PDBsum entry: 1fss

Complex (serine esterase/toxin)

PDB id: 1fss

Contents

Protein chains

532 a.a. *

61 a.a. *

Ligands

NAG

Metals

_ZN ×2

Waters ×36

* Residue conservation analysis

PDB id:

1fss

Name:

Complex (serine esterase/toxin)

Title:

Acetylcholinesterase (E.C. 3.1.1.7) complexed with fasciculi

Structure:

Acetylcholinesterase. Chain: a. Fasciculin ii. Chain: b

Source:

Torpedo californica. Pacific electric ray. Organism_taxid: 7787. Variant: g2 form. Organ: electric organ. Tissue: electroplaque. Dendroaspis angusticeps. Eastern green mamba. Organism_taxid: 8618.

Biol. unit:

Dimer (from PQS)

Resolution:

3.00Å R-factor: 0.230 R-free: 0.310

Authors:

M.Harel,G.J.Kleywegt,I.Silman,J.L.Sussman

Key ref:

M.Harel et al. (1995). Crystal structure of an acetylcholinesterase-fasciculin complex: interaction of a three-fingered toxin from snake venom with its target. Structure, 3, 1355-1366. PubMed id: 8747462 DOI: 10.1016/S0969-2126(01)00273-8

Date:

25-Oct-95 Release date: 08-Mar-96

Protein chain

P04058  (ACES_TORCA) -  Acetylcholinesterase

Seq: 586 a.a.

Struc: 532 a.a.

Protein chain

P0C1Z0  (TXFA2_DENAN) -  Fasciculin-2

Seq: 61 a.a.

Struc: 61 a.a.

Enzyme reactions

• Enzyme class: Chain A: E.C.3.1.1.7 - Acetylcholinesterase.
• Reaction: Acetylcholine + H₂O = choline + acetate

Acetylcholine (Bound ligand (Het Group name = NAG) matches with 41.18% similarity) + H(2)O = choline + acetate

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

 Gene Ontology (GO) functional annotation 

• Cellular component: synapse (7 terms)
• Biological process: modification of morphology or physiology of other organism (3 terms)
• Biochemical function: hydrolase activity (4 terms)

reference

DOI no: 10.1016/S0969-2126(01)00273-8

Structure 3:1355-1366 (1995)

PubMed id: 8747462

Crystal structure of an acetylcholinesterase-fasciculin complex: interaction of a three-fingered toxin from snake venom with its target.

M.Harel, G.J.Kleywegt, R.B.Ravelli, I.Silman, J.L.Sussman.

ABSTRACT

BACKGROUND: Fasciculin (FAS), a 61-residue polypeptide purified from mamba venom, is a three-fingered toxin which is a powerful reversible inhibitor of acetylcholinesterase (AChE). Solution of the three-dimensional structure of the AChE/FAS complex would provide the first structure of a three-fingered toxin complexed with its target. RESULTS: The structure of a complex between Torpedo californica AChE and fasciculin-II (FAS-II), from the venom of the green mamba (Dendroaspis angusticeps) was solved by molecular replacement techniques, and refined at 3.0 A resolution to an R-factor of 0.231. The structure reveals a stoichiometric complex with one FAS molecule bound to each AChE subunit. The AChE and FAS conformations in the complex are very similar to those in their isolated structures. FAS is bound at the 'peripheral' anionic site of AChE, sealing the narrow gorge leading to the active site, with the dipole moments of the two molecules roughly aligned. The high affinity of FAS for AChE is due to a remarkable surface complementarity, involving a large contact area (approximately 2000 A2) and many residues either unique to FAS or rare in other three-fingered toxins. The first loop, or finger, of FAS reaches down the outer surface of the thin aspect of the gorge. The second loop inserts into the gorge, with an unusual stacking interaction between Met33 in FAS and Trp279 in AChE. The third loop points away from the gorge, but the C-terminal residue makes contact with the enzyme. CONCLUSIONS: Two conserved aromatic residues in the AChE peripheral anionic site make important contacts with FAS. The absence of these residues from chicken and insect AChEs and from butyrylcholinesterase explains the very large reduction in the affinity of these enzymes for FAS. Several basic residues in FAS make important contacts with AChE. The complementarity between FAS and AChE is unusual, inasmuch as it involves a number of charged residues, but lacks any intermolecular salt linkages.

Selected figure(s)

Figure 3.
Figure 3. . Details of the AChE/FAS-II interface with interacting residues shown as ball-and-stick models. The letters ‘a’ or ‘f’ after the residue number refer to AChE and FAS-II, respectively. (a) Region A covering AChE residues 68–90, showing the large number of hydrophobic interactions. (b) Region B, covering AChE residues 271–289. Figure 3. . Details of the AChE/FAS-II interface with interacting residues shown as ball-and-stick models. The letters ‘a’ or ‘f’ after the residue number refer to AChE and FAS-II, respectively. (a) Region A covering AChE residues 68–90, showing the large number of hydrophobic interactions. (b) Region B, covering AChE residues 271–289.

Figure 8.
Figure 8. . Isopotential electrostatic surface looking straight into the active-site gorge of AChE, contoured at ±1 kT e^−1. Negative surface potential is shown in red and positive in blue. (a) AChE alone showing the deep gorge, with red surface over the gorge. (b) AChE/FAS-II complex showing FAS-II covering the gorge. Figure 8. . Isopotential electrostatic surface looking straight into the active-site gorge of AChE, contoured at ±1 kT e^−1. Negative surface potential is shown in red and positive in blue. (a) AChE alone showing the deep gorge, with red surface over the gorge. (b) AChE/FAS-II complex showing FAS-II covering the gorge.

The above figures are reprinted by permission from Cell Press: Structure (1995, 3, 1355-1366) copyright 1995.

Figures were selected by the author.