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2wfz

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2wfz, resolution 1.95Å ()
Ligands: , , , , , ,
Activity: Acetylcholinesterase, with EC number 3.1.1.7
Related: 1zgb, 1amn, 1qti, 1e66, 2vq6, 2ack, 2j3d, 1qii, 2ckm, 1dx6, 1qij, 1qie, 1acl, 1w4l, 1odc, 2cmf, 1gqs, 2j3q, 1e3q, 2j4f, 2dfp, 1qik, 2c5f, 1ea5, 1eea, 1qif, 2vjc, 2vjb, 1qig, 1qid, 1zgc, 2vjd, 1jjb, 1ut6, 2vt6, 2w9i, 2vt7, 2cek, 1qim, 1gpk, 1jga, 3ace, 1oce, 1w6r, 1som, 1vxo, 2w6c, 2vja, 1cfj, 2v96, 1ax9, 1u65, 1w76, 1h22, 1eve, 2c4h, 2ace, 2va9, 1gqr, 1vxr, 4ace, 2c58, 1hbj, 1w75, 1vot, 2c5g, 2v98, 1jgb, 1gpn, 1qih, 1h23, 1acj, 1fss, 2v97, 2wg2, 2wg1, 2wg0
Resources: FirstGlance, OCA, RCSB, PDBsum
Coordinates: save as pdb, mmCIF, xml


Contents

NON-AGED CONJUGATE OF TORPEDO CALIFORNICA ACETYLCHOLINESTERASE WITH SOMAN

Publication Abstract from PubMed

Organophosphate compounds (OP) are potent inhibitors of acetylcholinesterases (AChEs) and can cause lethal poisoning in humans. Inhibition of AChEs by the OP soman involves phosphonylation of the catalytic serine, and subsequent dealkylation produces a form known as the "aged" enzyme. The nonaged form can be reactivated to a certain extent by nucleophiles, such as pralidoxime (2-PAM), whereas aged forms of OP-inhibited AChEs are totally resistant to reactivation. Here, we solved the X-ray crystal structures of AChE from Torpedo californica (TcAChE) conjugated with soman before and after aging. The absolute configuration of the soman stereoisomer adduct in the nonaged conjugate is P(S)C(R). A structural reorientation of the catalytic His440 side chain was observed during the aging process. Furthermore, the crystal structure of the ternary complex of the aged conjugate with 2-PAM revealed that the orientation of the oxime function does not permit nucleophilic attack on the phosphorus atom, thus providing a plausible explanation for its failure to reactivate the aged soman/AChE conjugate. Together, these three crystal structures provide an experimental basis for the design of new reactivators.

Crystallographic Snapshots of Nonaged and Aged Conjugates of Soman with Acetylcholinesterase, and of a Ternary Complex of the Aged Conjugate with Pralidoxime (dagger)., Sanson B, Nachon F, Colletier JP, Froment MT, Toker L, Greenblatt HM, Sussman JL, Ashani Y, Masson P, Silman I, Weik M, J Med Chem. 2009 Jul 30. PMID:19642642

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

About this Structure

2wfz is a 1 chain structure with sequence from Torpedo californica. Full crystallographic information is available from OCA.

See Also

Reference

  • Sanson B, Nachon F, Colletier JP, Froment MT, Toker L, Greenblatt HM, Sussman JL, Ashani Y, Masson P, Silman I, Weik M. Crystallographic Snapshots of Nonaged and Aged Conjugates of Soman with Acetylcholinesterase, and of a Ternary Complex of the Aged Conjugate with Pralidoxime (dagger). J Med Chem. 2009 Jul 30. PMID:19642642 doi:10.1021/jm900433t

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