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Bioinorganic Chemistry Overview Mg Ca Zn Magnesium: • Isomerases and Lyases which process carboxylate or hydroxyl group containing molecules. It acts as a Lewis acid. • Special function in chlorophylls. • ATP must be coordinated to Mg2+ to be utilized. Calcium: • Biomineralization: Hydroxyapatite in endoskeletons, aragonite and calcite in exoskeletons. • Intracellular messenger. Consequence: no Ca2+ dependent intracellular enzymes. Zinc: • Cofactor in some hydrolases and dehydrogenases. • Structure formation: zinc fingers as transcription factors and hormone receptors. Bioinorganic Chemistry Mg Ca Zn Magnesium in enzymes Magnesium acts as a Lewis acid It can be bound itself to the enzyme, example: xylose isomerase Bioinorganic Chemistry Mg Ca Zn Magnesium in enzymes It can also be coordinated to the substrate before this is bound. Examples: isocitrate lyase, isocitrate dehydrogenase Bioinorganic Chemistry Mg Ca Zn Magnesium in enzymes ATP energized enzymatic reactions are often magnesiumcatalyzed Example: glutamine synthetase Bioinorganic Chemistry Mg Ca Zn Magnesium in chlorophylls Chlorin, λmax = 388 nm, 637 nm Chlorophylls, λmax = 420-470 nm, 640-680 nm Bioinorganic Chemistry Mg Ca Zn Zinc in enzymes • Zinc: mainly in hydrolases. • Lewis acidity > Mg2+, less oxophilic. • Can trigger redox reactions by its electron-withdrawing properties. • Typical tetrahedral binding site of Zn2+ : at least 1 His and 2 more His or Cys. • Fourth coordination site is occupied by hydroxide, water, or the substrate. • Back-bonding to the imidazole π*functions increases its acidity. • Non-protein environment: Zn2+ prefers coordination number 6. • d10 system electronic structure does not imprint a special geometry. C CO π-Orbital (p combined with p) occupied O Metal d-Orbital occupied C O C O CO π∗-Orbital (p combined with p) unoccupied d - π∗ back-bonding Bioinorganic Chemistry Mg Ca Zn Zinc in enzymes Rapid equilibration of CO2 with HCO3– : carbonic anhydrase Bioinorganic Chemistry Mg Ca Zn Zinc in enzymes Lewis acid driven redox reaction: alcohol dehydrogenase Bioinorganic Chemistry Mg Ca Zn Zinc fingers • Typical feature of transcription factor proteins • Ligand environment: tetrahedral, 2 His and 2 Cys • Bind to specific regions of DNA • Binding specificity determined by geometry: large scale interaction →“Zincless” finger can be made • Target of molecular genetic engineering Bioinorganic Chemistry Mg Ca Zn Calcium in biominerals • Calcium: most abundant metal in biological minerals • Calcite and Aragonite (CaCO3): exoskeletons • Hydroxyapatite (Ca10(PO4)6(OH)2): endoskeletons, teeth • Controlled growth and degradation of crystalline domains embedded in proteins and polysaccharids → true compound materials • Sensor organs: otoliths contain CaCO3, are part of the vestibular organ which senses gravity and acceleration Bioinorganic Chemistry Mg Ca Zn Calcium as messenger • Extracellular [Ca2+] is fairly constant around 2.45 mM • Cytosolic “free“ [Ca2+] is very low, 10-100 nM • Ca2+ is actively pumped outward and into the endoplasmic reticulum, the second mechanism is extremely developed in the sarcoplasmic reticulum, the variant of muscle cells. • [Ca2+] is increased by release mechanisms triggered from outside the cell. The resulting [Ca2+] fluctuations propagate the signal received by the extracellular receptor into the intracellular target systems. • [Ca2+] release itself increases [Ca2+] release as long as [Ca2+] is low. • In muscle and nerve cells, [Ca2+] can be increased by opening voltagedependent channels to extracellular space. Bioinorganic Chemistry Mg Ca Zn Calcium as messenger Bioinorganic Chemistry Mg Ca Zn Calcium as messenger Targets of the cytosolic Ca2+ • Proteins with the EF hand motif: Troponin C, Calmodulin, and many others. • Ca2+ causes conformational changes when bound to the EF hand. • These changes in turn cause changes in the protein properties → further signal transduction. • After binding Ca2+, Troponin releases its bonds to myosin which in turn starts contraction of skeletal or heart muscles. • Calmodulin has a similar function in smooth muscle. Bioinorganic Chemistry Mg Ca Zn Calcium as messenger Calmodulin Important functional groups in the EF hand loop: • Aspartate and glutamate • Hard ligands for the hard occupants of the site: • Mg2+ (resting state) • Ca2+ (active state)
