| Structural highlights
2w6c 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: | 1zgb, 1amn, 1qti, 1e66, 2vq6, 2ack, 2j3d, 1qii, 2ckm, 1dx6, 1qij, 1qie, 1acl, 1w4l, 1odc, 2cmf, 2j3q, 1gqs, 1e3q, 2j4f, 2dfp, 1qik, 2c5f, 1ea5, 2vjc, 1qif, 1eea, 2vjb, 1qig, 1qid, 1zgc, 1jjb, 2vjd, 1ut6, 2vt6, 2vt7, 2cek, 1qim, 1gpk, 1jga, 3ace, 1w6r, 1oce, 1som, 1vxo, 2vja, 1cfj, 2v96, 1u65, 1w76, 1ax9, 1h22, 1eve, 2c4h, 2ace, 2va9, 1gqr, 1vxr, 4ace, 2c58, 1hbj, 1w75, 1vot, 2c5g, 1jgb, 2v98, 1gpn, 1qih, 1h23, 1acj, 1fss, 2v97 |
| Activity: | Acetylcholinesterase, with EC number 3.1.1.7 |
| Resources: | FirstGlance, OCA, RCSB, PDBsum |
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
A bis-(-)-nor-meptazinol derivative in which the two meptazinol rings are linked by a nonamethylene spacer is a novel acetylcholinesterase inhibitor that inhibits both catalytic activity and Abeta peptide aggregation. The crystal structure of its complex with Torpedo californica acetylcholinesterase was determined to 2.7 A resolution. The ligand spans the active-site gorge, with one nor-meptazinol moiety bound at the "anionic" subsite of the active site, disrupting the catalytic triad by forming a hydrogen bond with His440N(epsilon2), which is hydrogen-bonded to Ser200O(gamma) in the native enzyme. The second nor-meptazinol binds at the peripheral "anionic" site at the gorge entrance. A number of GOLD models of the complex, using both native TcAChE and the protein template from the crystal structure of the bis-(-)-nor-meptazinol/TcAChE complex, bear higher similarity to the X-ray structure than a previous model obtained using the mouse enzyme structure. These findings may facilitate rational design of new meptazinol-based acetylcholinesterase inhibitors.
The Crystal Structure of a Complex of Acetylcholinesterase with a Bis-(-)-nor-meptazinol Derivative Reveals Disruption of the Catalytic Triad.,Paz A, Xie Q, Greenblatt HM, Fu W, Tang Y, Silman I, Qiu Z, Sussman JL J Med Chem. 2009 Mar 27. PMID:19326912[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Paz A, Xie Q, Greenblatt HM, Fu W, Tang Y, Silman I, Qiu Z, Sussman JL. The Crystal Structure of a Complex of Acetylcholinesterase with a Bis-(-)-nor-meptazinol Derivative Reveals Disruption of the Catalytic Triad. J Med Chem. 2009 Mar 27. PMID:19326912 doi:10.1021/jm801657v
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