Zinc

• Zinc has two main roles in biological systems: as a Lewis Acid that can activate substrates such as water, and as a structural element in a protein that stabilizes a particular structure.
• Zinc is the 2nd most abundant trace element in humans and is required for over 100 enzymes.
• Zinc is a strong Lewis acid, is not redox active, has ready formation of low coordinate binding sites, and has accessible coordination numbers of 4, 5, 6.
• Zinc Metalloenzymes are characterized by the presence of an activated water molecule bound to Zn(II).
• The coordination sphere for zinc in Carboxypeptidase A includes one water molecule, one carboxylate ion, and one phosphate ion.
• The coordination sphere for zinc in Carbonic Anhydrase II includes one water molecule, one carboxylate ion, and one phosphate ion.
• The mechanism of CO2 hydration in Carbonic Anhydrase II involves the formation of a zinc-carbonate complex, which is then converted into a zinc-bicarbonate complex.
• The coordination sphere for zinc in Alcohol Dehydrogenase includes one water molecule, one carboxylate ion, and one phosphate ion.
• The pKa of metal free water is 15.7 but can be reduced to 10 in [Zn(H2O)6]2+ and 7 with three N-donors, allowing for facile ionization of H2O.
• Carbonic Anhydrase II (CAII) is present in red blood cells and catalyzes the reversible hydration of CO2.
• The rate determining step in Carbonic Anhydrase II is not CO2/HCO3- conversion but is rather proton shuttling under participation of amino acid side chains and water network.
• Carbonic Anhydrase II increases the rate of hydrolysis by a factor of 107.
• Carbonic Anhydrase II can also catalyze hydrolysis of esters and aldehydes.
• Carbonic Anhydrase II consists of 260 amino acid residues plus one Zn2+ ion.
• The active site of Carbonic Anhydrase II lies near the bottom of a 15 Å deep cleft.
• A zinc ion coordinated by three N atoms (histidines) with the fourth site occupied by a H2O molecule is present in the active site of Carbonic Anhydrase II.
• The catalytic zinc in liver alcohol dehydrogenase is bound to the sulfur atoms of Cys-46 and Cys-174 and a nitrogen atom of His-67.
• The coordinating amino acid residues and zinc ions in Zif268 are highlighted.
• Liver alcohol dehydrogenase comprises two 40-kilodalton single polypeptide sub-units, each of which contains two zinc ions.
• Alkaline phosphatase is most active at alkaline pH, hence the name.
• The active site of Carboxypeptidase A is a cleft on one side that contains the Zn2+ ion, which is the active site.
• The zinc ion in Carboxypeptidase A is coordinated by two N atoms (histidines) and two O atoms (glutamate), with the fifth site being H2O.
• An exchangeable water molecule occupies the fourth position on the zinc in liver alcohol dehydrogenase.
• The nicotinamide ring of NAD+ is bound close to the zinc in liver alcohol dehydrogenase.
• One zinc in liver alcohol dehydrogenase is in the catalytic site which also binds NAD+.
• Alkaline phosphatase removes 5' phosphate groups from DNA and RNA, and can also remove phosphates from nucleotides and proteins.
• Carboxypeptidase A is roughly egg-shaped with approximate dimensions 50 Å x 38 Å.
• In the oxidation of alcohol two hydrogen atoms are removed - one to the 4-position of NAD+ and the other as a proton.
• The transfer to NAD+ in alcohol dehydrogenase is generally thought to be a hydride transfer.
• Structural Zinc: Zinc Fingers are also found in Zif268, a protein containing three zinc fingers in complex with DNA.
• Structural Zinc: Zinc Fingers are found in transcription factor IIIA (TFIIIA), a protein that recognises DNA and RNA, controlling gene transcription.
• Carboxypeptidase A consists of 307 amino acid residues plus one Zn2+ ion, with a MW of ca 34,600.
• Alkaline phosphatase has an active site where Zn2+ polarises the substrate making it a better electrophile.
• The other zinc in liver alcohol dehydrogenase plays a structural role binding four cysteinate residues.
• Alcohol dehydrogenase converts alcohols to aldehydes or ketones.