Coordination compounds zinc enzymes

The Walton group has also made models for zinc enzymes but attempted to incorporate another feature common to many of them, positioning the metal ion at the bottom of a constrictive cleft. The approach has the advantage that the only competing substrates ought to be small molecules that can fit inside the cleft. In the case of a compound based on cyclohexane the zinc is bound to acetate, as a model for bicarbonate, in a manner reminiscent of the enzyme. The compound, cis,cis-l,3, 5-tris[ , -3-(2-furyl)acrylideneamino]cyclohexane, has a pocket at its base, as shown in Fig. 4.21, for those metals that prefer a tetrahedral coordination geometry [43],... 

Latent forms of MMPs can be activated by mechanisms which cause the dissociation of the intramolecular complex between a particular cysteine residue and the required zinc metal ligand (a complex that blocks the active site) [47], This occurs because the cysteine of the latent enzyme is coordinated to the active site in a particular way that blocks the MMP active site. Collectively, the activation of MMPs occurs through a process which has been termed the cysteine-switch . Activators of the MMPs include proteases (e.g. plasmin), conformational perturbants (SDS, NaSCN), heavy metals and organomercurials (e.g. Au(I) compounds, Hg(II)), oxidants (e.g. OC1-), disulfide compounds (e.g. GSSG) and sulfhydryl alkylating agents (e.g. V-ethylmaleimide) [47 and refs, therein]. 

The circular dichroic spectrum of the zinc azoenzyme in solution contains one positive and two negative ellipticity bands at 420, 335, and 510 nm, respectively (Figure 3). On removal of zinc, almost the entire visible CD spectrum is abolished. It is completely restored on the addition of one gram atom of zinc per mole of enzyme. This eflFect of zinc on both the absorption and CD spectra suggests that the red color of the enzyme in solution may be caused by the formation of a zinc-azophenol coordination complex. Closely similar color changes can be observed by adding zinc to a typical azophenol compound, tetrazolyl-N-benzyloxycar-... 

Hard electrophiles like Mg(C104)2 are used to activate abiotic systems. In the enzyme liver alcohol dehydrogenase (LAD) a considerably different catalytic apparatus is present a zinc ion coordinated to two cysteines and a histidine serves as a coordinating site for the carbonyl compound/alcoholate, as illustrated in equation (10). This zinc ion has amphoteric properties consistent with the capacity to activate the reaction in both directions without being consumed, in other words to act as a catalyst. Synthetic models of this catalytically active zinc have been shown to possess some catalytic activity in analogy to the enzyme (see Section L3.3.5.1iii). 

Finally, several other metal-substituted zinc metalloprotein derivatives have been prepared, including those of VO, Fe(II), Co(III), Pt(II), and HgCl2. Although these systems add little directly to our understanding of the relationship between structure and function of the enzymes, nonetheless they represent new bioinorganic compounds and are of interest in themselves, or can add information on the coordinating capabilities, and reactivity in general, of the residues present in the active cavity. 

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