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Introduction to Metallomics Supplementary Reading:

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1 Introduction to Metallomics Supplementary Reading:
Mounicou, S.; Szpunar, J.; and Lobinski, R. Chem. Soc. Rev., 2009, 38, Prof. Arthur D. Tinoco University of Puerto Rico, Rio Piedras Campus

2 1. What is the metallome? Term coined by R.J.P. Williams (2001):
The entirety of metal and metalloid species in a biological environment (i.e. cell, tissue type). It also accounts for their quantity and localization in the biological environment.

3 1. What is the metallome? Metal-Carbohydrate Coordination Complexes
Metal-DNA and RNA Coordination Complexes Metal(loid)-Containing Biomolecules Metabolites Proteins Coordination Complexes and/or Organometallic Compounds Organic Acids Inorganic Anions Amino Acids/Peptides Transport molecules (i.e. Siderophores) Metallodrug Metabolites Coordination Complexes and/or Organometallic Compounds Transport Proteins Enzymes Metal Sensing Proteins Metallochaperones Metal Stress Proteins

4 General Metal-binding proteins
2. Metallomics A good way to define metallomics is by describing what it is NOT and that is aqueous speciation. It is not merely the identification of a metal (metalloid) species. It is the revelation of the significance of a metal species in a biological context. A study of the interactions and functional connections of metal species with genes, proteins, metabolites, and other biomolecules within organisms and ecosystems. A study that is focused on bioactive metal-based molecules Metalloproteins vs General Metal-binding proteins Metalloproteins: A protein whose function is conferred by a metal. Metal-binding proteins: Protein with general metal binding site or capable of nonspecific binding of metals.

5 2A. Why the need for this field?
Many metal-biomolecule complexes will not survive common extraction methods for isolating biomolecules Typically involve the use of denaturants and chelators like EDTA Extraction protocols suggest reconstituting enzymes with metals but no generally useful reconstitution solutions Standard analytical approaches for “omics” studies ignore the importance of metals Mass spectrometry is commonly used for these investigations but the typical ionization used is not applicable to metal species - Soft ionization is best

6 2B. Areas of Interest Biological Catalysis
Metal incorporation in enzymes based on bioavailability, redox potential, coordination chemistry preference Biogeochemistry and environmental chemistry Study metals in simple and complex organisms to understand evolutionary links such as adaptation of the organisms to the changing environment Understand how organisms sense and use metals within a specific ecosystem and how they respond to environmental pollution (metal contamination)

7 2B. Areas of Interest 3. Plant biochemistry and physiology
Understand the mobilization mechanism of low solubility metals from soil and metal uptake/transport of essentials elements - Gives insight into improved nutrition for humans Explore toxic level accumulation of metals in plants 4. Clinical Chemistry Determine metal-based diseases due to nonoptimal levels of metals or mutations in genes/proteins Detection of biomarkers Drug metabolism

8 2B. Areas of Interest 5. Nutrition and essential element supplementation Characterization of the chemical forms and bioavailability of nutrients in supplements. Biological fate

9 2C. General Approaches to Metallomics
In vivo Methods to analyze metal-containing biomolecules In vitro Methods focused on DNA and protein mutations and studying the impact this may have on the metallome In silico (bioinformatics) Methods focused on the connection between genome and protein sequences and metal binding and functionalization


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