2WG2
NON-AGED CONJUGATE OF TORPEDO CALIFORNICA ACETYLCHOLINESTERASE WITH SOMAN (ALTERNATIVE REFINEMENT)
Summary for 2WG2
| Entry DOI | 10.2210/pdb2wg2/pdb |
| 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 2J3Q 2J4F 2V96 2V97 2V98 2VA9 2VJA 2VJB 2VJC 2VJD 2VQ6 2VT6 2VT7 2W6C 2W9I 2WFZ 2WG0 2WG1 3ACE 4ACE |
| Descriptor | ACETYLCHOLINESTERASE, alpha-L-fucopyranose-(1-6)-2-acetamido-2-deoxy-beta-D-glucopyranose, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (9 entities in total) |
| Functional Keywords | aging, hydrolase, cell membrane, neurotransmitter degradation, synapse membrane, alzheimer disease, gpi-anchor, glycoprotein, cell junction |
| Biological source | TORPEDO CALIFORNICA (PACIFIC ELECTRIC RAY) |
| Total number of polymer chains | 1 |
| Total formula weight | 63049.44 |
| Authors | Sanson, B.,Nachon, F.,Colletier, J.P.,Froment, M.T.,Toker, L.,Greenblatt, H.M.,Sussman, J.L.,Ashani, Y.,Masson, P.,Silman, I.,Weik, M. (deposition date: 2009-04-15, release date: 2010-04-21, Last modification date: 2023-12-13) |
| Primary citation | Sanson, B.,Nachon, F.,Colletier, J.P.,Froment, M.T.,Toker, L.,Greenblatt, H.M.,Sussman, J.L.,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. J.Med.Chem., 52:7593-, 2009 Cited by PubMed Abstract: 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. PubMed: 19642642DOI: 10.1021/JM900433T PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.95 Å) |
Structure validation
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