ArticleACS medicinal chemistry letters2019
High-Resolution Crystal Structure of Endoplasmic Reticulum Aminopeptidase 1 with Bound Phosphinic Transition-State Analogue Inhibitor.
Article in ACS medicinal chemistry letters, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
What it found
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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
25 citing papers in PubMed, 41 citations in OpenAlex.
- Review
- The impact of ERAP1 inhibition on metabolite homeostasis of melanoma cells.Scientific reports · 2026Article
- Methods and Guidelines for Analyzing the Conformational Dynamics of Proteins in the Antigen Presentation Pathway.Methods in molecular biology (Clifton, N.J.) · 2026Article
- Quantum Mechanics/Molecular Mechanics Simulations Distinguish Insulin-Regulated Aminopeptidase Substrate (Oxytocin) and Inhibitor (Angiotensin IV) and Reveal Determinants of Activity and Inhibition.Journal of chemical information and modeling · 2025Article
- Discovery of Novel Allosteric Inhibitor Hits for Insulin-Regulated Aminopeptidase Provides Insights on Enzymatic Mechanism.ACS omega · 2025Article
- ERAP Inhibitors in Autoimmunity and Immuno-Oncology: Medicinal Chemistry Insights.Journal of medicinal chemistry · 2024Review
- Precisely modulating the chromatin trackerChemical science · 2024Article
- Structure-guided discovery of aminopeptidase ERAP1 variants capable of processing antigens with novel PC anchor specificities.Immunology · 2024Article
- Polymorphic positions 349 and 725 of the autoimmunity-protective allotype 10 of ER aminopeptidase 1 are key in determining its unique enzymatic properties.Frontiers in immunology · 2024Article
- Review
- Phosphinic Peptides as Tool Compounds for the Study of Pharmacologically Relevant Zn-Metalloproteases.ACS pharmacology & translational science · 2022Review
- Phenylsulfamoyl Benzoic Acid Inhibitor of ERAP2 with a Novel Mode of Inhibition.ACS chemical biology · 2022Article
- Inhibitor-Dependent Usage of the S1' Specificity Pocket of ER Aminopeptidase 2.ACS medicinal chemistry letters · 2022Article
- Can ERAP1 and ERAP2 Form Functional Heterodimers? A Structural Dynamics Investigation.Frontiers in immunology · 2022Article
- Conformational dynamics linked to domain closure and substrate binding explain the ERAP1 allosteric regulation mechanism.Nature communications · 2021Article
- The ERAP1 active site cannot productively access the N-terminus of antigenic peptide precursors stably bound onto MHC class I.Scientific reports · 2021Article
- ERAP1 binds peptide C-termini of different sequences and/or lengths by a common recognition mechanism.Immunobiology · 2021Article
- Discovery of Selective Inhibitor Leads by Targeting an Allosteric Site in Insulin-Regulated Aminopeptidase.Pharmaceuticals (Basel, Switzerland) · 2021Article
- Investigating the phosphinic acid tripeptide mimetic DG013A as a tool compound inhibitor of the M1-aminopeptidase ERAP1.Bioorganic & medicinal chemistry letters · 2021Article
- A systematic re-examination of processing of MHCI-bound antigenic peptide precursors by endoplasmic reticulum aminopeptidase 1.The Journal of biological chemistry · 2020Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Endoplasmic reticulum aminopeptidase 1 (ERAP1) is an intracellular enzyme that helps generate peptides presented by Major Histocompatibility Complex Class I (MHC class I) molecules and is an emerging target for immunotherapy applications. Despite almost two decades of research on ERAP1, lack of high-resolution crystal structures has hampered drug-development efforts. By optimizing the protein construct, we obtained a high-resolution (1.60 Å) crystal structure of the closed-conformation of ERAP1 with a potent phosphinic pseudopeptide inhibitor bound in its active site. The structure provides key insight on the mechanism of inhibition as well as selectivity toward homologous enzymes and allows detailed mapping of the internal cavity of the enzyme that accommodates peptide-substrates. Bis-tris propane and malic acid molecules, found bound in pockets in the internal cavity, reveal potential druggable secondary binding sites. The ability to obtain high-resolution crystal structures of ERAP1 removes a major bottleneck in the development of compounds that regulate its activity and will greatly accelerate drug-discovery efforts.
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Registered trials
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.