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1som - Proteopedia, life in 3D

1som

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TORPEDO CALIFORNICA ACETYLCHOLINESTERASE INHIBITED BY NERVE AGENT GD (SOMAN).

1som, resolution 2.20Å

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Structural highlights

1som is a 1 chain structure with sequence from Pacific electric ray. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands: , , Activity: Acetylcholinesterase, with EC number 3.1.1.7 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum

Function

[ACES_TORCA] Terminates signal transduction at the neuromuscular junction by rapid hydrolysis of the acetylcholine released into the synaptic cleft. May be involved in cell-cell interactions.

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

Organophosphorus acid anhydride (OP) nerve agents are potent inhibitors which rapidly phosphonylate acetylcholinesterase (AChE) and then may undergo an internal dealkylation reaction (called "aging") to produce an OP-enzyme conjugate that cannot be reactivated. To understand the basis for irreversible inhibition, we solved the structures of aged conjugates obtained by reaction of Torpedo californica AChE (TcAChE) with diisopropylphosphorofluoridate (DFP), O-isopropylmethylphosponofluoridate (sarin), or O-pinacolylmethylphosphonofluoridate (soman) by X-ray crystallography to 2.3, 2.6, or 2.2 A resolution, respectively. The highest positive difference density peak corresponded to the OP phosphorus and was located within covalent bonding distance of the active-site serine (S200) in each structure. The OP-oxygen atoms were within hydrogen-bonding distance of four potential donors from catalytic subsites of the enzyme, suggesting that electrostatic forces significantly stabilize the aged enzyme. The active sites of aged sarin- and soman-TcAChE were essentially identical and provided structural models for the negatively charged, tetrahedral intermediate that occurs during deacylation with the natural substrate, acetylcholine. Phosphorylation with DFP caused an unexpected movement in the main chain of a loop that includes residues F288 and F290 of the TcAChE acyl pocket. This is the first major conformational change reported in the active site of any AChE-ligand complex, and it offers a structural explanation for the substrate selectivity of AChE.

Crystal structures of aged phosphonylated acetylcholinesterase: nerve agent reaction products at the atomic level.,Millard CB, Kryger G, Ordentlich A, Greenblatt HM, Harel M, Raves ML, Segall Y, Barak D, Shafferman A, Silman I, Sussman JL Biochemistry. 1999 Jun 1;38(22):7032-9. PMID:10353814[1]

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

See Also

References

  1. Millard CB, Kryger G, Ordentlich A, Greenblatt HM, Harel M, Raves ML, Segall Y, Barak D, Shafferman A, Silman I, Sussman JL. Crystal structures of aged phosphonylated acetylcholinesterase: nerve agent reaction products at the atomic level. Biochemistry. 1999 Jun 1;38(22):7032-9. PMID:10353814 doi:[dx.doi.org]

Contents


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OCA

Retrieved from "[proteopedia.org]"

Categories: Acetylcholinesterase | Pacific electric ray | Greenblatt, H M | Millard, C B | Silman, I | Sussman, J L | Cholinesterase | Nerve agent | Organophosphorous acid anhydride | Serine hydrolase

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