Journal:Protein Science:3
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Metal ions are often involved in catalytic functions in proteins, but may also serve to stabilize them. Thus, ''Torpedo californica'' acetylcholinesterase (''Tc''AChE) is strongly stabilized against thermal denaturation by the divalent cations, Mg<sup>+2</sup>, Mn<sup>+2</sup>, and Ca<sup>+2</sup>. Solution of the crystal structures of the complexes of ''Tc''AChE with Mg<sup>+2</sup> and Ca<sup>+2</sup>. 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 <sub>4</sub>D 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. | Metal ions are often involved in catalytic functions in proteins, but may also serve to stabilize them. Thus, ''Torpedo californica'' acetylcholinesterase (''Tc''AChE) is strongly stabilized against thermal denaturation by the divalent cations, Mg<sup>+2</sup>, Mn<sup>+2</sup>, and Ca<sup>+2</sup>. Solution of the crystal structures of the complexes of ''Tc''AChE with Mg<sup>+2</sup> and Ca<sup>+2</sup>. 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 <sub>4</sub>D 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 | + | 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<sup>+2</sup>. Whereas in ''Tc''AChE 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 ''Tc''AChE: | |
*<scene name='87/876867/Cv1/14'>Apo TcAChE</scene>. | *<scene name='87/876867/Cv1/14'>Apo TcAChE</scene>. | ||
*<scene name='87/876867/Cv1/15'>Mg+2/TcAChE</scene>. | *<scene name='87/876867/Cv1/15'>Mg+2/TcAChE</scene>. | ||
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[[Image:Fig_07.jpg|thumb|400px|left|'''Fig. 7.''' Sequence alignments of residues 320-400 in several AChEs and in hBChE. The numbering used is that of ''Tc''AChE. Fully conserved residues are in white on a red background. The columns for the four residues corresponding to the <sub>4</sub>D motif in ''Tc''AChE and zebrafish acetylcholinesterase are framed in green, and it can be seen that the motif is conserved only in these three AChEs. ''Tc''AChE, ''Torpedo californica'' AChE; ''Tm''AChE, ''Torpedo marmorata'' AChE; ''Ee''AChE, ''Electrophorus electricus'' AChE; ''Dr''AChE, ''Danio rerio'' AChE; ''Bf''AChE, ''Bungarus fasciatus'' AChE; HuAChE, human AChE; BoAChE, bovine AChE; MoAChE, mouse AChE; HdAChE, designed HuAChE, D4 variant<ref name="Goldenzweig">PMID:27425410</ref>; HuBChE, human BChE; ''Ag''AChE, ''Anopheles gambiae'' AChE; ''Dm''AChE, ''Drosophila melanogaster'' AChE.]] | [[Image:Fig_07.jpg|thumb|400px|left|'''Fig. 7.''' Sequence alignments of residues 320-400 in several AChEs and in hBChE. The numbering used is that of ''Tc''AChE. Fully conserved residues are in white on a red background. The columns for the four residues corresponding to the <sub>4</sub>D motif in ''Tc''AChE and zebrafish acetylcholinesterase are framed in green, and it can be seen that the motif is conserved only in these three AChEs. ''Tc''AChE, ''Torpedo californica'' AChE; ''Tm''AChE, ''Torpedo marmorata'' AChE; ''Ee''AChE, ''Electrophorus electricus'' AChE; ''Dr''AChE, ''Danio rerio'' AChE; ''Bf''AChE, ''Bungarus fasciatus'' AChE; HuAChE, human AChE; BoAChE, bovine AChE; MoAChE, mouse AChE; HdAChE, designed HuAChE, D4 variant<ref name="Goldenzweig">PMID:27425410</ref>; HuBChE, human BChE; ''Ag''AChE, ''Anopheles gambiae'' AChE; ''Dm''AChE, ''Drosophila melanogaster'' AChE.]] | ||
| - | Pocket in ''Bf''AChE that is homologous to the | + | Pocket in ''Bf''AChE that is homologous to the 4D pocket in ''Tc''AChE: |
*Crystal structure<ref name="Bourne">PMID:25411244</ref> (PDB code [[4qww]]), <scene name='87/876867/Cv/12'>showing three Asp residues, a Glu residue, and a water</scene>. | *Crystal structure<ref name="Bourne">PMID:25411244</ref> (PDB code [[4qww]]), <scene name='87/876867/Cv/12'>showing three Asp residues, a Glu residue, and a water</scene>. | ||
*Overlay of the ''Bf''AChE pocket (yellow sticks) on the ''Tc''AChE pocket (green sticks) with the distal oxygens displayed as red and green balls, respectively. | *Overlay of the ''Bf''AChE pocket (yellow sticks) on the ''Tc''AChE pocket (green sticks) with the distal oxygens displayed as red and green balls, respectively. | ||
Revision as of 15:23, 10 March 2021
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This page complements a publication in scientific journals and is one of the Proteopedia's Interactive 3D Complement pages. For aditional details please see I3DC.
