications.Frontiers in cell and developmental biology · 2026Review
- The Roles of ProteinCancer communications (London, England) · 2026Review
- Recent advances in S-palmitoylation and its emerging roles in human diseases.Journal of hematology & oncology · 2025Review
- Palmitoylation: an emerging therapeutic target bridging physiology and disease.Cellular & molecular biology letters · 2025Review
- Palmitoylation in cardiovascular diseases: Molecular mechanism and therapeutic potential.International journal of cardiology. Heart & vasculature · 2025Review
- Engineered depalmitoylases enable selective manipulation of protein localization and function.Nature communications · 2025Article
- An S-acylated N-terminus and a conserved loop regulate the activity of the ABHD17 deacylase.The Journal of cell biology · 2025Article
- An enzymatic-independent function of palmitoyl hydrolase in cohesin loading onto chromosome.Nucleic acids research · 2025Article
- Review
- Attenuating ABHD17 isoforms augments thebioRxiv : the preprint server for biology · 2025Article
9 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
17 authors at 1 institution in 1 country.
Funding
Abstract
Post-translational S-palmitoylation directs the trafficking and membrane localization of hundreds of cellular proteins, often involving a coordinated palmitoylation cycle that requires both protein acyl transferases (PATs) and acyl protein thioesterases (APTs) to actively redistribute S-palmitoylated proteins toward different cellular membrane compartments. This process is necessary for the trafficking and oncogenic signaling of S-palmitoylated Ras isoforms, and potentially many peripheral membrane proteins. The depalmitoylating enzymes APT1 and APT2 are separately conserved in all vertebrates, suggesting unique functional roles for each enzyme. The recent discovery of the APT isoform-selective inhibitors ML348 and ML349 has opened new possibilities to probe the function of each enzyme, yet it remains unclear how each inhibitor achieves orthogonal inhibition. Herein, we report the high-resolution structure of human APT2 in complex with ML349 (1.64 Å), as well as the complementary structure of human APT1 bound to ML348 (1.55 Å). Although the overall peptide backbone structures are nearly identical, each inhibitor adopts a distinct conformation within each active site. In APT1, the trifluoromethyl group of ML348 is positioned above the catalytic triad, but in APT2, the sulfonyl group of ML349 forms hydrogen bonds with active site resident waters to indirectly engage the catalytic triad and oxyanion hole. Reciprocal mutagenesis and activity profiling revealed several differing residues surrounding the active site that serve as critical gatekeepers for isoform accessibility and dynamics. Structural and biochemical analysis suggests the inhibitors occupy a putative acyl-binding region, establishing the mechanism for isoform-specific inhibition, hydrolysis of acyl substrates, and structural orthogonality important for future probe development.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.