1acj

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1acj, resolution 2.80Å ()
Ligands:
Activity: Acetylcholinesterase, with EC number 3.1.1.7
Resources: FirstGlance, OCA, RCSB, PDBsum
Coordinates: save as pdb, mmCIF, xml


Contents

QUATERNARY LIGAND BINDING TO AROMATIC RESIDUES IN THE ACTIVE-SITE GORGE OF ACETYLCHOLINESTERASE

Publication Abstract from PubMed

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.

Quaternary ligand binding to aromatic residues in the active-site gorge of acetylcholinesterase., Harel M, Schalk I, Ehret-Sabatier L, Bouet F, Goeldner M, Hirth C, Axelsen PH, Silman I, Sussman JL, Proc Natl Acad Sci U S A. 1993 Oct 1;90(19):9031-5. PMID:8415649

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

About this Structure

1acj is a 1 chain structure with sequence from Torpedo californica. The June 2004 RCSB PDB Molecule of the Month feature on Acetylcholinesterase by David S. Goodsell is 10.2210/rcsb_pdb/mom_2004_6. Full crystallographic information is available from OCA.

See Also

Reference

  • Harel M, Schalk I, Ehret-Sabatier L, Bouet F, Goeldner M, Hirth C, Axelsen PH, Silman I, Sussman JL. Quaternary ligand binding to aromatic residues in the active-site gorge of acetylcholinesterase. Proc Natl Acad Sci U S A. 1993 Oct 1;90(19):9031-5. PMID:8415649

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