{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T10:22:35Z","timestamp":1792491755334,"version":"4.5.0"},"reference-count":0,"publisher":"National Academy of Sciences","issue":"19","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[1993,10]]},"abstract":"<jats:p>Binding sites of Torpedo acetylcholinesterase (EC 3.1.1.7) for quaternary ligands were investigated by x-ray crystallography and photoaffinity labeling. Crystal structures of complexes with ligands were determined at 2.8-A resolution. In a complex with edrophonium, and quaternary nitrogen of the ligand interacts with the indole of Trp-84, and its m-hydroxyl displays bifurcated hydrogen bonding to two members of the catalytic triad, Ser-200 and His-440. In a complex with tacrine, the acridine is stacked against the indole of Trp-84. The bisquaternary ligand decamethonium is oriented along the narrow gorge leading to the active site; one quaternary group is apposed to the indole of Trp-84 and the other to that of Trp-279, near the top of the gorge. The only major conformational difference between the three complexes is in the orientation of the phenyl ring of Phe-330. In the decamethonium complex it lies parallel to the surface of the gorge; in the other two complexes it is positioned to make contact with the bound ligand. This close interaction was confirmed by photoaffinity labelling by the photosensitive probe 3H-labeled p-(N,N-dimethylamino)benzenediazonium fluoroborate, which labeled, predominantly, Phe-330 within the active site. Labeling of Trp-279 was also observed. One mole of label is incorporated per mole of AcChoEase inactivated, indicating that labeling of Trp-279 and that of Phe-330 are mutually exclusive. The structural and chemical data, together, show the important role of aromatic groups as binding sites for quaternary ligands, and they provide complementary evidence assigning Trp-84 and Phe-330 to the \"anionic\" subsite of the active site and Trp-279 to the \"peripheral\" anionic site.<\/jats:p>","DOI":"10.1073\/pnas.90.19.9031","type":"journal-article","created":{"date-parts":[[2006,5,31]],"date-time":"2006-05-31T08:32:31Z","timestamp":1149064351000},"page":"9031-9035","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":816,"title":["Quaternary ligand binding to aromatic residues in the active-site gorge of acetylcholinesterase."],"prefix":"10.1073","volume":"90","author":[{"given":"M","family":"Harel","sequence":"first","affiliation":[{"name":"Department of Structural Biology, Weizmann Institute of Science, Rehovot, Israel."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"I","family":"Schalk","sequence":"additional","affiliation":[{"name":"Department of Structural Biology, Weizmann Institute of Science, Rehovot, Israel."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L","family":"Ehret-Sabatier","sequence":"additional","affiliation":[{"name":"Department of Structural Biology, Weizmann Institute of Science, Rehovot, Israel."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F","family":"Bouet","sequence":"additional","affiliation":[{"name":"Department of Structural Biology, Weizmann Institute of Science, Rehovot, Israel."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M","family":"Goeldner","sequence":"additional","affiliation":[{"name":"Department of Structural Biology, Weizmann Institute of Science, Rehovot, Israel."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C","family":"Hirth","sequence":"additional","affiliation":[{"name":"Department of Structural Biology, Weizmann Institute of Science, Rehovot, Israel."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P H","family":"Axelsen","sequence":"additional","affiliation":[{"name":"Department of Structural Biology, Weizmann Institute of Science, Rehovot, Israel."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"I","family":"Silman","sequence":"additional","affiliation":[{"name":"Department of Structural Biology, Weizmann Institute of Science, Rehovot, Israel."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J L","family":"Sussman","sequence":"additional","affiliation":[{"name":"Department of Structural Biology, Weizmann Institute of Science, Rehovot, Israel."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[1993,10]]},"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.90.19.9031","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,13]],"date-time":"2022-04-13T13:47:31Z","timestamp":1649857651000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.90.19.9031"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1993,10]]},"references-count":0,"journal-issue":{"issue":"19","published-print":{"date-parts":[[1993,10]]}},"alternative-id":["10.1073\/pnas.90.19.9031"],"URL":"https:\/\/doi.org\/10.1073\/pnas.90.19.9031","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[1993,10]]},"assertion":[{"value":"1993-10-01","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}