Journal:Protein Science:4
From Proteopedia
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<big>Lushchekina, Weiner, Ashani, Emrizal, Firdaus-Raih, Silman & Sussman</big><ref>PMID: 39548604</ref> | <big>Lushchekina, Weiner, Ashani, Emrizal, Firdaus-Raih, Silman & Sussman</big><ref>PMID: 39548604</ref> | ||
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| - | [[Image:2024_Lushchekina_Prot_Sci_x.jpg| thumb |left|175px|Comparison of a divalent cation being <i>pulled</i> out of a 4A vs a 4A/3B motif [https://doi.org/10.1002/pro.5206 Go to paper]]] <b>Molecular Tour</b><br>''Torpedo californica'' acetylcholinesterase (''Tc''AChE) contains a unique 4D motif composed of four aspartate residues that can bind divalent metal cations (like Ca²⁺, Mg²⁺, Mn²⁺), significantly increasing the enzyme’s thermal stability. Despite the electrostatic repulsion expected between these ]aspartates, structural analysis shows that the enzyme's conformation remains stable <scene name='10/1063617/009_fig_metal_tcache_lab_png/2'>with</scene> or <scene name='10/1063617/009_fig_apo_tcache_lab_png/2'>without</scene> bound cations as seen in an <scene name='10/1063617/009_fig_metal_apo_tcache_lab/2'>overlay</scene> the two states and an <jmol> | + | [[Image:2024_Lushchekina_Prot_Sci_x.jpg| thumb |left|175px|Comparison of a divalent cation being <i>pulled</i> out of a 4A vs a 4A/3B motif [https://doi.org/10.1002/pro.5206 Go to paper]]] <b>Molecular Tour</b><br>''Torpedo californica'' acetylcholinesterase (''Tc''AChE) contains a unique 4D motif composed of four aspartate residues that can bind divalent metal cations (like Ca²⁺, Mg²⁺, Mn²⁺), significantly increasing the enzyme’s thermal stability. Despite the electrostatic repulsion expected between these ]aspartates, structural analysis shows that the enzyme's conformation remains stable <scene name='10/1063617/009_fig_metal_tcache_lab_png/2'>with</scene> or <scene name='10/1063617/009_fig_apo_tcache_lab_png/2'>without</scene> bound cations as seen in an <scene name='10/1063617/009_fig_metal_apo_tcache_lab/2'>overlay</scene> the two states and an |
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</jmol> between them. The stability of the 4D motif is attributed to adjacent positively charged residues (Lys325, Arg388, and Arg517), forming stabilizing salt bridges, leading to the newly named <scene name='10/1063617/009_fig_5b_new_450_450/1'>4A/3B motif</scene> (four acidic residues stabilized by three basic residues). | </jmol> between them. The stability of the 4D motif is attributed to adjacent positively charged residues (Lys325, Arg388, and Arg517), forming stabilizing salt bridges, leading to the newly named <scene name='10/1063617/009_fig_5b_new_450_450/1'>4A/3B motif</scene> (four acidic residues stabilized by three basic residues). | ||
| - | The study also identified additional metal-binding sites (His264 and His471 sites) in ''Tc''AChE through crystallographic analysis, but these appear to be weaker or crystallographic artifacts. Using metadynamics and molecular dynamics (MD) simulations with quantum potentials (QM/MM-MD), the binding strength of metal cations at the 4D site was compared to that of the 4D site in human fibrin-stabilizing factor (fXIIIa), which lacks stabilizing cationic residues. Results showed that while ''Tc''AChE’s 4A/3B motif maintains structural integrity upon metal binding/unbinding, the <scene name='10/1063617/009_fig_8a_new_jmol_def/1'>fXIIIa motif </scene> is stable in presence of a metal ion but <scene name='10/1063617/009_fig_8b_new_def_jmol/1'>explodes</scene> without a metal ions due to electrostatic repulsion. This is seen clearly in an | + | The study also identified additional metal-binding sites (His264 and His471 sites) in ''Tc''AChE through crystallographic analysis, but these appear to be weaker or crystallographic artifacts. Using metadynamics and molecular dynamics (MD) simulations with quantum potentials (QM/MM-MD), the binding strength of metal cations at the 4D site was compared to that of the 4D site in human fibrin-stabilizing factor (fXIIIa), which lacks stabilizing cationic residues. Results showed that while ''Tc''AChE’s 4A/3B motif maintains structural integrity upon metal binding/unbinding, the <scene name='10/1063617/009_fig_8a_new_jmol_def/1'>fXIIIa motif </scene> is stable in presence of a metal ion but <scene name='10/1063617/009_fig_8b_new_def_jmol/1'>explodes</scene> without a metal ions due to electrostatic repulsion. This is seen clearly in an <jmol> |
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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.
