Protein Phosphorylation in Parasites: Novel Targets for Antiparasitic Intervention -- Contents -- Foreword -- Preface -- List of Contributors -- Part One: Bioinformatics -- 1 Computational Analysis of Apicomplexan Kinomes -- Introduction -- Public Resources and Computational Methods for Annotating Apicomplexan Kinomes -- Apicomplexan Resources -- Computational Methods for Phylogenetic Analysis -- Current Classification of Apicomplexan Kinomes -- Classification of the PK Superfamily -- Overview of Apicomplexan Kinomes -- An Abridged Description of Apicomplexan PK Groups -- Integrative Approaches to the Therapeutic Targeting of Apicomplexan Kinases -- Integration of Sequence and Structural Data -- Integration of Functional and Phosphoproteomic Data -- Conclusions and Future Perspectives -- List of Abbreviations -- Acknowledgments -- References -- 2 Phosphatomes of Unicellular Eukaryotic Parasites -- Introduction -- Protein Ser/Thr Phosphatases (PSPs) -- Protein Tyr Phosphatases (PTPs) -- Kinetoplastids -- Phosphatome Composition -- Functions of Protein Phosphatases -- Apicomplexans -- Phosphatome Composition -- Functions of Protein Phosphatases -- Entamoeba histolytica -- Phosphatome Composition -- Functions of Protein Phosphatases in E. histolytica -- Trichomonas vaginalis -- Giardia lamblia -- Encephalitozoon cuniculi -- Conclusions -- References -- Part Two: Functional Analysis of Parasite Kinomes and Phosphatomes -- 3 Trypanosomatid Phosphoproteomics -- Introduction -- Phosphoproteomic Techniques -- Phosphoproteomics Workflow -- Caveats and Limitations -- Quantitative Phosphoproteomics -- Trypanosomatid Phosphoproteomic Studies -- Leishmania donovani Phosphoproteomics -- Trypanosoma brucei Phosphoproteomics -- Trypanosoma cruzi Phosphoproteomics -- Trends in the Trypanosome Phosphoproteomes -- Phosphoproteomics in Antiparasitic Drug Discovery.

Future Directions -- Elucidating Trypanosome Signaling Pathways -- Technological Advances -- Conclusions -- References -- 4 Trypanosomatid Cell Division Kinases -- Introduction -- Cell Division Cycles in Trypanosomatids -- Cyclin-Dependent Kinases -- CRK3 -- Other CRKs -- NDR Kinases -- Aurora Kinase, Polo-Like Kinase, and Tousled-Like Kinase -- Aurora Kinases -- Tousled-Like Kinases -- Polo-Like Kinases -- Phosphatidylinositol Kinases -- Conclusions -- Acknowledgments -- References -- 5 Kinetoplastid AGC Kinases -- Introduction -- 3-Phosphoinositide-Dependent Kinase-1 (PDK-1) -- Cyclic Nucleotide-Dependent Protein Kinases: Protein Kinase A (PKA), Protein Kinase G (PKG) -- Protein Kinase B (PKB/Akt/RAC) -- Zinc Finger Kinase (ZFK) -- NDR Kinases -- RSK Kinases -- PKC-Like Kinase Activity -- Conclusions -- References -- 6 Plasmodium eIF2α Kinases -- Introduction -- PfeIK1 -- PfeIK2 -- PfPK4 -- Concluding Remarks -- References -- 7 Protein Kinases of the Parasitic Protist Entamoeba histolytica -- Entamoeba histolytica and Amebiasis -- Pathogenesis: Role of Signaling Pathways -- The Kinome of E. histolytica -- Serine/Threonine Kinases -- Homologs of Calcium/Calmodulin-Dependent Protein Kinases -- CMGC Group -- Cyclin-Dependent Kinases (CDKs) -- Homologs of MAPKs of E. histolytica -- Casein Kinase and Glycogen Synthase Kinase -- p21-Activated Kinases (PAKs) -- AGC Group -- Tyrosine Kinases -- Receptor Kinases -- Unclassified Protein Kinases (UPKs) -- Phosphatases -- Concluding Remarks -- References -- 8 Protein Phosphatases in Trypanosome Growth and Development -- Introduction -- Trypanosomatids -- Protein Phosphatases -- Bioinformatic Analysis of the Trypanosomatid Genomes and Proteomes -- Experimentally Characterized Trypanosomatid Protein Phosphatases -- Serine/Threonine-Specific Phosphatases -- DxDxT/V Phosphatases.

Protein Tyrosine Phosphatases (PTPs) -- Regulation of Differentiation via a Unique Protein Phosphatase Signaling Pathway in T. brucei -- The Potential of Protein Phosphatases as Drug Targets in Kinetoplastid Parasites -- Conclusions -- References -- Part Three: Role of Host Cell Kinomes and Phosphatomes in Parasitic Infections -- 9 Hijacking of Host Cell Signaling by Theileria -- Introduction -- Theileria-Induced Resistance to Apoptosis -- Hijacking of IKK Signalosomes by Theileria -- Functional CK2 is Required for Maintaining Theileria-Induced Transformation -- Mitogen-Activated Protein Kinases (MAPKs): The Activation of JNK -- JAK2 Kinase -- A PKA-Dependent Survival Pathway -- Increased Proliferation -- Phosphatidylinositol-3-Kinase (PI3-K) -- Akt/PKB -- Src Family Kinase, Hck -- Increased Metastatic Potential -- Src Family Kinases -- Rho Kinase (ROCK) -- JNK Activation Contributes to Metastatic Potential -- Persisting Within a Dividing Cell -- Hijacking of Host Cell Plk1 -- Conclusions -- References -- 10 The Role of Host- and Parasite-Encoded Kinases in Toxoplasma-Host Interactions -- Introduction -- T. gondii Invasion -- Role of Host Kinases During Parasite Growth -- T. gondii Egress -- Bradyzoite Development -- Virulence -- Conclusions -- Acknowledgments -- References -- 11 Macrophage Kinases in Leishmaniasis -- Introduction -- Macrophages Express Receptors for Leishmania Ligands -- Modulation of Macrophage CD40 Signaling by Leishmania -- Extracellular Signal-Regulated Kinase-1/2 (ERK-1/2) is Crucial in L. major Infection -- Signaling Intermediates are the Kinetic Proofreaders of Receptor Signaling -- Phosphatases Regulate Kinase-Mediated Signaling in Leishmania- Infected Macrophages -- Architecture of the Kinase Network in Macrophages -- Conclusions -- References -- Part Four: Drug Discovery.

12 Selective Inhibition of Parasite Protein Kinases -- Introduction -- Inhibition of Parasite Protein Kinases -- Interaction of Protein Kinases with ATP -- Different Mechanisms of Kinase Inhibition -- Process and Methods for Finding, Designing, and Characterizing Selective Antiparasitic Kinase Inhibitors -- Parasite Kinases as Drug Targets -- Progress in the Study of Parasite Kinases -- Parasite-Specific Protein Kinases -- Structural Parasitology -- Case Studies -- Case Study #1: Plasmodium Protein Kinase 5 (PfPK5) -- Case Study #2: and Cryptosporidium CDPK1 -- Case Study #3: Plasmodium CDPKs with Small Gatekeepers -- Case Study #4: Type 2 Inhibitors -- Conclusions -- References -- 13 Kinase Inhibitors Among Hits from Malaria Cellular Screens -- Protein and Lipid Kinase Inhibitors in TCAMS -- Kinase Inhibitor Chemical Scaffolds -- Comparison of Human and Malaria Druggable Kinomes -- Assigning Compounds to Specific Kinases -- Lipid Kinases -- Experimental Target Deconvolution for Phenotypic Hits -- Affinity Methods -- Biochemical and Microbiological Methods -- Metabolomics -- Genetics -- References -- 14 Calcium-Dependent Protein Kinases of Apicomplexan Parasites as Drug Targets -- Apicomplexa -- Drug Targets and Structure-Guided Drug Design -- Apicomplexa-Specific Drug Targets -- Apicomplexa Calcium-Dependent Protein Kinases -- Toxoplasma gondii Calcium-Dependent Protein Kinases -- Kinase Inhibitor Selectivity and Apicomplexan CDPK -- Kinase Inhibitors and the Gatekeeper Residue -- CDPKs from T. gondii, N. caninum, and C. parvum Contain Glycine at the Gatekeeper Position -- Pyrazolopyrimidine-Based TgCDPK1 Inhibitors and Drug Selectivity -- The Broader Relevance of CDPKs As a Drug Target -- Acknowledgments -- References -- 15 Protein Kinases as Suitable Targets for Combating Eimeria spp. -- Eimeria spp. the Causative Agent of Coccidiosis of Poultry.

cGMP-Dependent Protein Kinases -- PKG Inhibitors -- Cyclin-Dependent Kinases (CDK)s -- Cyclins -- Conclusions -- Acknowledgments -- References -- 16 Receptor Tyrosine Kinase Signaling and Drug Targeting in Schistosomes -- Schistosomiasis and Its Control -- Tyrosine Kinase Signaling Pathways -- Receptor Tyrosine Kinases and Signaling in S. mansoni -- SER -- SmIR-1 and SmIR-2 -- VKRs -- CTKs -- Tyrosine Kinase Drug Targeting in Schistosomes -- Conclusions -- References -- 17 Protein Kinases as Drug Targets in the Treatment of Alveolar Echinococcosis -- Introduction -- The E. multilocularis Life Cycle -- AE and Current Antiparasitic Chemotherapy -- In Vitro Cultivation Systems and Drug Screening -- Rationale for Targeting Protein Kinases -- Genomics, Transcriptomics, and the Echinococcus Kinome -- E. multilocularis Receptor Kinases -- Cellular Echinococcus Kinases as Drug Targets -- What Next? -- Conclusions -- Acknowledgments -- References -- 18 Collaborative Drug Design of Plasmodium Kinase Inhibitors -- Introduction -- Collaboration Pool and SAM Pilot Goals -- SAM Drug Design Pilot Activities -- Deployment of Service Infrastructure -- SAM Drug Design Storyboard -- Discussion and Conclusions -- References -- Index.