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Eugene Permyakov

ISBN: 978-0-470-44774-1 August 2009 650 Pages


Synthesizes the current knowledge in the field and provides new insights into medical applications

Metalloproteomics is the large-scale study of metal-binding proteins. These proteins, which represent about one quarter of all the proteins in the Protein Data Bank, play important roles in all biological systems and all biological processes. Metalloproteomics provides the latest information on all major families of metal-binding proteins, including their structural, physico-chemical, and functional properties, enabling readers to better understand these proteins. Moreover, the book demonstrates how understanding the structures, properties, and functions of intracellular and extracellular metal-binding proteins may unlock the key to drug development for the treatment of a myriad of diseases.

Written by Eugene Permyakov, an international expert and pioneer in the structural analysis of metal-binding proteins, the book offers

  • Theoretical introduction to cation binding
  • Broad range of methods for investigating the binding of different cations to proteins

  • Characteristics of interactions of physiologically important cations of Ca, Mg, Zn, Fe, Mn, Co, Cu, Ni, Mo, W, Na, and K with proteins

  • Detailed considerations of structural and physico-chemical properties of the metal-binding proteins

  • Interactions of all other metal cations with proteins

  • Interactions of different types of cations with nucleic acids

Throughout the text, the author integrates principles of proteomics. In addition, detailed examples underscore the role metal-binding proteins play in health and medicine.

Bringing together and analyzing all the latest findings, Metalloproteomics' scope and level of insight are unparalleled. It is recommended for biophysicists, biochemists, enzymologists, cell and molecular biologists, protein and peptide scientists, organic and bioinorganic chemists, and chemical biologists.


Introduction to the Wiley Series on Protein and Peptide Science.


1 Complexes of Metal Cations and Low-Molecular-Mass Compounds and of Metal Cations and Proteins.

1.1. Biologically Significant Metal Cations.

1.2. Structures and Properties of the Complexes of Metal Cations and Low-Molecular-Mass Compounds.

1.3. Dissociation Constants for Complexes of Metal Cations and Low-Molecular-Mass Compounds.

1.4. Solubilities of Complexes of Calcium and of Some Other Metal Cations.

2 General Regularities of the Binding of Metal Cations to Proteins.

2.1. The Structures of the Protein-Binding Sites of Calcium, Magnesium, Zinc, and Transition Metal Ions.

2.2. Binding Stoichiometry and Binding (Dissociation) Constants.

2.3. Protein Families.

3 Experimental Methods Used for Studies of the Binding of Metal Cations.

3.1. Atomic Flame Absorption Spectroscopy.

3.2. Radioactivity.

3.3. Ion-Selective Electrodes.

3.4. Calcium Buffers.

3.5. Equilibrium and Flow Dialysis.

3.6. Fluorescent Dyes.

3.7. Isothermal Titration Calorimetry.

3.8. Differential Scanning Calorimetry.

3.9. Absorption Spectroscopy.

3.10. Fluorescent Spectroscopy.

3.11. Circular Dichroism and Optical Rotatory Dispersion Spectroscopy.

3.12. Mass Spectroscopy.

3.13. Extended X-ray Absorption Fine Structure Spectroscopy.

3.14. Small-Angle X-ray Scattering.

3.15. Proteolysis.

3.16. Deuterium Exchange.

3.17. Crystallography.

3.18. Nuclear Magnetic Resonance.

3.19. Electron Spin Resonance.

3.20. Mössbauer Spectroscopy.

4 Calcium, Calcium-Binding Proteins, and Their Major Families.

4.1. EF-Hand Proteins.

4.1.1. Parvalbumin.

4.1.2. Calbindin D9k, D28k, and Calretinin.

4.1.3. S100 Proteins.

4.1.4. Calmodulin.

4.1.5. Troponin C.

4.1.6. Recoverin and Other Neuronal Calcium Sensor Proteins.

4.1.7. Calcium-Regulated Photoproteins (Aequorin, Obelin).

4.1.8. Calcineurin.

4.1.9. Penta-EF-hand Family of Ca2+-Binding Proteins.

4.1.10. Sarcoplasmic Calcium-Binding Protein and Calerythrin.

4.1.11. Spectrin and α-Actinin.

4.2. Other Cytosolic Proteins That May be Calcium Modulated.

4.2.1. Annexins.

4.2.2. C2-Domain-Containing Proteins.

4.2.3. α-Lactalbumin and Calcium-Binding Lysozymes.

4.2.4. Calcium ATPases.

4.3. Extracellular Calcium-Binding Proteins.

4.3.1. Cell Matrix Proteins.

4.3.2. Cadherins.

4.3.3. Serum Amyloid P Component.

4.3.4. Integrin.

4.3.5. Blood Clotting Proteins.

4.3.6. Osteocalcin.

4.3.7. Ca2+-Binding Lectins.

4.3.8. D-Galactose–Binding Protein.

4.3.9. Calsequestrin.

4.3.10. Ca2+-Binding Hydrolytic Enzymes.

5 Interactions of Calcium-Binding Proteins with Low-Molecular-Mass Compounds, Peptides, Proteins, and Membranes.

5.1. Interactions with Low-Molecular-Mass Compounds.

5.2. Interactions with Peptides and Proteins.

5.3. Interactions with Membrane Systems.

6 Calcium-Binding Proteins in Various Systems.

6.1. Calcium-Binding Proteins in Muscles.

6.2. Calcium-Binding Proteins in Nervous System.

6.3. Participation of Calcium-Binding Proteins in Blood Coagulation Process.

6.4. Participation of Calcium-Binding Proteins in the Calcification of Hard Tissues.

6.5. Cytotoxic Activity of Calcium-Binding Proteins.

6.6. Calcium-Binding Proteins in Bacteria.

7 The Binding of Magnesium Ions to Proteins.

8 The Binding of Zinc Ions to Proteins.

8.1. Structural Zinc-Binding Sites.

8.1.1. Zinc Fingers.

8.1.2. Zinc-Binding Sites, Containing His and Asp/Glu.

8.1.3. Interwoven Zinc-Binding Sites.

8.2. Catalytic Zinc-Binding Sites.

8.2.1. Alcohol Dehydrogenase.

8.2.2. Metalloproteases.

8.2.3. Astacin Superfamily.

8.2.4. β-Lactamases.

8.2.5. Carbonic Anhydrases.

8.3. Co-Catalytic Zinc-Binding Sites.

8.3.1. Superoxide Dismutase.

8.3.2. Phosphatases.

8.3.3. Aminopeptidases.

8.4. Protein Interface Zinc-Binding Sites.

8.4.1. Protein Interface Catalytic Zinc-Binding Sites.

8.4.2. Zinc-Binding Sites in Superantigens.

8.4.3. Zinc-His/Glu Sites at Protein Interfaces.

8.4.4. Zinc-Cys Protein Interface Sites.

8.5. The Binding of Zinc Ions to Calcium-Binding Proteins.

8.6. Some General Notes on Zinc-Binding Sites.

8.7. Zinc Ions in Cells.

9 The Binding of Copper Ions to Proteins.

9.1. Multicopper Blue Proteins.

9.1.1. Nitrite Reductase.

9.1.2. Laccase.

9.1.3. Ascorbate Oxidase.

9.1.4. Tyrosinases.

9.1.5. Ceruloplasmin.

9.2. Monocopper Blue Proteins.

9.2.1. Plastocyanin.

9.2.2. Azurin.

9.3. Binuclear CuA Sites.

9.3.1. Cytochrome c Oxidase.

9.3.2. N2O-Reductase.

9.3.3. Hemocyanins.

9.4. Copper Transport and Anticopper Protection.

9.5. Interactions of Copper with Prion Proteins.

9.6. Alzheimer’s and Parkinson’s Diseases and Metal Cations.

9.7. Wilson’s Disease, Menkes Syndrome, and Copper Ions.

10 Iron-Binding Proteins.

10.1. Iron-Containing Heme Proteins.

10.1.1. Porphyrin and Heme.

10.1.2. Myoglobin.

10.1.3. Hemoglobin.

10.1.4. Cytochromes.

10.1.5. Peroxidases and Catalases.

10.2. Transferrin and Lactoferrin.

10.3. Ferritin and Bacterioferritin.

10.4. The Proteins with Fe–S Clusters.

10.4.1. Nitrogenase.

10.4.2. Hydrogenases.

10.4.3. Ferredoxins.

10.4.4. Biotin Synthase.

10.5. Bacterial Iron Homeostasis.

11 Molybdenum-Containing and Tungsten-Containing Proteins.

11.1. Xanthine Oxidase.

11.2. Sulfite Oxidase.

11.3. DMSO-Reductase.

11.4. Aldehyde : Ferredoxin Oxidoreductase and Formaldehyde : Ferredoxin Oxidoreductase.

12 Proteins Containing Nickel and Cobalt.

12.1. Urease.

12.2. Methionine Aminopeptidase.

12.3. Nitrile Hydratase.

13 Manganese-Containing Proteins.

13.1. Manganese in the Photosynthetic Systems.

13.2. Manganese-Containing Enzymes.

13.2.1. Arginase.

13.2.2. Manganese–Superoxide Dismutase.

14 Sodium-Binding and Potassium-Binding Proteins.

14.1. Potassium Channel.

14.2. Sodium Pump.

14.3. The Mammalian Naþ/Hþ Exchanger.

14.4. Na+/Ca2+ Exchanger.

14.5. Enzymes Activated by Monovalent Cations.

14.5.1. K+-Activated Type I Enzymes.

14.5.2. K+-Activated Type II Enzymes.

14.5.3. Na+-Activated Type I Enzymes.

14.5.4. Na+-Activated Type II Enzymes.

14.5.5. Na+-Activated Proteolytic Enzymes.

15 Interactions of Metal Cations with Nucleic Acids.

15.1. Interactions of Metal Cations with DNA.

15.2. Interactions of Metal Cations with RNA.

16 “Nonphysiologic” Metals.

16.1. Alkali Metals.

16.1.1. Lithium (Li).

16.1.2. Rubidium (Rb).

16.1.3. Cesium (Cs).

16.1.4. Francium (Fr).

16.2. Alkali-Earth Metals.

16.2.1. Beryllium (Be).

16.2.2. Strontium (Sr).

16.2.3. Barium (Ba).

16.2.4. Radium (Ra).

16.3. Transition Metals.

16.3.1. Scandium (Sc).

16.3.2. Yttrium (Y).

16.3.3. Lanthanum (La) and Lanthanides.

16.3.4. Actinium (Ac) and Actinides.

16.3.5. Titanium (Ti).

16.3.6. Zirconium (Zr).

16.3.7. Hafnium (Hf).

16.3.8. Vanadium (V).

16.3.9. Niobium (Nb).

16.3.10. Tantalum (Ta).

16.3.11. Chromium (Cr).

16.3.12. Technetium (Tc).

16.3.13. Rhenium (Re).

16.3.14. Ruthenium (Ru).

16.3.15. Osmium (Os).

16.3.16. Rhodium (Rh).

16.3.17. Iridium (Ir).

16.3.18. Palladium (Pd).

16.3.19. Platinum (Pt).

16.3.20. Silver (Ag).

16.3.21. Gold (Au).

16.3.22. Cadmium (Cd).

16.3.23. Mercury (Hg).

16.4. Metals and Metalloids in the Groups 13 to 16.

16.4.1. Aluminum (Al).

16.4.2. Gallium (Ga).

16.4.3. Indium (In).

16.4.4. Thallium (Tl).

16.4.5. Germanium (Ge).

16.4.6. Tin (Sn).

16.4.7. Lead (Pb).

16.4.8. Antimony (Sb).

16.4.9. Bismuth (Bi).

16.4.10. Polonium (Po).

17 Concluding Remarks.