Sandbox 250
From Proteopedia
(New page: <table style="background-color:#ffffc0" cellpadding="8" width="95%" border="0"><tr><td>Please do NOT make changes to this Sandbox until after September 15, 2010. Sandboxes 250-265 are rese...) |
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| - | + | ==='''Designing a Physical Model to Tell the Story of Acetylcholinesterase'''=== | |
| + | Reflected in our design are two key concepts of AChE: the biochemistry of how the ACh overcomes the depth of the active site gorge before hydrolysis can occur, and how a toxin inhibits the substrate from finding the active site.Two physical models were designed and made by 3-dimensional printing technology: ''Torpedo californica (Tc)'' AChE in complex with a modeled ACh ligand, and ''Tc'' AChE in complex with FAS-II. Both models were based on protein data bank (PDB) files, and Rasmol computer modeling program. PDB files included PDB entry code 2ace for the ''Tc''AChE/ACh complex, and PDB entry code 1fss for the ''Tc'' AChE/FAS-II complex. | ||
| - | + | <applet load='2ace' size='300' frame='true' align='left' caption='AChE/ACh' /> | |
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| - | <scene name='Sandbox_90/Leut_with_labelled_residues/2'>LeuT labelled residues</scene><br> | ||
| + | ===='''Features of the Substrate Traffic Story: AChE/ACh'''==== | ||
| - | <scene name=' | + | AChE is an alpha/beta hydrolase fold with an amino acid sequence of 4-535. The <scene name='Sandbox/2ace/3'>alpha carbon backbone</scene> of AChE has ? alpha helices and ? beta sheets. |
| - | <scene name=' | + | The <scene name='Sandbox/Ache_ach/15'>14 aromatic residues</scene> that line the active site gorge are tyr70, trp84, trp120, tyr121, tyr130, trp233, trp279, phe288, phe290, phe330, phe331, tyr334, trp432 and tyr442. |
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| + | The <scene name='Sandbox/Ache_ach/14'>Catalytic Triad</scene> or active site includes glu327, his440 and ser200. Here is where Acetylcholine is hydrolyzed. | ||
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| + | Three of the aromatic residues that line the gorge attract the quaternary ammonium ion of ACh. These 3 aromatic residues, trp279, tyr70, and tyr121, sit at the entrance of the gorge and make up the <scene name='Sandbox/Ache_ach/13'>Peripheral Anionic Site</scene>. | ||
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| + | Two of the 14 aromatic residues lining the active site gorge that are considered significant for holding ACh in an optimal position for hydrolysis are trp84 and phe330. These residues form the <scene name='Sandbox/Ache_ach/16'>Catalytic Anionic Site</scene>. | ||
Revision as of 17:45, 3 August 2010
Designing a Physical Model to Tell the Story of Acetylcholinesterase
Reflected in our design are two key concepts of AChE: the biochemistry of how the ACh overcomes the depth of the active site gorge before hydrolysis can occur, and how a toxin inhibits the substrate from finding the active site.Two physical models were designed and made by 3-dimensional printing technology: Torpedo californica (Tc) AChE in complex with a modeled ACh ligand, and Tc AChE in complex with FAS-II. Both models were based on protein data bank (PDB) files, and Rasmol computer modeling program. PDB files included PDB entry code 2ace for the TcAChE/ACh complex, and PDB entry code 1fss for the Tc AChE/FAS-II complex.
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Features of the Substrate Traffic Story: AChE/ACh
AChE is an alpha/beta hydrolase fold with an amino acid sequence of 4-535. The of AChE has ? alpha helices and ? beta sheets.
The that line the active site gorge are tyr70, trp84, trp120, tyr121, tyr130, trp233, trp279, phe288, phe290, phe330, phe331, tyr334, trp432 and tyr442.
The or active site includes glu327, his440 and ser200. Here is where Acetylcholine is hydrolyzed.
Three of the aromatic residues that line the gorge attract the quaternary ammonium ion of ACh. These 3 aromatic residues, trp279, tyr70, and tyr121, sit at the entrance of the gorge and make up the .
Two of the 14 aromatic residues lining the active site gorge that are considered significant for holding ACh in an optimal position for hydrolysis are trp84 and phe330. These residues form the .
