2j3q

TORPEDO ACETYLCHOLINESTERASE COMPLEXED WITH FLUOROPHORE THIOFLAVIN TTORPEDO ACETYLCHOLINESTERASE COMPLEXED WITH FLUOROPHORE THIOFLAVIN T

Structural highlights 2j3q is a 1 chain structure with sequence from Torpedo californica. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: , , , 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, 2c5g, 2cek, 2ckm, 2cmf, 2dfp, 2j3d, 3ace, 4ace Activity: Acetylcholinesterase, with EC number 3.1.1.7 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum Function [ACES_TORCA] Terminates signal transduction at the neuromuscular junction by rapid hydrolysis of the acetylcholine released into the synaptic cleft. May be involved in cell-cell interactions. Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMed Acetylcholinesterase plays a key role in cholinergic synaptic transmission by hydrolyzing the neurotransmitter acetylcholine with one of the highest known catalytic rate constants. Hydrolysis occurs in a narrow and deep gorge that contains two sites of ligand binding: A peripheral site, or P-site, near the gorge entrance that contributes to catalytic efficiency both by transiently trapping substrate molecules as they enter the gorge and by allosterically accelerating the transfer of the substrate acyl group to a serine hydroxyl in an acylation site or A-site at the base of the gorge. Thioflavin T is a useful reporter of ligand interactions with the A-site. It binds specifically to the P-site with fluorescence that is enhanced approximately 1000-fold over that of unbound thioflavin T, and the enhanced fluorescence is quenched 1.5- to 4-fold when another ligand binds to the A-site in a ternary complex. To clarify the structural basis of this advantageous signal change, we here report the X-ray structure of the complex of thioflavin T with Torpedo californica acetylcholinesterase. The two aromatic rings in thioflavin T are coplanar and are packed snugly parallel to the aromatic side chains of Trp279, Tyr334, and Phe330. Overlays of this structure with the crystal structures of Torpedo californica acetylcholinesterase complexes with either edrophonium or m-( N, N, N-trimethylammonio)-2,2,2-trifluoroacetophenone, two small aromatic ligands that bind specifically to the A-site, indicate that the phenyl side chain of Phe330 must rotate to sterically accommodate both thioflavin T and the A-site ligand in the ternary complex. This rotation may allow some relaxation of the strict coplanarity of the aromatic rings in the bound thioflavin T and result in partial quenching of its fluorescence. Crystal structure of thioflavin T bound to the peripheral site of Torpedo californica acetylcholinesterase reveals how thioflavin T acts as a sensitive fluorescent reporter of ligand binding to the acylation site.,Harel M, Sonoda LK, Silman I, Sussman JL, Rosenberry TL J Am Chem Soc. 2008 Jun 25;130(25):7856-61. Epub 2008 May 31. PMID:18512913 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also AChE inhibitors and substrates Acetylcholinesterase Journal:Protein Science:1

spinqualitylabelsall models 2j3q, resolution 2.80Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image