Sandbox 250: Difference between revisions

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Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

Joel L. Sussman, Allison Granberry, Jaime Prilusky

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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 alpha carbon backbone in complex with acetylcholine is shown here in green.
+<scene name='Sandbox_250/Ache_ach/5'>AChE</scene>is an alpha/beta hydrolase fold with an amino acid sequence of 4-535. ACh consists of an acytoxy group, ethylene group and a quaternary ammonium ion.
 The <scene name='Sandbox_250/Ache_ach/4'> 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.
-The <scene name='Sandbox_250/Active_site_gorge_cpk/5'>Peripheral Anionic Site</scene> includes trp279, tyr70, and tyr121. The residues, highlighted in <scene name='Sandbox_250/Active_site_gorge_cpk/6'>yellow</scene>, sit at the entrance of the gorge and help attract the quaternary ammonium ion of Ach to AChE.
+The Peripheral Anionic Site(PAS) includes trp279, tyr70, and tyr121. Initially, the positively charged quaternary ammonium ion of ACh is attracted to and binds to the PAS of AChE, highlighted in yellow.
-The <scene name='Sandbox_250/Active_site_gorge_cpk/7'>Catalytic Anionic Site</scene> includes trp84 and phe330. These residues, higlighted in <scene name='Sandbox_250/Active_site_gorge_cpk/8'>red</scene>, hold ACh in the optimal position for hyrdrolysis.
+The Catalytic Anionic Site(CAS) includes trp84 and phe330. The CAS, highlighted in red, holds ACh in the optimal position for hydrolysis by interacting with the quaternary ammonium ion of ACh.
-The <scene name='Sandbox_250/Active_site_gorge_cpk/9'>Catalytic Triad</scene> or active site includes glu327, his440 and ser200. These residues, highlighted in <scene name='Sandbox_250/Active_site_gorge_cpk/10'>blue</scene>, are responsible for the hydrolysis of ACh into acetate and choline.
+The active site includes three residues: glu327, his440 and ser200. The Catalytic triad, highlithed in blue, is responsible for the hydrolysis of ACh into acetate and choline.
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 ===='''Features of the Inhibition Story'''====
-FAS-II <scene name='Sandbox/Ache_1fss/1'>amino acids 1-61</scene> were illustrated in an alpha carbon backbone. The alpha carbon backbone of FAS-II has 4 beta sheets forming three loops or fingers.
+FAS-II is a 61-residue polypeptide with 4 beta sheets forming three loops or fingers.
-The residues <scene name='Sandbox_250/Ache_fas2/3'>Thr8, Met33, Arg27 and Val34</scene> are present on two loops of the toxin FAS-II.
-When FAS-II <scene name='Sandbox_250/Ache_fas2/7'>binds</scene> to AChE, Arg27 and Met33 interact with trp279 of the Peripheral Anionic Site, while Val34 and Thr8 interact with tyr70 of the Peripheral Anionic Site. Once this interaction occurs, the entrance of the gorge is <scene name='Sandbox_250/Ache_fas2/8'>covered</scene> such that acetylcholine may not enter.
+FAS-II is attracted to AChE by a number of mechanisms:
+. Amino acid specificity: Thr8, Met33, Arg27 and Val34 are located on two of the three fingers of the FAS-II. When FAS-II binds to AChE, Arg27 and Met33 interact with Trp279 of the Peripheral Anionic Site, while Val34 and Thr8 interact with Tyr70 of the Peripheral Anionic Site.
+. Shape: Once bound to the PAS, two loops of FAS-II fit in to the active-site gorge like a hand fits into a glove. Once this interaction occurs, the entrance of the gorge is blocked such that acetylcholine may not enter.