Glutamic acid metal activation

In Staph, aureus the accumulation of glutamic acid is activated by either manganese or magnesium, and the process can be inactivated by 8-hydroxyquinoline which appears to act by chelating the metal component. If penicillin is added to the growth medium some time before the cells are harvested, it is found to exert a progressive inhibition on the ability of the harvested cells to accumulate glutamic acid. The effect is probably a secondary one. Similar results are obtained with bacitracin. 

Figure 1.9 Examples of functionally important intrinsic metal atoms in proteins, (a) The di-iron center of the enzyme ribonucleotide reductase. Two iron atoms form a redox center that produces a free radical in a nearby tyrosine side chain. The iron atoms are bridged by a glutamic acid residue and a negatively charged oxygen atom called a p-oxo bridge. The coordination of the iron atoms is completed by histidine, aspartic acid, and glutamic acid side chains as well as water molecules, (b) The catalytically active zinc atom in the enzyme alcohol dehydrogenase. The zinc atom is coordinated to the protein by one histidine and two cysteine side chains. During catalysis zinc binds an alcohol molecule in a suitable position for hydride transfer to the coenzyme moiety, a nicotinamide, [(a) Adapted from P. Nordlund et al., Nature 345 593-598, 1990.)...

The 2.0 A electron density map of carboxypeptidase A shows three zinc-protein contacts (91). The ligands have been identified as histidine-69, glutamic acid-72 and histidine-196 (91, 101), where the numbers indicate the positions of the residues in the sequence counted from the N-terminal end. The geometry of the complex is irregular but resembles a distorted tetrahedron with an open position directed towards the active site pocket, and presumably occupied by water in the resting enzyme (91). The similarity with the tentative structure of the metal-binding site in carbonic anhydrase is striking. 

Finally, enzymes that bind metal cofactors such as Zn + and Mg + can use their properties as Lewis acids, for example, electron pair acceptors. An example is the enzyme thermolysin, whose mechanism is illustrated in Fig. 9. In this enzyme, glutamate-143 acts as an active site base to deprotonate water for attack on the amide carbonyl, which is at the same time polarized by coordination by an active site Zn + ion (6). The protonated glutamic acid then probably acts as an acidic group for the protonation of the departing amine. 

Acylation of an oxygen would also be expected to lower its ability to coordinate to a metal ion, and thus to form chelates. Results from the reduction of (5)-4,5-dihydro-5-(l -oxopropyl)furan-2(3//)-one, available in optically active form from glutamic acid, support this notion24. Thus, zinc borohydride gives the chelation-controlled other hand, excellent syn selectivity in the Felkin-Anh sense can be achieved with L-Selectride. The latter method was extended to several other substrates and was uniformly successful24. 

The two metal-binding sites, which are separated by 10 A, are designated ancillary and primary .The ancillary site, also called metal site 1, is not essential for repressor activity whereas the primary site, or metal site 2, must be filled for DNA binding. Metal site 1 is occupied in all the available structures. In the DtxR structures, Fe , Mn , Co , Zn , and Np are coordinated tetrahedrally by two histidines, one with its 8 nitrogen and the other with its e nitrogen, a glutamic acid, and a sulfate or phosphate ion (Figure Similar... 

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