Luigi F. Di Costanzo is a structural chemist and biochemist specializing in structural biology, enzymology, and protein science, with a focus on metalloenzymes and structure-based approaches to enzyme function and inhibition. He earned his Ph.D. in Chemistry from the Università degli Studi di Trieste (Italy) and completed postdoctoral training at the University of Pennsylvania, where he contributed to foundational studies on enzyme structure and inhibitor design.His research centers on the three-dimensional structure and mechanism of enzymes, with extensive experience in macromolecular crystallography, including structure determination, refinement, and analysis of protein–ligand complexes. His work integrates structural, biochemical, and biophysical approaches to understand enzyme function and guide therapeutic targeting.In addition to his research, he served for over a decade as a biocurator with the Worldwide Protein Data Bank (wwPDB) at the RCSB PDB (Rutgers University), contributing to the validation and annotation of more than 7,500 macromolecular structures. This work supported the integrity and reproducibility of structural biology data used by the global scientific community, including structural datasets that have contributed to the development of machine learning approaches to protein structure prediction, such as AlphaFold.His broader expertise includes multiscale structural characterization through complementary imaging and analytical techniques, including X-ray micro–computed tomography (µCT), linking atomic-level structure to complex biological systems, as well as contributions to community data resources, including the Protein Design Archive. As editor of the Methods in Enzymology volume “Arginase: Structure, Function, and Therapeutic Targeting,” he brings together structural, metabolic, and translational perspectives to advance the field.

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• Section I: Molecular and Structural Approaches to Arginase Function and InhibitionChapter 1: Expression, Purification, and Structural Characterization of Human and Leishmania Arginase E. D'Antonio, L.F. Di Costanzo, D.W. ChristiansonChapter 2: Systematic Structural Analysis of Arginase and the Expanded Arginase-Fold Superfamily Using the Protein Data BankL.F. Di Costanzo, D.W. Christianson, E. D'AntonioChapter 3: Synthesis of First-Generation Arginase InhibitorsF. SodanoChapter 4: Computational and Experimental Strategies for the Discovery of Non-Boronic Arginase I InhibitorsS. Gathiaka, and L.F. Di CostanzoChapter 5: Computational and Structure-Guided Design of Arginase InhibitorsM.A. FumagalliChapter 6: Metal Substitution in Arginase: Experimental Approaches to Study Metal-Dependent CatalysisG.P. GeorgiouSection II: Advanced Therapeutic Strategies and Analytical Methods for ArginaseChapter 7: Therapeutic Arginase Formulations: PEGylation, Stability, and Advanced Delivery SystemsL. Sloan, M. RudebeckChapter 8: Dual ARG1/ARG2 Inhibition: Experimental and Structural Strategies for Inhibitor Design and OptimizationM. GrzybowskiChapter 9: Synthesis of Second and Third-Generation Arginase InhibitorsF. SodanoChapter 10: Cryo-EM Workflow and Structural Characterization of Arginase–Antibody ComplexesG. ScapinChapter 11: Development and Validation of an Electrochemical Assay for Arginase ActivityA. Miglione, L. Di Costanzo, S. CintiSection III: Clinical, Metabolic, and Translational Aspects of ArginaseChapter 12: Experimental and Structural Analysis of H. pylori Arginase in Gastric Immune EvasionA.K. SauChapter 13: Alternative Arginine Utilization Pathways in Bacteria: Identifying and Assaying Agmatinase and Agmatine Deiminase Activity J. FrenchChapter 14: Arginase Deficiency and Urea Cycle Disorders: Clinical and Metabolic ManagementN. Brunetti-PierriChapter 15: Inborn Errors of Metabolism and Arginine Pathways: Experimental and Clinical ApproachesA. SchulzeChapter 16: Arginine Metabolism and Protein Balance: Experimental Approaches in Human PhysiologyM. P. K. J. EngelenChapter 17: Arginase in Cardiovascular and Vascular Inflammatory DiseaseW. DuranteSection IV: Evolutionary and Functional Diversity of Arginase and Related EnzymesChapter 18: Catalytic Diversification of the Arginase Fold: Structural and Mechanistic Insights from DcsBY. MatobaChapter 19: Plant Arginase: Structural and Functional Roles in Nitrogen MetabolismB. Sekula