Ligand binding glutamic acids

The dinuclear active site of urease (1) has been studied in great detail23-29 and has inspired manifold model studies—hence a separate section, Section 6.3.4.12.7, is dedicated to the coordination chemistry related to urease. E. coli Glx I is the first example of a Ni-dependent isomerase and contains a single Ni11 ion coordinated by two histidines, two axial carboxylates of glutamic acid, and two water molecules (2).30-32 It is not active with Zn bound, which is believed to result from the inability of the Zn-substituted enzyme to bind a second aqua ligand and to adopt a six-coordinate structure. 

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. 

In conclusion, troponin binds Ca2+ in six-fold coordination and all oxygen ligands are provided from amino acids. No water is needed for the coordination complex. Aspartic acid and glutamic acid occupy key positions in the four calcium binding regions of the molecule. Transfer of calcium to tropomyosin and the actin filament during contraction is achieved by coordination changes. 

The active sites of ACE contain the sequence His-Glu-X-X-His, in which the histidines are considered to participate in Zn2+ binding and Glu in the catalytic mechanism. A third Zn2+ ligand is proposed to be a glutamic acid, and the fourth is the nucleophilic water molecule (62). This structural motif is present in a number of metallopeptidases,... 

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