First zinc

An a helix in the first zinc motif provides the specific protein-DNA interactions... 

The two zinc ions fulfill important but different functions in the DNA-binding domains. The first zinc ion is important for DNA-bindlng because it properly positions the recognition helix the last two cysteine zinc ligands are part of this helix. The second zinc ion is important for dimerization since the five-residue loop between the first two cysteine zinc ligands is the main component of the dimer interaction area. 

The first zinc-carbon cell made in 1876 by the French engineer G.-L. Leclanchd was a glass jar containing an aqueous solution of ammonium chloride into which were immersed an amalgamated zinc rod (the negative electrode) and a porous... 

The report of the first zinc compound with a Zn-Zn core elicited a number of critical comments on the structure and bonding of decamethyldizincocene, and the interpretation of the results.236,237 None of the authors of these commentaries questioned the data or their interpretation. Parkin, however, has pointed out that the formal oxidation state of +1 for zinc in this compound is merely due to the convention that metals are assigned an oxidation state of 0 when they form bonds with like atoms.237 If the conventional definition of valence, namely the capacity of atoms to form bonds to other atoms is used, then the zinc atoms in decamethyldizincocene are not monovalent, but divalent. The synthesis of a paramagnetic organozinc compound in which zinc uses only one of its two 4s electrons will remain an interesting challenge to many synthetic organometallic chemists. 

The first zinc enzyme to be discovered was carbonic anhydrase in 1940, followed by car-boxypeptidase A some 14 years later. They both represent the archetype of mono-zinc enzymes, with a central catalytically active Zn2+ atom bound to three protein ligands, and the fourth site occupied by a water molecule. Yet, despite the overall similarity of catalytic zinc sites with regard to their common tetrahedral [(XYZ)Zn2+-OH2] structure, these mononuclear zinc enzymes catalyse a wide variety of reactions, as pointed out above. The mechanism of action of the majority of zinc enzymes centres around the zinc-bound water molecule,... 

Carboxypeptidase A was the first zinc enzyme to yield a three-dimensional structure to the X-ray crystallographic method, and the structure of an enzyme-pseudosubstrate complex provided a model for a precatalytic zinc-carbonyl interaction (Lipscomb etai, 1968). Comparative studies have been performed between carboxypeptidase A and thermolysin based on the results of X-ray crystallographic experiments (Argosetai, 1978 Kesterand Matthews, 1977 Monzingoand Matthews, 1984 Matthews, 1988 Christianson and Lipscomb, 1988b). Models of peptide-metal interaction have recently been utilized in studies of metal ion participation in hydrolysis (see e.g., Schepartz and Breslow, 1987). In these examples a dipole-ion interaction is achieved by virtue of a chelate interaction involving the labile carbonyl and some other Lewis base (e.g.. 

The first zinc binding motif discovered was that of the eucaryotic transcription factor TFIIIA of Xenopus laevis which contains 9 copies of a Cys2His2-Zinc motif The structure of the binding motif is shown in Fig. 1.4. The central zinc ion serves to pack an a-hehx against a P-sheet and thereby position the a-helix. The recognition of the DNA sequence occurs via this a-helix. 

The chemistry outlined in Scheme 24 was then put into effect catalytic hydrogenation of the tris-isoxazole (302) and recyclization with triethylamine gave a tricyclic ligand which was chelated with nickel ions to give (303). Introduction of the fourth nitrogen atom was accomplished by treatment of (303) with ammonium acetate, giving (304). Treatment with cyanide removed the nickel ion which was then replaced with zinc(II) to give (305). The reasons for this transmetallation step were two-fold firstly, zinc(II) corrins, as shown by Eschenmoser, can be readily demetallated, and this fact opens up many options later in the synthesis, but secondly, and more importantly, Eschenmoser s photochemical cyclization of seco-corrins (see Section 3.07.3.4.2.3) does not proceed with nickel complexes of seco-corrins, whereas zinc(II) seco-corrins can be cyclized in almost quantitative yield... 

Despite the fact that carbonic anhydrase was the first zinc metalloenzyme identified1233 and a good deal is known of its structure, there is still controversy about the nature of the various active-site species and the detailed mechanisms of their action. In particular, the identity of the group with a pXa of 7 that is involved in the mechanism, and the stereochemistry around the zinc ion during catalysis, are still in dispute. The various mechanisms proposed assume either ionization of a histidine imidazole group (bound or not to the zinc) and nucleophilic attack on C02 by the coordinated imidazolate anion,1273,1274 or ionization of the Znn-coordinated water and nucleophilic attack on C02 by OH. 1271 Many papers on this problem have appeared recently and the extensive literature is the subject of the several review articles referred to above. 

Several investigators now find that four zinc ions are bound by the dimer but only two are necessary for activity. Lazdunski et al. (52) showed that the rate of inactivation of the enzyme by EDTA is biphasic, corresponding to two different zinc binding sites associated with enzymic activity. Phosphate decreases the rate of inhibition by EDTA in a manner corresponding to the binding of phosphate with dissociation constants of 1 X 10"e for the first zinc removal and 6 X 10 6 for the second. They propose that there are four zinc binding sites, of which the strongest and weakest are required for activity. If one site is occupied by zinc and three by Cd(II), there is 11% activity. They concluded that the two essential zinc sites are the same as measured by Cohen and Wilson (see later). 

The mechanism by which MTF-1 facilitates zinc-induction of metallothionein promoter through the MREs is not known, but several models have been proposed. First, zinc may act as a coinducer by binding to MTF-1 and creating an allosteric change, allowing MTF-1 to bind to the MREs. The model proposed for mammalian MTF-l/MRE interaction has already been proven for yeast copper metallothionein systems (Furst et al., 1988). Another possibility may be that, under normal conditions, an inhibitor binds MTF-1. When an influx of zinc occurs, MTF-1 binds the zinc, undergoes a conformational change and is released from the inhibitor. The protein would then have the ability to bind to the MREs. Finally, upon an increase in intracellular zinc concentration, a specific coactivator may bind zinc and interact with MTF-1 to maximally induce transcription. 

At first zinc reduction of daphniphylline (1) was attempted without success. Therefore, deacetyldaphniphylline (2) was converted with MsCl-pyridine into the corresponding methane sulfonate (13, mp 162-164° C31H4906NS) which has a better leaving group than an acetoxyl group in 1. This compound as a hydrochloride was readily reduced with zinc powder in MeOH to codaphniphylline (9). 

Leclanche cells are the least expensive primary batteries. The first zinc-manganese dioxide cell was developed by Georges Leclanche in 1866. He developed the primary battery with an ammonium chloride and zinc chloride electrolyte, and with a natural Mn02 and carbon (usually acetylene black) cathode inserted into a zinc can. His name is still associated with this chemistry today. The battery reactions are given in Equation 10.1. 

Place 1 mL of 6 M HC1 in each of three labeled test tubes. Add a 1-cm polished strip of magnesium to the first, zinc to the second, and copper to the third. Do all of the reactions in the three test tubes at the same time assess the rates of reaction of the three metals by the speed of evolution of H2 gas then list, in decreasing order, the rates of reaction of the metals with the acid on your Report Sheet (2). 

Apparent absorption. When apparent absorption, or the amount of zinc fed minus the amount eliminated in the feces, is used to determine bloavallabillty, two problems must be considered. First, zinc collected Includes non-absorbed dietary zinc, endogenous zinc from bile and pancreatic secretions into the small intestine, and sloughed intestinal cells, as shown in Figure 1 ( ). In addition to these sources, intestinal mixing occurs and the dietary zinc consumed on one day is eliminated over many days. Figure 2 ( ) shows the excretion pattern of one group of subjects, in which total excretion of unabsorbed took from 6 to 15 days. The fecal composites... 

While zinc can readily form four-, five-, and six-coordinate complexes, structural zinc sites in proteins have 4 protein ligands and no bound water molecule. This type of coordination is also observed in many of the Protein Interface zinc sites. The first zinc enzymes recognized to have a... 

Even if the free radical chain process shown in Scheme 17 was a coimnonly accepted mechanism, some very recent work pubhshed by Lewinski and coworkers strongly questions it. They initially reported the first zinc alkylperoxide structurally characterized by X-ray diffraction,... 

This addition-elimination reaction can be applied to the preparation of squaric acid derivatives. Thus, the treatment of 3,4-dichlorocyclobutene-l,2-dione 27 with two different zinc-copper reagents furnishes polyfunctional squaric acid derivatives like 28, provided the first zinc-copper reagent bears a secondary or tertiary alkyl group (Scheme 9-26) [56]. 

One of the most important discoveries concerning the biological role of zinc occurred in 1940 when Keilin and Mann showed that zinc is an essential compound of erythrocyte carbonic anhydrase, an enzyme cata-lytically involved in the transport of CO2 in blood (6). Following the 70-year interval between the initial recognition of a metabolic zinc deficiency and the characterization of the first zinc metalloenzyme, there was a period of about 15 years before the second zinc enzyme was identified. In 1955, Vallee and Neurath reported that carboxypeptidase A from bovine pancreas contained 1 g-atom Zn per mol of protein and was essential to the function of the enzyme (7). The presence of zinc in carbonic anhydrase and carboxypeptidase A indicated that a primary role of zinc would be to function in zinc metalloenzymes (62). However, it seemed unhkely that disrupting the activity of carboxypeptidase A or carbonic anhydrase would have profound eflFects on growth. 

It has been established that the actual anode reaction is more complicated and it takes place through the following mechanism First, zinc is oxidized and reacts with hydroxide ions OH to form a transient intermediate zinc hydroxide Zn(OH)2, and then Zn(OH)2 undergoes a dissolution process in the concentrated alkali solution to form zincate Zn(OH)4, namely. 

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