Journal:Protein Science:3
From Proteopedia
(Difference between revisions)

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The 4D motif is a novel motif, which has not been described before. The ASSAM server <ref>[http://27.126.156.175/assam ASSAM] Amino acid pattern Search for Substructures And Motifs</ref>, 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. | The 4D motif is a novel motif, which has not been described before. The ASSAM server <ref>[http://27.126.156.175/assam ASSAM] Amino acid pattern Search for Substructures And Motifs</ref>, 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: | + | '''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 4D 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 4D 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 4D pocket in ''Tc''AChE: | + | '''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>. | ||
*<scene name='87/876867/Cv/13'>Overlay of the BfAChE pocket (yellow sticks) on the TcAChE pocket (green sticks)</scene> with the distal oxygens displayed as red and green balls, respectively. | *<scene name='87/876867/Cv/13'>Overlay of the BfAChE pocket (yellow sticks) on the TcAChE pocket (green sticks)</scene> with the distal oxygens displayed as red and green balls, respectively. | ||
- | 4D motifs in four proteins retrieved from the ASSAM server: | + | '''4D motifs in four proteins retrieved from the ASSAM server:''' |
*<scene name='87/876867/Cv/20'>Bacillus subtilis phosphodiesterase PhoD, containing two Ca+2 ions</scene> (PDB code [[2yeq]])<ref name="Bacillus">PMID:25217636</ref>. | *<scene name='87/876867/Cv/20'>Bacillus subtilis phosphodiesterase PhoD, containing two Ca+2 ions</scene> (PDB code [[2yeq]])<ref name="Bacillus">PMID:25217636</ref>. | ||
*<scene name='87/876867/Cv/23'>Proton pyrophosphatase, containing three Mg+2 ions</scene> (PDB code [[4a01]])<ref name="pyrophosph">PMID:22456709</ref>. | *<scene name='87/876867/Cv/23'>Proton pyrophosphatase, containing three Mg+2 ions</scene> (PDB code [[4a01]])<ref name="pyrophosph">PMID:22456709</ref>. | ||
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<scene name='87/876867/Cv/29'>Overlays of the 4D motifs in TcAChE</scene>. All metal ions and waters are removed, and only the Asp residues are displayed in stick format. Apo ''Tc''AChE in green; Ca<sup>+2</sup>/''Tc''AChE in red; Mg<sup>+2</sup>/''Tc''AChE in blue; UO<sub>2</sub><sup>+2</sup>/''Tc''AChE in yellow. | <scene name='87/876867/Cv/29'>Overlays of the 4D motifs in TcAChE</scene>. All metal ions and waters are removed, and only the Asp residues are displayed in stick format. Apo ''Tc''AChE in green; Ca<sup>+2</sup>/''Tc''AChE in red; Mg<sup>+2</sup>/''Tc''AChE in blue; UO<sub>2</sub><sup>+2</sup>/''Tc''AChE in yellow. | ||
- | Overlays on Apo ''Tc''AChE of the 4D motifs of the four proteins retrieved from the ASSAM server: | + | '''Overlays on Apo ''Tc''AChE of the 4D motifs of the four proteins retrieved from the ASSAM server:''' |
*<scene name='87/876867/Cv1/18'>Bacillus subtilis phosphodiesterase PhoD</scene> (PDB code [[2yeq]]). | *<scene name='87/876867/Cv1/18'>Bacillus subtilis phosphodiesterase PhoD</scene> (PDB code [[2yeq]]). | ||
*<scene name='87/876867/Cv1/19'>Proton pyrophosphatase</scene> (PDB code [[4a01]]). | *<scene name='87/876867/Cv1/19'>Proton pyrophosphatase</scene> (PDB code [[4a01]]). |
Revision as of 11:21, 21 March 2021
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