ArticleThe EMBO journal2006
Structure of glutamate carboxypeptidase II, a drug target in neuronal damage and prostate cancer.
Article in The EMBO journal, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 111 papers, 2 of them syntheses that pooled it.
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Who cites it
111 citing papers in PubMed, 2 syntheses or guidelines pooled it, 289 citations in OpenAlex.
- Pooled it
- Pooled it
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- Development of Prostate-Specific Lysosome-Targeting Degraders.Journal of the American Chemical Society · 2026Article
- Paving the way for future PSMA inhibitors: insights from comparative preclinical evaluations of structure modifications.EJNMMI radiopharmacy and chemistry · 2025Article
- Innovative Peptide Therapeutics in the Pipeline: Transforming Cancer Detection and Treatment.International journal of molecular sciences · 2025Review
- Prodrugs Targeting Prostate-Specific Membrane Antigen against Prostate Cancer.Journal of medicinal chemistry · 2025Review
- Review
- PSMA-Targeting Imprinted Nanogels for Prostate Tumor Localization and Imaging.Advanced healthcare materials · 2025Article
- Influence of fasting prior toEJNMMI research · 2024Article
- Theranostics Nuclear Medicine in Prostate Cancer.Pharmaceuticals (Basel, Switzerland) · 2024Review
- Anticancer activity, DFT study, ADMET prediction, and molecular docking of novel α-sulfamidophosphonates.Molecular diversity · 2024Article
- Structural, Biochemical, and Computational Characterization of Sulfamides as Bimetallic Peptidase Inhibitors.Journal of chemical information and modeling · 2024Article
- Uncovering the essential roles of glutamate carboxypeptidase 2 orthologs in Caenorhabditis elegans.Bioscience reports · 2024Article
- Targeting glutamate carboxypeptidase II in IBD.Advances in pharmacology (San Diego, Calif.) · 2024Review
- Heterogeneity of prostate-specific membrane antigen (PSMA) and PSMA-ligand uptake detection combining autoradiography and postoperative pathology in primary prostate cancer.EJNMMI research · 2023Article
- Halogen Replacement on the Lysine Side Chain of Lys-Urea-Glu-Based PSMA Inhibitors Leads to Significant Changes in Targeting Properties.Molecular imaging and biology · 2023Article
- Proteomics analysis of human breast milk by two-dimensional polyacrylamide gel electrophoresis (2D-PAGE) coupled with mass spectrometry to assess breast cancer risk.Electrophoresis · 2023Article
51 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Membrane-bound glutamate carboxypeptidase II (GCPII) is a zinc metalloenzyme that catalyzes the hydrolysis of the neurotransmitter N-acetyl-L-aspartyl-L-glutamate (NAAG) to N-acetyl-L-aspartate and L-glutamate (which is itself a neurotransmitter). Potent and selective GCPII inhibitors have been shown to decrease brain glutamate and provide neuroprotection in preclinical models of stroke, amyotrophic lateral sclerosis, and neuropathic pain. Here, we report crystal structures of the extracellular part of GCPII in complex with both potent and weak inhibitors and with glutamate, the product of the enzyme's hydrolysis reaction, at 2.0, 2.4, and 2.2 A resolution, respectively. GCPII folds into three domains: protease-like, apical, and C-terminal. All three participate in substrate binding, with two of them directly involved in C-terminal glutamate recognition. One of the carbohydrate moieties of the enzyme is essential for homodimer formation of GCPII. The three-dimensional structures presented here reveal an induced-fit substrate-binding mode of this key enzyme and provide essential information for the design of GCPII inhibitors useful in the treatment of neuronal diseases and prostate cancer.
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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.