Journal:Protein Science:3

Torpedo californica acethylcholinesterase is stabilized by binding of a divalent metal ion to a novel and versatile 4D motif

Israel Silman, Valery L. Shnyrov, Yacov Ashani, Esther Roth, Anne Nicolas, Joel L Sussman, and Lev Weiner ^[1]

Molecular Tour
Metal ions are often involved in catalytic functions in proteins, but may also serve to stabilize them. Thus, Torpedo californica acetylcholinesterase (TcAChE) is strongly stabilized against thermal denaturation by the divalent cations, Mg⁺², Mn⁺², and Ca⁺². Solution of the crystal structures of the complexes of TcAChE with Mg⁺² and Ca⁺². revealed that stabilization is achieved by binding of the divalent metal ions to a cluster of carboxylate groups of four aspartates that has been called a ₄D motif. The complex contains, in addition, several water molecules, and while the metal ions bind directly to two of the Asp carboxylates, they bind to the other two indirectly, via waters.

The ₄D motif is a novel motif, which has not been described before. The ASSAM server, http://27.126.156.175/assam, which identifies structural motifs in proteins, revealed that many other proteins contain the ₄D motif, and in a substantial percentage of them solution of their crystal structures reveals one of the three metal ions referred to above, or also Zn⁺². Whereas in TcAChE the ₄D motif contains a single divalent ion, together with the waters, in some such complexes two or three metal ions are seen. The ₄D motif is thus a versatile motif with respect to the number of ions and waters that it contains.

₄D motif in TcAChE:

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The 4 Asp residues, D326, D389, D392 and D393, are shown as sticks, with carbons in green, oxygens in red, and nitrogens in blue. Solvent waters are shown as blue spheres, and the metal ions as magenta spheres, with their sizes proportionate to their Van der Waals radii; the oxygens of the uranyl moiety are shown as red spheres. Non-covalent hydrogen bonds and ionic bonds are shown as dashed white lines.

References

1. ↑ REF