ArticleThe Journal of biological chemistry2015
Human γ-Glutamyl Transpeptidase 1: STRUCTURES OF THE FREE ENZYME, INHIBITOR-BOUND TETRAHEDRAL TRANSITION STATES, AND GLUTAMATE-BOUND ENZYME REVEAL NOVEL MOVEMENT WITHIN THE ACTIVE SITE DURING CATALYSIS.
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 1 of them a synthesis that pooled it.
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Who cites it
21 citing papers in PubMed, 1 synthesis or guideline pooled it, 61 citations in OpenAlex.
- From Gene to Enzyme: Multidimensional Decoding of the GGT Molecular Family and Its Clinical Tumor Diagnosis.Cancer medicine · 2025Pooled it
- Article
- Naphthalimide-Based Fluorescent Probe for Portable and Rapid Response to γ-Glutamyl Transpeptidase.Molecules (Basel, Switzerland) · 2025Article
- Review
- New Insight into the Substrate Selectivity of Bovine Milk γ-glutamyl Transferase via Structural and Molecular Dynamics Predictions.Molecules (Basel, Switzerland) · 2023Article
- Design and evaluation of novel analogs of 2-amino-4-boronobutanoic acid (ABBA) as inhibitors of human gamma-glutamyl transpeptidase.Bioorganic & medicinal chemistry · 2022Article
- Hormesis and Oxidative Distress: Pathophysiology of Reactive Oxygen Species and the Open Question of Antioxidant Modulation and Supplementation.Antioxidants (Basel, Switzerland) · 2022Review
- Article
- Fluorescent probes for visualizing ROS-associated proteins in disease.Chemical science · 2021Review
- A Systematic Review of Serum γ-Glutamyltransferase as a Prognostic Biomarker in Patients with Genitourinary Cancer.Antioxidants (Basel, Switzerland) · 2021Review
- Inhibition of γ-glutamyltransferase ameliorates ischaemia-reoxygenation tissue damage in rats with hepatic steatosis.British journal of pharmacology · 2020Article
- Probing the Interactions of Sulfur-Containing Histidine Compounds with Human Gamma-Glutamyl Transpeptidase.Marine drugs · 2019Article
- Effect of the inserted active-site-covering lid loop on the catalytic activity of a mutantRSC advances · 2019Article
- Sulfur-containing histidine compounds inhibit γ-glutamyl transpeptidase activity in human cancer cells.The Journal of biological chemistry · 2019Article
- Glutathione Metabolism in Renal Cell Carcinoma Progression and Implications for Therapies.International journal of molecular sciences · 2019Review
- Glutathione metabolism in cancer progression and treatment resistance.The Journal of cell biology · 2018Review
- Structure of 6-diazo-5-oxo-norleucine-bound human gamma-glutamyl transpeptidase 1, a novel mechanism of inactivation.Protein science : a publication of the Protein Society · 2017Article
- Tumor and serum gamma-glutamyl transpeptidase, new prognostic and molecular interpretation of an old biomarker in gastric cancer.Oncotarget · 2017Article
- High Resolution X-ray Diffraction Dataset for Bacillus licheniformis Gamma Glutamyl Transpeptidase-acivicin complex: SUMO-Tag Renders High Expression and Solubility.The protein journal · 2017Article
- "Phylogenetic and evolutionary analysis of functional divergence among Gamma glutamyl transpeptidase (GGT) subfamilies".Biology direct · 2015Article
Corrections and comments
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Authors and funding
6 authors at 4 institutions in 1 country.
Funding
Abstract
γ-Glutamyl transpeptidase 1 (GGT1) is a cell surface, N-terminal nucleophile hydrolase that cleaves glutathione and other γ-glutamyl compounds. GGT1 expression is essential in cysteine homeostasis, and its induction has been implicated in the pathology of asthma, reperfusion injury, and cancer. In this study, we report four new crystal structures of human GGT1 (hGGT1) that show conformational changes within the active site as the enzyme progresses from the free enzyme to inhibitor-bound tetrahedral transition states and finally to the glutamate-bound structure prior to the release of this final product of the reaction. The structure of the apoenzyme shows flexibility within the active site. The serine-borate-bound hGGT1 crystal structure demonstrates that serine-borate occupies the active site of the enzyme, resulting in an enzyme-inhibitor complex that replicates the enzyme's tetrahedral intermediate/transition state. The structure of GGsTop-bound hGGT1 reveals its interactions with the enzyme and why neutral phosphonate diesters are more potent inhibitors than monoanionic phosphonates. These structures are the first structures for any eukaryotic GGT that include a molecule in the active site covalently bound to the catalytic Thr-381. The glutamate-bound structure shows the conformation of the enzyme prior to release of the final product and reveals novel information regarding the displacement of the main chain atoms that form the oxyanion hole and movement of the lid loop region when the active site is occupied. These data provide new insights into the mechanism of hGGT1-catalyzed reactions and will be invaluable in the development of new classes of hGGT1 inhibitors for therapeutic use.
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