2C5G

Torpedo californica acetylcholinesterase in complex with 20mM thiocholine

Summary for 2C5G

• Entry DOI: 10.2210/pdb2c5g/pdb
• Related: 1ACJ 1ACL 1AMN 1AX9 1CFJ 1DX6 1E3Q 1E66 1EA5 1EEA 1EVE 1FSS 1GPK 1GPN 1GQR 1GQS 1H22 1H23 1HBJ 1JGA 1JGB 1JJB 1OCE 1ODC 1QID 1QIE 1QIF 1QIG 1QIH 1QII 1QIJ 1QIK 1QIM 1QTI 1SOM 1U65 1UT6 1VOT 1VXO 1VXR 1W4L 1W6R 1W75 1W76 1ZGB 1ZGC 2ACE 2ACK 2C4H 2C58 2C5F 2CEK 2CKM 2CMF 2DFP 3ACE 4ACE
• Descriptor: ACETYLCHOLINESTERASE, 2-(TRIMETHYLAMMONIUM)ETHYL THIOL, CHLORIDE ION, ... (6 entities in total)
• Functional Keywords: hydrolase, serine esterase, synapse, membrane, neurotransmitter cleavage, alpha/beta hydrolase, substrate hydrolysis, michaelis-menten complex, substrate inhibition, alternative splicing, glycoprotein, anchor, lipoprotein
• Biological source: TORPEDO CALIFORNICA (PACIFIC ELECTRIC RAY)
• Total number of polymer chains: 1
• Total formula weight: 61967.92

Authors

Colletier, J.P.,Fournier, D.,Greenblatt, H.M.,Sussman, J.L.,Zaccai, G.,Silman, I.,Weik, M. (deposition date: 2005-10-27, release date: 2006-06-14, Last modification date: 2024-11-06)

Primary citation

Colletier, J.P.,Fournier, D.,Greenblatt, H.M.,Stojan, J.,Sussman, J.L.,Zaccai, G.,Silman, I.,Weik, M.
Structural Insights Into Substrate Traffic and Inhibition in Acetylcholinesterase.
Embo J., 25:2746-, 2006

PubMed Abstract: 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.

PubMed: 16763558
DOI: 10.1038/SJ.EMBOJ.7601175

Experimental method

X-RAY DIFFRACTION (1.95 Å)