Note: Intro -- Preface -- Contents -- 128 Activity-Based Protein Profiling-Enabling Multimodal Functional Studies of Microbial Communities -- Abstract -- 1 Introduction -- 2 Probe Design -- 2.1 Activity- and Affinity-Based Probes for Multimodal Characterization of Microbiome Function -- 2.2 Click Chemistry and Sample Analysis -- 3 Challenges of Microbiome Proteomics and How ABPP Can Facilitate -- 4 Biological Applications for ABPP -- 4.1 Host-Associated Microbial Communities -- 4.1.1 Xenobiotic Metabolism -- 4.1.2 Bile Acid Metabolism and Signaling -- 4.2 Environmental Microbial Communities -- 4.2.1 Metabolic Activity and Translation -- 4.2.2 Vitamin Metabolism -- 4.2.3 Community Signaling -- 5 Current Challenges and Outlook -- References -- 135 Activity-Based Protein Profiling Methods to Study Bacteria: The Power of Small-Molecule Electrophiles -- Abstract -- 1 Introduction -- 1.1 Activity-Based Probes: What They Are and How They Work -- 2 Probe Design Strategies -- 2.1 Reactive Warhead and Recognition Elements -- 2.2 Linker -- 2.3 Reporter -- 2.3.1 Quenched Activity-Based Probes -- 2.3.2 Bioorthogonal Ligation Reactions -- 3 Detection Methods -- 3.1 Gel-Based Detection -- 3.2 Live-Cell Imaging -- 3.3 Mass Spectrometry -- 4 ABPP in Bacteria -- 4.1 Serine-Reactive Probes -- 4.2 Cysteine-Reactive Probes -- 4.3 Antibiotic-Derived Probes -- 4.4 Carbohydrate-Based Probes -- 4.5 Probes Inspired by Natural Products -- 5 Application of ABPP in Natural Product Target Discovery -- 6 Conclusion -- References -- 125 Opportunities and Challenges in Activity-Based Protein Profiling of Mycobacteria -- Abstract -- 1 Introduction -- 2 Activity-Based Protein Profiling in Mycobacterium tuberculosis -- 2.1 Profiling of ATP-Binding Proteins -- 2.2 Profiling of Serine Hydrolase Enzymes -- 3 Development of Activity-Based Probes for Applications to Mycobacteria. , 3.1 Activity-Based Probe for the Adenylating Enzyme MbtA -- 3.2 Activity-Based Probe for the Serine Protease Hip1 -- 4 Identification of Inhibitor Targets Using ABPP in Mycobacteria -- 4.1 Targets of Tetrahydrolipstatin -- 4.2 Targets of the β-Lactone EZ210 -- 4.3 Targets of Staurosporine -- 4.4 Using Activity-Based Protein Profiling to Investigate Inhibitor Mechanism of Action -- 5 Summary and Outlook -- Acknowledgements -- References -- 129 Activity-Based Protein Profiling at the Host-Pathogen Interface -- Abstract -- 1 Introduction -- 2 Applications of ABPP to In Vitro Models of Microbial Infection -- 2.1 Detecting Host Enzymes Active in Infected Cells -- 2.2 Profiling Pathogen Adaptation to the Host Environment -- 3 Applications of ABPP to Infected Plants -- 3.1 Discovery of Pathogen-Secreted Protease Inhibitors -- 3.2 Global Profiling of Active Enzymes -- 3.3 Mechanistic Studies of Proteasome Activity and Inhibition -- 4 Applications of ABPP to Infected Animals -- 5 Applications of ABPP to Inhibitor Discovery and Characterization -- 5.1 Identifying the Targets of Bioactive Inhibitors -- 5.2 High-Throughput Screens for Selective Inhibitors -- 5.3 Rational Design and Optimization of Inhibitors -- 6 Concluding Remarks -- Acknowledgements -- References -- 126 Chemical Proteomic Profiling of Protein Fatty-Acylation in Microbial Pathogens -- Abstract -- 1 Introduction -- 2 Protein Fatty-Acylation -- 2.1 N-myristoylation -- 2.2 S-palmitoylation -- 2.3 Nε-Lys-Fatty-Acylation -- 3 Chemical Proteomic Methods for Profiling Fatty-Acylation -- 3.1 Chemical Reporter Strategy for Studying Fatty-Acylation -- 3.2 Acyl-Biotin Exchange (ABE) Strategy for Studying S-palmitoylation -- 4 Proteomic Profiling of Fatty-Acylation in Eukaryotic Pathogens -- 4.1 Proteomic Profiling of N-myristoylation in Parasites -- 4.2 Proteomic Profiling of S-palmitoylation in Parasites. , 4.3 Proteomic Profiling of N-myristoylation and S-palmitoylation in Fungal Pathogens -- 5 Protein Fatty-Acylation in Bacterial Virulence -- 5.1 Host-Mediated Fatty-Acylation of Bacterial Effectors -- 5.2 Modulation of Host Fatty-Acylation by Bacterial Effectors -- 6 Conclusions -- References -- 134 How to Target Viral and Bacterial Effector Proteins Interfering with Ubiquitin Signaling -- Abstract -- 1 Introduction -- 2 The Current Toolbox -- 2.1 DUB Targeting Covalent Probes -- 2.2 E1-E2-E3 Targeting Covalent Probes -- 2.3 Assay Reagents -- 2.4 (Poly)Ub Chains -- 3 Applications -- 3.1 Applications in Virology -- 3.2 Applications in Bacteriology -- 3.3 Legionella Effector Enzymes: The Odd-Ones Out -- 4 Conclusions -- References -- 139 ABPP and Host-Virus Interactions -- Abstract -- 1 Introduction -- 2 Viral Entry -- 3 Viral Replication -- 3.1 Role of Triglycerides -- 3.2 Role of Phosphatidylinositides -- 3.3 Role of Cholesterol -- 4 Programmed Cell Death -- 5 Viral Evasion of the Immune Response -- 5.1 Viral Alterations to Proteasome Activity -- 5.2 NFκB Signalling During Herpesvirus Infection -- 5.3 Virally Encoded Deubiquitinases -- 6 Viral Assembly and Egress -- 7 Selective Labelling of Individual Viral Enzymes -- 8 Future Objectives -- 9 Conclusions -- References -- 123 Activity-Based Protein Profiling for the Study of Parasite Biology -- Abstract -- 1 Background -- 2 Activity-Based Probes for Target Discovery in Parasites -- 2.1 Profiling Protease Activity -- 2.1.1 Cysteine Proteases -- 2.1.2 Serine Proteases -- 2.1.3 Threonine Proteases -- 2.1.4 Aspartyl and Metalloproteases -- 2.2 Profiling Acyl-Protein Thioesterases -- 2.3 Profiling Protein Kinases -- 3 Activity-Based Protein Profiling in Parasites: An Exciting Future -- References -- 124 Deciphering T Cell Immunometabolism with Activity-Based Protein Profiling -- Abstract -- 1 Introduction. , 1.1 Cellular Interactions that Regulate T Cell Responses -- 1.2 Cell Signaling in T Cell Responses -- 1.3 Cell Metabolism in T Cell Responses -- 1.4 Fate Decisions in T Cells -- 2 Features of Dysfunctional T Cells -- 2.1 Anergy/Tolerance -- 2.2 Dysfunction/Exhaustion -- 2.3 Extrinsic Regulation of T Cell Metabolism -- 2.4 New Opportunities for ABPP Discovery in T Cell Biology -- 3 Functional Insights into T Cell Biology Using ABPP Methods -- 3.1 ABPP Technology -- 3.2 ABPP Discovery of Dimethyl Fumarate Mode of Action in T Cells -- 3.3 ABPP Discovery of New Metabolic Regulators of T Cell Proliferation -- 3.4 ABPP Discovery of Proteasome Regulation of T Cell Fate -- 4 Using ABPP to Probe Immunometabolism in the Tumor Microenvironment -- 4.1 Diacylglycerol Signaling as an Intrinsic Regulator of TCR Activation -- 4.1.1 Diacylglycerol Kinase Family and Biochemistry -- 4.1.2 ABPP Discovery of Novel Druggable Sites of DGKs -- 4.1.3 ABPP Strategies for Discovery of DGK Inhibitors -- 4.2 Extrinsic Regulators of T Cell Metabolism -- 4.2.1 Metabolic Checkpoints in Glycolysis -- 4.2.2 Glutamine Dependence for Effector Function -- 4.2.3 Immunosuppression by Tryptophan Depletion -- 5 Conclusions -- References -- 137 Small-Molecule Inhibitors of PARPs: From Tools for Investigating ADP-Ribosylation to Therapeutics -- Abstract -- 1 Introduction -- 1.1 The PARP Family -- 1.2 Summary of Review -- 2 Common and Distinct Features in the Catalytic Domain of PARPs -- 2.1 The NAD+ Binding Domain -- 2.2 HYE Versus HYΦ PARPs -- 2.3 Non-Conserved Loops -- 3 Early Developments in the Field: Initial Focus on Small-Molecule Inhibitors of PARP1 -- 3.1 The Founding PARP Inhibitors -- 3.2 PARP1/2 Identified as Therapeutic Targets in Cancer -- 4 Moving Beyond PARP1/2 -- 4.1 Forward Chemical Genetic Screen Identifies a Small-Molecule Inhibitor of PARP5a/b. , 4.2 A Dearth of Selective and Potent Inhibitors for the HYΦ PARP Subfamily -- 5 Structural Studies of PARP Inhibitors: Insights into Inhibitor Potency and Selectivity -- 5.1 Structural Studies of HYE PARP Inhibitors -- 5.2 Structural Studies of HYΦ PARP Inhibitors -- 5.3 Pharmacophore for PARP Inhibitors -- 6 Chemical and Biological Reagents for Measuring PARP Activity -- 6.1 NAD+ Analogs for In Vitro Analysis -- 6.2 Detection Methods with Endogenous NAD+ -- 7 Assessing PARP Inhibitor Selectivity Across the PARP Family -- 7.1 Profiling Using Protein Stabilization Reveals Lack of Selectivity of Many PARP Inhibitors -- 7.2 Polypharmacology Among PARP Inhibitors -- 8 Conclusions and Future Directions -- References -- 132 Development of Activity-Based Proteomic Probes for Protein Citrullination -- Abstract -- 1 Introduction -- 2 PAD Structure and Function -- 2.1 PAD Structures -- 2.2 PAD Substrate Recognition and Catalytic Mechanism -- 3 PAD Inhibitors -- 3.1 Reversible PAD Inhibitors -- 3.2 Irreversible PAD Inhibitors -- 4 Activity-Based Proteomic Probes Targeting the PADs -- 4.1 First-Generation PAD-Targeted ABPPs -- 4.2 Second-Generation PAD-Targeted ABPPs -- 4.3 Phenylglyoxal-Based Probes to Detect Protein Citrullination -- 5 Conclusions -- References -- 138 Recent Advances in Activity-Based Protein Profiling of Proteases -- Abstract -- 1 Introduction -- 2 Influencing Selectivity -- 2.1 Non-natural Amino Acids -- 2.2 Application of Antibodies -- 2.3 Modification of Target Proteases -- 3 Detection Tags -- 3.1 Fluorophores -- 3.2 Isotopes -- 3.2.1 Stable Isotopes -- 3.2.2 Radioactive Isotopes -- 3.3 Biotin and Detection by MS -- 3.4 Dual Detection -- 4 Examples of ABPP on Specific Proteases -- 4.1 Neutrophil Serine Proteases -- 4.2 Caspases -- 4.3 Malt1 -- 4.4 The Proteasome -- 4.5 Matriptase -- 5 Conclusions & -- Future Directions. , Acknowledgements.