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Metalloenzymes
From Bench to Bedside
- 1st Edition - August 30, 2023
- Editors: Claudiu T. Supuran, William Alexander Donald
- Language: English
- Paperback ISBN:9 7 8 - 0 - 1 2 - 8 2 3 9 7 4 - 2
- eBook ISBN:9 7 8 - 0 - 1 2 - 8 2 4 2 3 5 - 3
Metalloenzymes: From Bench to Bedside offers a thorough overview of metalloenzymes, spanning biochemical and structural features, pharmacology, and biotechnological applicati… Read more
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Request a sales quoteMetalloenzymes: From Bench to Bedside offers a thorough overview of metalloenzymes, spanning biochemical and structural features, pharmacology, and biotechnological applications. After a brief overview, international experts in the field discuss a wide range of magnesium, calcium, zinc, manganese, nickel, iron, copper, cadmium, molybdenum, and tungsten enzymes, along with catalytic roles within their active sites. With a uniform approach throughout, each chapter includes the structure and function of the enzyme, physiologic and pathologic roles, inhibitors and activators of the enzyme (and their design), and clinical agents or compounds applied in medicine and drug discovery. This book enables scientists across academia and industry to adopt ongoing metalloenzyme research, and continuous discovery of novel metalloenzymes, in new life science studies and clinical applications.
- Examines a range of metalloenzymes, from biochemistry to pharmacology and drug design
- Each chapter examines enzyme structure and function, physiologic and pathologic roles, inhibitors and activators, and clinical application
- Features chapter contributions from international experts in the field
Active researchers in biochemistry, molecular biology, pharmaceutical science, cellular biology, applied microbiology, and biotechnology, medical chemists, clinician scientists, Clinicians and students
- Cover image
- Title page
- Table of Contents
- Copyright
- Contributors
- Preface
- Section A: Metalloenzymes
- Chapter 1: Introduction to metalloenzymes: From bench to bedside
- Abstract
- 1: Introduction
- 2: Druggability of metalloenzymes: Challenges and opportunities
- References
- Section B: Magnesium and calcium-containing enzymes
- Chapter 2.1: DNA and RNA polymerases
- Abstract
- 1: Structure and function of the enzyme(s)
- 2: Physiologic/pathologic role
- 3: Classes of inhibitors/activators and their design
- 4: Polymerase inhibitors in clinical use or in advanced development stages
- References
- Chapter 2.2: Reverse transcriptase
- Abstract
- 1: An overview of reverse transcriptase function
- 2: Structure and function of HIV-1 reverse transcriptase
- 3: Structure and function of Ty3 retrotransposon
- 4: Structure and function of telomerase reverse transcriptase
- 5: Clinically used inhibitors
- References
- Chapter 2.3: Integrase
- Abstract
- 1: Introduction
- 2: Structure of IN
- 3: Reactions catalyzed by the IN enzyme
- 4: IN-strand transfer inhibitors (INSTIs)
- 5: First-generation INSTIs
- 6: Second-generation INSTIs
- 7: New perspectives for IN inhibition
- 8: Dual-acting inhibitors
- 9: Conclusion
- References
- Chapter 2.4: Cyclin-dependent kinase 2 (CDK2)
- Abstract
- 1: Structure and function of CDK2
- 2: Physiologic and pathologic role of CDK2
- 3: Classes of inhibitors and their design
- 4: Clinically used agents or compounds in clinical development
- References
- Chapter 2.5: Catechol-O-methyltransferase (COMT)
- Abstract
- 1: Structure and function of the catechol-O-methyltransferase (COMT) enzyme
- 2: Physiologic and pathologic roles of COMT
- 3: Inhibitors of COMT and their design
- 4: Clinically used agents or compounds in clinical development
- 5: Conclusions
- References
- Chapter 2.6: d-Alanine-d-alanine ligase
- Abstract
- 1: Introduction
- 2: Structure and function of Ddl
- 3: Ddl inhibitors
- 4: Conclusions
- References
- Chapter 2.7: Paraoxonases
- Abstract
- 1: Introduction
- 2: Structure and functions of CAs
- 3: Catalyzed reactions
- 4: PON inhibition
- 5: Physiological/pathological roles of PONs
- 6: Conclusions
- References
- Chapter 2.8: Phospholipases A2
- Abstract
- Acknowledgments
- 1: Structure and function of the PLA2 superfamily of enzymes
- 2: Physiologic and pathologic roles of PLA2 enzymes
- 3: Classes of PLA2 inhibitors and their design
- 4: Conclusions
- References
- Section C: Zinc enzymes
- Chapter 3.1: Carbonic anhydrases
- Abstract
- 1: Introduction
- 2: Catalyzed reactions, structure and functions of CAs
- 3: CA inhibition mechanisms, classes of inhibitors
- 4: CA inhibitors in clinical use
- 5: CA activators
- 6: Conclusions and future prospects
- References
- Chapter 3.2: Metallo-β-lactamases
- Abstract
- Acknowledgments
- 1: Introduction
- 2: Structure and function of metallo-β-lactamases
- 3: Physiologic and pathologic role of metallo-β-lactamases
- 4: Classes of metallo-β-lactamase inhibitors and their design
- 5: Metallo-β-lactamase inhibitors in clinical development
- 6: Conclusion
- References
- Chapter 3.3: Bacterial zinc proteases
- Abstract
- 1: Introduction
- 2: Bacterial metalloproteases
- 3: Bacterial collagenase
- 4: Pseudolysin
- 5: The neurotoxins produced by tetanus and botulinum
- 6: Anthrax toxin lethal factor
- 7: Conclusions
- References
- Chapter 3.4: Matrix metalloproteases
- Abstract
- 1: Structure and function of the enzyme(s)
- 2: Physiologic/pathologic role
- 3: Classes of inhibitors/activators and their design
- 4: Clinically used agents or compounds in clinical development
- 5: Conclusion and outlook
- References
- Chapter 3.5: A disintegrin and metalloproteinases (ADAMs) and tumor necrosis factor-alpha-converting enzyme (TACE)
- Abstract
- 1: General features of ADAMs
- 2: ADAM17
- 3: ADAM8
- 4: ADAM10
- 5: ADAM inhibitors
- 6: Conclusions
- References
- Chapter 3.6: Angiotensin-converting enzyme
- Abstract
- 1: Structure and function of angiotensin-converting enzyme (ACE)
- 2: Physiologic/pathologic roles
- 3: Classes of modulators and their design
- 4: Clinically used agents or compounds in clinical development
- Conflicts of interest
- References
- Chapter 3.7: Histidinol dehydrogenase
- Abstract
- 1: Introduction
- 2: Structure and function of the enzyme HDH
- 3: Pathologic role of histidinol dehydrogenase
- 4: Classes of inhibitors and their design
- 5: Clinically used agents or compounds in clinical development
- 6: Conclusion
- References
- Chapter 3.8: Histone deacetylases and other epigenetic targets
- Abstract
- 1: Introduction
- 2: Histone deacetylase (KDACs/KDACs)
- 3: Class I and II KDAC structures
- 4: Structure of sirtuins (Class III KDACs)
- 5: Class I and II KDACs mechanism on nucleosomal core histones
- 6: Catalytic mechanisms of sirtuins (Class III KDACs)
- 7: KDACs on nonhistone proteins
- 8: Zinc-dependent KDAC inhibitors (KDACis)
- 9: Sirtuin inhibitors
- 10: Conclusions
- References
- Chapter 3.9: CD73 (5′-Ectonucleotidase)
- Abstract
- 1: Introduction
- 2: Mammalian 5′-nucleotidases
- 3: Bacterial 5′-nucleotidases
- 4: CD73 catalytic mechanism
- 5: Inhibitors of the human CD73 (hCD73)
- 6: Inhibitors of the bacterial CD73
- 7: Conclusions
- References
- Chapter 3.10: Glyoxalase II
- Abstract
- 1: Introduction
- 2: The Glyoxalase System (GS)
- 3: Glyoxalase 2 enzymes (GLOs2)
- 4: Structural aspects of GLOs2
- 5: GLOs2 biological implications
- 6: Conclusions
- References
- Chapter 3.11: Glutamate carboxypeptidase II
- Abstract
- 1: Introduction
- 2: GCP II biological localization
- 3: GCP II structure and reaction mechanism
- 4: GCP II inhibition
- 5: GCP II and diseases
- 6: Conclusions and perspectives
- References
- Chapter 3.12: Neutral endopeptidase (neprilysin)
- Abstract
- 1: Structure and function of the enzyme
- 2: Physiologic/pathologic role
- 3: Classes of inhibitors and their design
- 4: Clinically used agents or compounds in clinical development
- References
- Section D: Other metalloenzymes
- Chapter 4.1: The role of arginase in human health and disease
- Abstract
- 1: Structure and function of the arginase isozymes
- 2: Physiologic and pathologic role associated to arginase
- 3: The development of arginase inhibitors and antibodies
- 4: Compounds and arginase formulation used in clinical development
- References
- Chapter 4.2: Methionine aminopeptidases
- Abstract
- 1: Methionine aminopeptidases
- References
- Chapter 4.3: 1-Deoxy-d-xylulose 5-phosphate reductoisomerase, the first committed enzyme in the MEP terpenoid biosynthetic pathway—Its chemical mechanism and inhibition
- Abstract
- 1: Chemical mechanism and intermediary of DXR
- 2: Substrate-binding mode
- 3: DXR catalytic cycle
- 4: DXR inhibitors
- References
- Section E: Nickel enzymes
- Chapter 5.1: Urease
- Abstract
- 1: Introduction
- 2: Structure and function
- 3: Physiological roles and involvement in diseases
- 4: Insight into the dual urease-carbonic anhydrase enzyme system in H. pylori
- 5: Urease as a diagnostic tool for H. pylori infections
- 6: Urease as pharmacological target: Design and development of inhibitors
- References
- Chapter 5.2: Methyl-coenzyme M reductase
- Abstract
- 1: Methyl-coenzyme M reductase: An important biocatalyst complex in archaea metabolism
- 2: Phylogenetic and cellular localization of MCRs
- 3: Conformations of MCR and oxidation states of the coenzyme F430 nickel atom
- 4: Coenzyme F430
- 5: The MCR isoforms
- 6: Structural features of MCRs
- 7: Posttranscriptional modifications
- 8: Catalytic mechanism of MCRs
- 9: Catalytic features of MCRs
- 10: MCR inhibitors
- 11: Conclusions
- References
- Section F: Iron enzymes (heme-containing)
- Chapter 6.1: Cyclooxygenase
- Abstract
- 1: Introduction
- 2: Structure and function of the enzyme
- 3: Physiological and pathological role
- 4: Classes of modulators
- 5: Design of inhibitors
- 6: Clinically used agents and compounds in clinical development
- References
- Chapter 6.2: Cytochrome P450 (inhibitors for the metabolism of drugs)
- Abstract
- 1: Introduction
- 2: Structure and function
- 3: Physiology and pathophysiology
- 4: Classes of inhibitors/activators and their design
- 5: Conclusion
- References
- Chapter 6.3: Aromatase
- Abstract
- 1: Introduction
- 2: Structure and function
- 3: Physiology and pathophysiology
- 4: Classes of inhibitors/activators
- 5: Clinically used agents or compounds in clinical development
- References
- Section G: Iron enzymes, non-heme containing
- Chapter 7.1: Nonheme mono- and dioxygenases
- Abstract
- 1: Introduction
- 2: Pterin-dependent monooxygenases
- 3: Ring cleaving dioxygenases
- 4: 2-Oxoglutarate-dependent dioxygenases
- 5: 4-Hydroxyphenylpyruvate dioxygenase
- 6: Crystal structures of 4-hydroxyphenylpyruvate dioxygenase
- 7: Catalytic mechanism of 4-hydroxyphenylpyruvate dioxygenase
- 8: Classes of HPPD inhibitors: Triketones, pyrazoles, and isoxazoles
- 9: Disorders associated with tyrosine metabolism
- 10: Therapeutical uses of NTBC and other human HPPD inhibitors
- References
- Chapter 7.2: Indoleamine 2,3-dioxygenase
- Abstract
- 1: Introduction
- 2: Discovery of IDO
- 3: Gene, structure and catalytic mechanism of IDO
- 4: IDO1 expression in tissues and expression regulation
- 5: Physiological functions and involvement in diseases of IDO
- 6: Tryptophan 2,3-dioxygenase (TDO) and indoleamine 2,3-dioxygenase 2 (IDO2)
- 7: IDO inhibitors
- 8: Conclusions
- References
- Section H: Copper enzymes
- Chapter 8.1: Superoxide dismutases inhibitors
- Abstract
- 1: Introduction
- 2: Structure and catalytic mechanism of SOD isoforms
- 3: The roles of SODs in human diseases
- 4: SOD inhibitors
- 5: Future perspectives
- References
- Chapter 8.2: Tyrosinase enzyme and its inhibitors: An update of the literature
- Abstract
- 1: Introduction
- 2: Structure and function of the enzyme
- 3: Physiological/pathological role
- 4: Tyrosinase as pharmacological target: design and development of inhibitors
- 5: Clinically used agents or compounds in clinical development: An update of the literature
- References
- Section I: Cadmium enzymes CAs
- Chapter 9: CDCA1, a versatile member of the ζ-class of carbonic anhydrase family
- Abstract
- 1: Introduction
- 2: Biochemical features, CO2 hydration activity and its modulation
- 3: Structural features: Overall fold, substrate binding pocket, and access route
- 4: From structure to function: ζ-CAs show CS2 hydrolase activity
- 5: Conclusions and future perspectives
- References
- Section J: Molybdenum enzymes
- Chapter 10: Molybdenum enzymes
- Abstract
- 1: Introduction
- 2: The molybdenum cofactor (Moco)
- 3: Moco enzymes
- 4: Molybdenum cofactor deficiencies (MoCD)
- References
- Section K: Tungsten-containing enzymes
- Chapter 11: Tungsten-containing enzymes
- Abstract
- 1: Introduction
- 2: Tungsten an ancestral precursor of molybdenum
- 3: Tungsten-containing enzymes
- 4: Aldehyde ferredoxin oxidoreductase (AOR)
- 5: Formaldehyde ferredoxin oxidoreductase (FOR)
- 6: Glyceraldehyde-3-phosphate ferredoxin oxidoreductase (GAPOR)
- 7: Carboxylic acid reductase (CAR)
- 8: Aldehyde dehydrogenase (ADH)
- 9: Formate dehydrogenase (FDH)
- 10: N-formylmethanofuran dehydrogenase (FMDH)
- 11: Acetylene hydratase (AH)
- 12: Tungstoenzymes and human health
- 13: Conclusion
- References
- Index
- No. of pages: 634
- Language: English
- Edition: 1
- Published: August 30, 2023
- Imprint: Academic Press
- Paperback ISBN: 9780128239742
- eBook ISBN: 9780128242353
CS
Claudiu T. Supuran
Dr. Claudiu T. Supuran received his BSc in chemistry from the Polytechnic University of Bucharest, Romania (1987) and PhD in chemistry at the same university in 1991. In 1990, he became Assistant and then Associate Professor of Chemistry at the University of Bucharest. He was Visiting Scholar at the University of Florida, Gainesville, United States, at Griffith University, Brisbane, Australia, and Visiting Professor at University of La Plata, Argentina. In 1995 he moved to the University of Florence, Italy, where he is currently Full Professor in the Department of Neuroscience, Psychology, Medicine and Child Health. His main research interests include design of enzyme inhibitors and activators, heterocyclic chemistry, chemistry of sulfonamides, sulfamates, and sulfamides, biologically active organo-element derivatives, QSAR studies, X-ray crystallography of metallo-enzymes, metal complexes with biologically active ligands (metal-based drugs), carbonic anhydrases, cyclooxygenases, serine proteases, matrix metalloproteinases, bacterial proteases, and amino acid derivatives among others. He has published more than 1900 papers in these fields.
Affiliations and expertise
Full Professor, University of Florence, Neuroscience, Psychology, Medicine and Child Health, Florence, ItalyWD
William Alexander Donald
Dr. William Alexander Donald is an academic and research group leader in the School of Chemistry at the University of New South Wales, Australia. His research interests include carbonic anhydrases, coordination chemistry, and the development of bioanalytical methodologies for improving drug discovery and development. He has published more than 120 papers in these fields.
Affiliations and expertise
Associate Professor, School of Chemistry, University of New South Wales, Sydney, AustraliaRead Metalloenzymes on ScienceDirect