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PDBsum entry 1qon

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Hydrolase PDB id
1qon
Jmol
Contents
Protein chain
540 a.a. *
Ligands
SO4
NAG-NAG-BMA-BMA-
BMA
I40
Waters ×139
* Residue conservation analysis
PDB id:
1qon
Name: Hydrolase
Title: Ache from drosophila melanogaster complex with tacrine derivative 9-(3-iodobenzylamino)-1,2,3,4-tetrahydroacridine
Structure: Acetylcholinesterase. Chain: a. Engineered: yes
Source: Drosophila melanogaster. Fruit fly. Organism_taxid: 7227. Expressed in: drosophila melanogaster. Expression_system_taxid: 7227. (Extracellular).
Resolution:
2.72Å     R-factor:   0.220     R-free:   0.265
Authors: M.Harel,I.Silman,J.L.Sussman
Key ref: M.Harel et al. (2000). Three-dimensional structures of Drosophila melanogaster acetylcholinesterase and of its complexes with two potent inhibitors. Protein Sci, 9, 1063-1072. PubMed id: 10892800 DOI: 10.1110/ps.9.6.1063
Date:
15-Nov-99     Release date:   20-Jul-00    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P07140  (ACES_DROME) -  Acetylcholinesterase
Seq:
Struc:
 
Seq:
Struc:
649 a.a.
540 a.a.
Key:    PfamA domain  PfamB domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.3.1.1.7  - Acetylcholinesterase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: Acetylcholine + H2O = choline + acetate
Acetylcholine
Bound ligand (Het Group name = NAG)
matches with 41.00% similarity
+ H(2)O
= choline
+ acetate
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     synapse   6 terms 
  Biological process     synaptic transmission   7 terms 
  Biochemical function     hydrolase activity     4 terms  

 

 
    reference    
 
 
DOI no: 10.1110/ps.9.6.1063 Protein Sci 9:1063-1072 (2000)
PubMed id: 10892800  
 
 
Three-dimensional structures of Drosophila melanogaster acetylcholinesterase and of its complexes with two potent inhibitors.
M.Harel, G.Kryger, T.L.Rosenberry, W.D.Mallender, T.Lewis, R.J.Fletcher, J.M.Guss, I.Silman, J.L.Sussman.
 
  ABSTRACT  
 
We have crystallized Drosophila melanogaster acetylcholinesterase and solved the structure of the native enzyme and of its complexes with two potent reversible inhibitors, 1,2,3,4-tetrahydro-N-(phenylmethyl)-9-acridinamine and 1,2,3,4-tetrahydro-N-(3-iodophenyl-methyl)-9-acridinamine--all three at 2.7 A resolution. The refined structure of D. melanogaster acetylcholinesterase is similar to that of vertebrate acetylcholinesterases, for example, human, mouse, and fish, in its overall fold, charge distribution, and deep active-site gorge, but some of the surface loops deviate by up to 8 A from their position in the vertebrate structures, and the C-terminal helix is shifted substantially. The active-site gorge of the insect enzyme is significantly narrower than that of Torpedo californica AChE, and its trajectory is shifted several angstroms. The volume of the lower part of the gorge of the insect enzyme is approximately 50% of that of the vertebrate enzyme. Upon binding of either of the two inhibitors, nine aromatic side chains within the active-site gorge change their conformation so as to interact with the inhibitors. Some differences in activity and specificity between the insect and vertebrate enzymes can be explained by comparison of their three-dimensional structures.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
21305389 W.Kim, D.Lee, J.Choi, A.Kim, S.Han, K.Park, J.Choi, J.Kim, Y.Choi, S.H.Lee, and Y.H.Koh (2011).
Pharmacogenetic Regulation of Acetylcholinesterase Activity in Drosophila Reveals the Regulatory Mechanisms of AChE Inhibitors in Synaptic Plasticity.
  Neurochem Res, 36, 879-893.  
20146377 P.Zhao, K.Y.Zhu, and H.Jiang (2010).
Heterologous expression, purification, and biochemical characterization of a greenbug (Schizaphis graminum) acetylcholinesterase encoded by a paralogous gene (ace-1).
  J Biochem Mol Toxicol, 24, 51-59.  
19301127 A.A.Bernardo, and H.E.Bicudo (2009).
Variability of esterase patterns in adult flies of the saltans species group of Drosophila (subgenus Sophophora).
  Genetica, 137, 111-124.  
18986991 A.J.Powell, J.Tomberg, A.M.Deacon, R.A.Nicholas, and C.Davies (2009).
Crystal Structures of Penicillin-binding Protein 2 from Penicillin-susceptible and -resistant Strains of Neisseria gonorrhoeae Reveal an Unexpectedly Subtle Mechanism for Antibiotic Resistance.
  J Biol Chem, 284, 1202-1212.
PDB codes: 3equ 3eqv
19263097 F.Fan, Z.You, Z.Li, J.Cheng, Y.Tang, and Z.Tang (2009).
A butterfly effect: highly insecticidal resistance caused by only a conservative residue mutated of drosophila melanogaster acetylcholinesterase.
  J Mol Model, 15, 1229-1236.  
19016914 F.Nardi, B.Barazzuoli, S.Ciolfi, A.Carapelli, R.Dallai, and F.Frati (2009).
Acetylcholinesterase genes in the basal Hexapod Orchesella villosa.
  Insect Mol Biol, 18, 45-54.  
19607916 H.Jiang, S.Liu, P.Zhao, and C.Pope (2009).
Recombinant expression and biochemical characterization of the catalytic domain of acetylcholinesterase-1 from the African malaria mosquito, Anopheles gambiae.
  Insect Biochem Mol Biol, 39, 646-653.  
19335834 R.A.Carvalho, T.T.Torres, M.G.Paniago, and A.M.Azeredo-Espin (2009).
Molecular characterization of esterase E3 gene associated with organophosphorus insecticide resistance in the New World screwworm fly, Cochliomyia hominivorax.
  Med Vet Entomol, 23, 86-91.  
19656357 V.Corbel, M.Stankiewicz, C.Pennetier, D.Fournier, J.Stojan, E.Girard, M.Dimitrov, J.Molgó, J.M.Hougard, and B.Lapied (2009).
Evidence for inhibition of cholinesterases in insect and mammalian nervous systems by the insect repellent deet.
  BMC Biol, 7, 47.  
17921202 A.A.Gorfe, C.E.Chang, I.Ivanov, and J.A.McCammon (2008).
Dynamics of the acetylcholinesterase tetramer.
  Biophys J, 94, 1144-1154.  
18384763 M.Rowland, I.Tsigelny, M.Wolfe, and L.Pezzementi (2008).
Inactivation of an invertebrate acetylcholinesterase by sulfhydryl reagents: a reconsideration of the implications for insecticide design.
  Chem Biol Interact, 175, 73-75.  
18974885 S.Biswas, R.J.Russell, C.J.Jackson, M.Vidovic, O.Ganeshina, J.G.Oakeshott, and C.Claudianos (2008).
Bridging the synaptic gap: neuroligins and neurexin I in Apis mellifera.
  PLoS ONE, 3, e3542.  
18359854 Y.Xu, J.P.Colletier, H.Jiang, I.Silman, J.L.Sussman, and M.Weik (2008).
Induced-fit or preexisting equilibrium dynamics? Lessons from protein crystallography and MD simulations on acetylcholinesterase and implications for structure-based drug design.
  Protein Sci, 17, 601-605.  
18502801 Y.Xu, J.P.Colletier, M.Weik, H.Jiang, J.Moult, I.Silman, and J.L.Sussman (2008).
Flexibility of aromatic residues in the active-site gorge of acetylcholinesterase: X-ray versus molecular dynamics.
  Biophys J, 95, 2500-2511.  
17681228 A.L.Devonshire, R.Heidari, H.Z.Huang, B.D.Hammock, R.J.Russell, and J.G.Oakeshott (2007).
Hydrolysis of individual isomers of fluorogenic pyrethroid analogs by mutant carboxylesterases from Lucilia cuprina.
  Insect Biochem Mol Biol, 37, 891-902.  
17175445 H.Alout, A.Berthomieu, A.Hadjivassilis, and M.Weill (2007).
A new amino-acid substitution in acetylcholinesterase 1 confers insecticide resistance to Culex pipiens mosquitoes from Cyprus.
  Insect Biochem Mol Biol, 37, 41-47.  
17546082 M.H.Chen, Z.J.Han, X.F.Qiao, and M.J.Qu (2007).
Mutations in acetylcholinesterase genes of Rhopalosiphum padi resistant to organophosphate and carbamate insecticides.
  Genome, 50, 172-179.  
16636921 A.P.Nascimento, and H.E.Bicudo (2006).
Further study on the esterase patterns of sibling species in the Drosophila saltans subgroup (saltans group): intraspecific and interspecific variations in the development.
  Genetica, 126, 265-276.  
17069637 C.Claudianos, H.Ranson, R.M.Johnson, S.Biswas, M.A.Schuler, M.R.Berenbaum, R.Feyereisen, and J.G.Oakeshott (2006).
A deficit of detoxification enzymes: pesticide sensitivity and environmental response in the honeybee.
  Insect Mol Biol, 15, 615-636.  
16651186 J.C.Hsu, D.S.Haymer, W.J.Wu, and H.T.Feng (2006).
Mutations in the acetylcholinesterase gene of Bactrocera dorsalis associated with resistance to organophosphorus insecticides.
  Insect Biochem Mol Biol, 36, 396-402.  
16763558 J.P.Colletier, D.Fournier, H.M.Greenblatt, J.Stojan, J.L.Sussman, G.Zaccai, I.Silman, and M.Weik (2006).
Structural insights into substrate traffic and inhibition in acetylcholinesterase.
  EMBO J, 25, 2746-2756.
PDB codes: 2c4h 2c58 2c5f 2c5g
16586114 L.Pezzementi, M.Rowland, M.Wolfe, and I.Tsigelny (2006).
Inactivation of an invertebrate acetylcholinesterase by sulfhydryl reagents: the roles of two cysteines in the catalytic gorge of the enzyme.
  Invert Neurosci, 6, 47-55.  
16686937 O.R.Siadat, A.Lougarre, L.Lamouroux, C.Ladurantie, and D.Fournier (2006).
The effect of engineered disulfide bonds on the stability of Drosophila melanogaster acetylcholinesterase.
  BMC Biochem, 7, 12.  
16572227 P.J.Houghton, Y.Ren, and M.J.Howes (2006).
Acetylcholinesterase inhibitors from plants and fungi.
  Nat Prod Rep, 23, 181-199.  
16302258 S.Richter, J.Nieveler, H.Schulze, T.T.Bachmann, and R.D.Schmid (2006).
High yield production of a mutant Nippostrongylus brasiliensis acetylcholinesterase in Pichia pastoris and its purification.
  Biotechnol Bioeng, 93, 1017-1022.  
  16569291 M.E.Selkirk, O.Lazari, and J.B.Matthews (2005).
Functional genomics of nematode acetylcholinesterases.
  Parasitology, 131, S3-18.  
15251041 C.Strub, C.Alies, A.Lougarre, C.Ladurantie, J.Czaplicki, and D.Fournier (2004).
Mutation of exposed hydrophobic amino acids to arginine to increase protein stability.
  BMC Biochem, 5, 9.  
15378568 H.Reuveny, and E.Cohen (2004).
Evaluation of mechanisms of azinphos-methyl resistance in the codling moth Cydia pomonella (L.).
  Arch Insect Biochem Physiol, 57, 92.  
15030487 J.Stojan, L.Brochier, C.Alies, J.P.Colletier, and D.Fournier (2004).
Inhibition of Drosophila melanogaster acetylcholinesterase by high concentrations of substrate.
  Eur J Biochem, 271, 1364-1371.  
  15185924 K.B.Temeyer, R.B.Davey, and A.C.Chen (2004).
Identification of a third Boophilus microplus (Acari: Ixodidae) cDNA presumptively encoding an acetylcholinesterase.
  J Med Entomol, 41, 259-268.  
15018650 M.A.Shi, A.Lougarre, C.Alies, I.Frémaux, Z.H.Tang, J.Stojan, and D.Fournier (2004).
Acetylcholinesterase alterations reveal the fitness cost of mutations conferring insecticide resistance.
  BMC Evol Biol, 4, 5.  
15018651 P.Menozzi, M.A.Shi, A.Lougarre, Z.H.Tang, and D.Fournier (2004).
Mutations of acetylcholinesterase which confer insecticide resistance in Drosophila melanogaster populations.
  BMC Evol Biol, 4, 4.  
15373811 S.Toda, S.Komazaki, T.Tomita, and Y.Kono (2004).
Two amino acid substitutions in acetylcholinesterase associated with pirimicarb and organophosphorous insecticide resistance in the cotton aphid, Aphis gossypii Glover (Homoptera: Aphididae).
  Insect Mol Biol, 13, 549-553.  
12485766 H.Schulze, S.Vorlová, F.Villatte, T.T.Bachmann, and R.D.Schmid (2003).
Design of acetylcholinesterases for biosensor applications.
  Biosens Bioelectron, 18, 201-209.  
12838268 S.J.Teague (2003).
Implications of protein flexibility for drug discovery.
  Nat Rev Drug Discov, 2, 527-541.  
12601798 T.Zeev-Ben-Mordehai, I.Silman, and J.L.Sussman (2003).
Acetylcholinesterase in motion: visualizing conformational changes in crystal structures by a morphing procedure.
  Biopolymers, 68, 395-406.  
12147513 E.Devic, D.Li, A.Dauta, P.Henriksen, G.A.Codd, J.L.Marty, and D.Fournier (2002).
Detection of anatoxin-a(s) in environmental samples of cyanobacteria by using a biosensor with engineered acetylcholinesterases.
  Appl Environ Microbiol, 68, 4102-4106.  
12149129 I.Fremaux, S.Mazères, A.Brisson-Lougarre, M.Arnaud, C.Ladurantie, and D.Fournier (2002).
Improvement of Drosophila acetylcholinesterase stability by elimination of a free cysteine.
  BMC Biochem, 3, 21.  
  11942747 O.Kozaki, T.Shono, T.Tomita, D.Taylor, and Y.Kono (2002).
Linkage analysis of an acetylcholinesterase gene in the house fly Musca domestica (Diptera: Muscidae).
  J Econ Entomol, 95, 129-133.  
11170446 M.Golicnik, D.Fournier, and J.Stojan (2001).
Interaction of Drosophila acetylcholinesterases with D-tubocurarine: an explanation of the activation by an inhibitor.
  Biochemistry, 40, 1214-1219.  
11053835 G.Kryger, M.Harel, K.Giles, L.Toker, B.Velan, A.Lazar, C.Kronman, D.Barak, N.Ariel, A.Shafferman, I.Silman, and J.L.Sussman (2000).
Structures of recombinant native and E202Q mutant human acetylcholinesterase complexed with the snake-venom toxin fasciculin-II.
  Acta Crystallogr D Biol Crystallogr, 56, 1385-1394.
PDB codes: 1b41 1f8u
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB codes are shown on the right.