2c5g: Difference between revisions
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==Overview== | ==Overview== | ||
Acetylcholinesterase (AChE) terminates nerve-impulse transmission at, cholinergic synapses by rapid hydrolysis of the neurotransmitter, acetylcholine. Substrate traffic in AChE involves at least two binding, sites, the catalytic and peripheral anionic sites, which have been, suggested to be allosterically related and involved in substrate, inhibition. Here, we present the crystal structures of Torpedo californica, AChE complexed with the substrate acetylthiocholine, the product, thiocholine and a nonhydrolysable substrate analogue. These structures, provide a series of static snapshots of the substrate en route to the, active site and identify, for the first time, binding of substrate and, product at both the peripheral and active sites. Furthermore, they provide, structural insight into ... | Acetylcholinesterase (AChE) terminates nerve-impulse transmission at, cholinergic synapses by rapid hydrolysis of the neurotransmitter, acetylcholine. Substrate traffic in AChE involves at least two binding, sites, the catalytic and peripheral anionic sites, which have been, suggested to be allosterically related and involved in substrate, inhibition. Here, we present the crystal structures of Torpedo californica, AChE complexed with the substrate acetylthiocholine, the product, thiocholine and a nonhydrolysable substrate analogue. These structures, provide a series of static snapshots of the substrate en route to the, active site and identify, for the first time, binding of substrate and, product at both the peripheral and active sites. Furthermore, they provide, structural insight into substrate inhibition in AChE at two different, substrate concentrations. Our structural data indicate that substrate, inhibition at moderate substrate concentration is due to choline exit, being hindered by a substrate molecule bound at the peripheral site. At, the higher concentration, substrate inhibition arises from prevention of, exit of acetate due to binding of two substrate molecules within the, active-site gorge. | ||
==About this Structure== | ==About this Structure== | ||
2C5G is a | 2C5G is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Torpedo_californica Torpedo californica] with NAG, CL, ETM and PGE as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Acetylcholinesterase Acetylcholinesterase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.1.7 3.1.1.7] Structure known Active Site: AC1. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=2C5G OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: synapse]] | [[Category: synapse]] | ||
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Revision as of 15:45, 5 November 2007
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TORPEDO CALIFORNICA ACETYLCHOLINESTERASE IN COMPLEX WITH 20MM THIOCHOLINE
OverviewOverview
Acetylcholinesterase (AChE) terminates nerve-impulse transmission at, cholinergic synapses by rapid hydrolysis of the neurotransmitter, acetylcholine. Substrate traffic in AChE involves at least two binding, sites, the catalytic and peripheral anionic sites, which have been, suggested to be allosterically related and involved in substrate, inhibition. Here, we present the crystal structures of Torpedo californica, AChE complexed with the substrate acetylthiocholine, the product, thiocholine and a nonhydrolysable substrate analogue. These structures, provide a series of static snapshots of the substrate en route to the, active site and identify, for the first time, binding of substrate and, product at both the peripheral and active sites. Furthermore, they provide, structural insight into substrate inhibition in AChE at two different, substrate concentrations. Our structural data indicate that substrate, inhibition at moderate substrate concentration is due to choline exit, being hindered by a substrate molecule bound at the peripheral site. At, the higher concentration, substrate inhibition arises from prevention of, exit of acetate due to binding of two substrate molecules within the, active-site gorge.
About this StructureAbout this Structure
2C5G is a Single protein structure of sequence from Torpedo californica with NAG, CL, ETM and PGE as ligands. Active as Acetylcholinesterase, with EC number 3.1.1.7 Structure known Active Site: AC1. Full crystallographic information is available from OCA.
ReferenceReference
Structural insights into substrate traffic and inhibition in acetylcholinesterase., Colletier JP, Fournier D, Greenblatt HM, Stojan J, Sussman JL, Zaccai G, Silman I, Weik M, EMBO J. 2006 Jun 21;25(12):2746-56. Epub 2006 Jun 8. PMID:16763558
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OCA- Pages with broken file links
- Acetylcholinesterase
- Single protein
- Torpedo californica
- Colletier, J.P.
- Fournier, D.
- Greenblatt, H.M.
- Silman, I.
- Sussman, J.L.
- Weik, M.
- Zaccai, G.
- CL
- ETM
- NAG
- PGE
- Alpha/beta hydrolase
- Alternative splicing
- Anchor
- Glycoprotein
- Hydrolase
- Lipoprotein
- Membrane
- Michaelis-menten complex
- Neurotransmitter cleavage
- Serine esterase
- Substrate hydrolysis
- Substrate inhibition
- Synapse