The Protein Reviews series serves as a publication vehicle for reviews that focus on crucial contemporary and vital aspects of protein structure, function, evolution and genetics. Volumes are published online first, prior to publication in a printed book. Chapters are selected according to their importance to the understanding of biological systems, relevance to the unravelling of issues associated with health and disease, or impact on scientific or technological advances and developments. Volume 23 presents four review chapters authored by experts in related fields.
The first chapter covers the structure and function of SNM1 family nucleases. Chapter two examines the molecular details of DNA integration by CRISPR-associated (Cas) proteins during adaptation in bacteria and archaea. The third chapter reviews the ordered motions in the nitric-oxide dioxygenase (NOD) mechanism of flavohemoglobin and assorted globins with tightly coupled reductases. Chapter four reviews structural analyses of the multicopper site of CopG support a role as a redox enzyme. This volume is intended for research scientists, clinicians, physicians and graduate students in the fields of biochemistry, cell biology, molecular biology, immunology and genetics.
Author(s): M. Zouhair Atassi
Series: Advances in Experimental Medicine and Biology, 1414
Publisher: Springer
Year: 2023
Language: English
Pages: 130
City: Cham
Preface
Contents
About the Editor
Structure and Function of SNM1 Family Nucleases
1 DNA Lesions
2 Function of SNM1 Family Proteins
2.1 Human SNM1A
2.2 Human SNM1B/Apollo
2.3 Human SNM1C/Artemis
3 Conserved Domains in the SNM1 Family
4 Structure of the Catalytic Domain
4.1 Metallo-β-Lactamase Domain and Active Site Metal Ion Binding
4.2 β-CASP Domain
4.3 DNA Binding Site
5 Non-catalytic Region of SNM1 Family
5.1 SNM1A
5.2 SNM1B/Apollo
5.3 SNM1C/Artemis
6 SNM1 Proteins as Potential Pharmaceutical Targets
7 Conclusions
References
Molecular Details of DNA Integration by CRISPR-Associated Proteins During Adaptation in Bacteria and Archaea
1 Introduction
1.1 CRISPR-Cas Systems as Adaptive Immune Systems
1.2 Classification of CRISPR-Cas Systems
1.3 CRISPR Adaptation Has a Conserved Mechanism Across the Different CRISPR Types
2 Integration in Type II-A Systems
2.1 Prespacer Acquisition Precedes Integration
2.2 Cas1-Cas2 Is the Minimal Subunit for Site-Specific Prespacer Integration
2.3 Mechanisms to Ensure Fidelity and Repair During CRISPR Adaptation
2.4 Leader-Repeat as a Motif for Site-Specific Spacer Insertion in Type II-A Systems
3 Integration in Other CRISPR Systems
4 Conclusion
References
Ordered Motions in the Nitric-Oxide Dioxygenase Mechanism of Flavohemoglobin and Assorted Globins with Tightly Coupled Reducta...
1 Introduction
2 NO Reactivity and Globin-NODs
2.1 O2 and O2-
2.2 HbO2 and MbO2
2.3 Other Oxy-Globins
2.4 The FlavoHb-NOD Enzyme
2.4.1 Troubles with the Early NOD Mechanism Proposal
2.5 Cooperativity, Allostery, and Motions in the NOD Mechanism
3 The Allosteric NOD Mechanism Model
3.1 Tunnels, Ferric O2, a Lever, and Gates
3.1.1 Step 1 Motions: O2 Enters and Traverses a Long Tunnel (LT)
3.1.2 Step 2 Motions: O2 Binds to the Ferric Heme and Displaces the Distal LeuE11
3.1.3 Step 2 Motions That Allow for Step 3: O2 Binding Opens a Short Tunnel for NO
3.1.4 Step 2 Motions That Allow for Step 4: O2 Binding Relaxes the Reductase Domain
3.1.5 Step 2 Motions: O2 Binding Expels Captured Nitrate
3.2 Proposed ET Trigger and Switching Mechanism
3.2.1 Step 5 Motions That Allow for Step 6: NO Interaction Induces a Spin Crossover in the Ferric Heme
3.2.2 Step 5 Motions: The Spin Crossover-Induced Structural Motion Throws the ET Switch ON
3.3 Electron Transfer and NO Dioxygenation
3.3.1 Step 6 Motions: Electron Tunneling from the FAD to the Heme
3.3.2 Step 7 Motions: NO and O2- Radicals Bond and an O-Atom Rearranges in the Dioxygenation
3.4 Completing the Cycle, a Reversal of Protein Movements
3.4.1 Step 7 Motions: The Dioxygenation Reaction Quakes and Flexes the Structure to the Starting Position
3.4.2 Steps 7 Motions: The CD Loop Unfurls and Tenses the Reductase Domain
3.4.3 Step 7: The Dioxygenation Reaction Causes Spin Crossover and Throws the ET Switch Off
3.4.4 Step 7 Motions: The Dioxygenation Reaction Quake Closes the ST Gate
3.4.5 Steps 7 and 8 Motions: Nitrate Dissociates and Is Captured by the Unfurled CD Loop
3.4.6 Cycle Repeats Steps 1-8
4 Solving the Paradox and Addressing Existing Puzzles and Problems
4.1 Unanswered Questions, Unexplained Phenomena, and Predictions of the Model
4.2 Globin Structures and the NOD Mechanism
5 The Allosteric NOD Mechanism and the Evolution of Globin Structures
5.1 Type 1 vs. Type 2 FlavoHbs
5.2 Single-Domain Globin-NODs
5.2.1 Vitreoscilla Hb, Campylobacter Cgb, Thermoglobin, and Hell´s Gate Globin
5.2.2 Worm Hb-NODs
5.2.3 Bacterial and Plant Truncated Hb-NODs
5.2.4 Mammalian FlavoHb-Like NODs
5.2.5 Myoglobin-Like NODs
5.2.6 Phytoglobin-NODs
5.2.7 Unusual Globins with Unknown Functions
6 Heteromeric Mammalian NODs
6.1 Problems with the NOD Mechanism for Homomeric Globins
6.2 Hb α-chain and B5OR Dock to Form ``Alpha-NOD´´
6.3 Hb β-chain and CYPOR Dock to Form ``Beta-NOD´´
6.4 Cygb and B5 Dock to Form Cygb-NOD
6.5 Ngb, B5, and B5OR Dock to Form Ngb-NOD
7 Concluding Remarks
References
Structural Analyses of the Multicopper Site of CopG Support a Role as a Redox Enzyme
1 Introduction
2 Structure Overview
2.1 Copper Cluster
2.2 Thioredoxin Domain
3 Metal Site Structural Comparisons
3.1 The Cu4 Site
3.2 CuG Cluster Comparisons
3.2.1 Electron Transfer Sites
3.2.2 The CuA Site
3.2.3 The TNC Site of the Multicopper Oxidases
3.2.4 Iron-Sulfur Clusters
4 Proposed Mechanisms
4.1 Proposed Copper Reductase Mechanism
4.2 Proposed Copper Oxidase Mechanism
5 Discussion
5.1 Features of Proposed Mechanisms
5.1.1 Reductase Activity
5.1.2 Oxidase Activity
5.2 Source of Reducing Equivalents
5.3 Cellular Role of CopG
References
Index
