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PDBsum entry 1vzj
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protein Protein-protein interface(s) links
Hydrolase PDB id
1vzj

 

 

 

 

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Contents
Protein chains
26 a.a. *
31 a.a. *
32 a.a. *
27 a.a. *
34 a.a. *
15 a.a. *
Waters ×39
* Residue conservation analysis
PDB id:
1vzj
Name: Hydrolase
Title: Structure of the tetramerization domain of acetylcholinesterase: four- fold interaction of a www motif with a left-handed polyproline helix
Structure: Acetylcholinesterase. Chain: a, b, c, d, e, f, g, h. Fragment: c terminal tetramerization domain, residues 575-614. Synonym: acetylcholinesterase collagenic tail peptide (wat). Engineered: yes. Other_details: wat chains a-d interact with prad chain i while wat chains e-h interact with prad chain j. Acetylcholinesterase collagenic tail peptide. Chain: i, j.
Source: Synthetic: yes. Homo sapiens. Human. Organism_taxid: 9606. Other_details: the human ache sequence of wat was modified at two positions, 21 and 37, to replace met and cys by mse and ser, respectively. Organism_taxid: 9606
Biol. unit: Pentamer (from PDB file)
Resolution:
2.35Å     R-factor:   0.247     R-free:   0.259
Authors: H.Dvir,M.Harel,S.Bon,W.-Q.Liu,M.Vidal,C.Garbay,J.L.Sussman, J.Massoulie,I.Silman
Key ref:
H.Dvir et al. (2004). The synaptic acetylcholinesterase tetramer assembles around a polyproline II helix. EMBO J, 23, 4394-4405. PubMed id: 15526038 DOI: 10.1038/sj.emboj.7600425
Date:
20-May-04     Release date:   10-Jan-05    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P22303  (ACES_HUMAN) -  Acetylcholinesterase from Homo sapiens
Seq:
Struc: 		 
Seq:
Struc: 		614 a.a.
26 a.a.
Protein chain
Pfam   ArchSchema ?
P22303  (ACES_HUMAN) -  Acetylcholinesterase from Homo sapiens
Seq:
Struc: 		 
Seq:
Struc: 		614 a.a.
31 a.a.
Protein chains
Pfam   ArchSchema ?
P22303  (ACES_HUMAN) -  Acetylcholinesterase from Homo sapiens
Seq:
Struc: 		 
Seq:
Struc: 		614 a.a.
32 a.a.
Protein chain
Pfam   ArchSchema ?
P22303  (ACES_HUMAN) -  Acetylcholinesterase from Homo sapiens
Seq:
Struc: 		 
Seq:
Struc: 		614 a.a.
27 a.a.
Protein chains
Pfam   ArchSchema ?
P22303  (ACES_HUMAN) -  Acetylcholinesterase from Homo sapiens
Seq:
Struc: 		 
Seq:
Struc: 		614 a.a.
34 a.a.
Protein chains
Pfam   ArchSchema ?
Q9Y215  (COLQ_HUMAN) -  Acetylcholinesterase collagenic tail peptide from Homo sapiens
Seq:
Struc: 		455 a.a.
15 a.a.
Key:    PfamA domain  Secondary structure

 Enzyme reactions 
   Enzyme class: Chains A, B, C, D, E, F, G, H: E.C.3.1.1.7  - acetylcholinesterase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: acetylcholine + H2O = choline + acetate + H+
acetylcholine
 + H2O
 = choline
 + acetate
 + H(+)
Molecule diagrams generated from .mol files obtained from the KEGG ftp site

 

 
    reference    
 
 
DOI no: 10.1038/sj.emboj.7600425 EMBO J 23:4394-4405 (2004)
PubMed id: 15526038  
 
 
The synaptic acetylcholinesterase tetramer assembles around a polyproline II helix.
H.Dvir, M.Harel, S.Bon, W.Q.Liu, M.Vidal, C.Garbay, J.L.Sussman, J.Massoulié, I.Silman.
 
  ABSTRACT  
 
Functional localization of acetylcholinesterase (AChE) in vertebrate muscle and brain depends on interaction of the tryptophan amphiphilic tetramerization (WAT) sequence, at the C-terminus of its major splice variant (T), with a proline-rich attachment domain (PRAD), of the anchoring proteins, collagenous (ColQ) and proline-rich membrane anchor. The crystal structure of the WAT/PRAD complex reveals a novel supercoil structure in which four parallel WAT chains form a left-handed superhelix around an antiparallel left-handed PRAD helix resembling polyproline II. The WAT coiled coils possess a WWW motif making repetitive hydrophobic stacking and hydrogen-bond interactions with the PRAD. The WAT chains are related by an approximately 4-fold screw axis around the PRAD. Each WAT makes similar but unique interactions, consistent with an asymmetric pattern of disulfide linkages between the AChE tetramer subunits and ColQ. The P59Q mutation in ColQ, which causes congenital endplate AChE deficiency, and is located within the PRAD, disrupts crucial WAT-WAT and WAT-PRAD interactions. A model is proposed for the synaptic AChE(T) tetramer.
 
  Selected figure(s)  
 
Figure 1.
Figure 1 Schematic representations of AChE tetramers. (A) Modes of assembly of AChE subunits into tetramers. (B) Orientations of the polypeptide chains and arrangement of disulfide bonds in the [AChE[T]][4]ColQ complex deduced by site-directed mutagenesis. 		Figure 7.
Figure 7 Stacking interactions between the WAT and PRAD helices. Side view of the complex, with the superhelical axis running vertically, and PRAD depicted as a stick model. Only the Trps of WAT are shown, in space-filling format, with those of each WAT chain colored individually. The Trp side chains form a spiral staircase around the PRAD, fitting into grooves formed by the extended left-handed PRAD helix.
 
  The above figures are reprinted from an Open Access publication published by Macmillan Publishers Ltd: EMBO J (2004, 23, 4394-4405) copyright 2004.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
20203414 P.Anglade, and Y.Larabi-Godinot (2010).
Historical landmarks in the histochemistry of the cholinergic synapse: Perspectives for future researches.
  Biomed Res, 31, 1.  
20356043 R.Vijayan, and P.C.Biggin (2010).
Conformational preferences of a 14-residue fibrillogenic peptide from acetylcholinesterase.
  Biochemistry, 49, 3678-3684.  
19651048 A.A.Gorfe, B.Lu, Z.Yu, and J.A.McCammon (2009).
Enzymatic activity versus structural dynamics: the case of acetylcholinesterase tetramer.
  Biophys J, 97, 897-905.  
19019080 D.Liang, J.P.Blouet, F.Borrega, S.Bon, and J.Massoulié (2009).
Respective roles of the catalytic domains and C-terminal tail peptides in the oligomerization and secretory trafficking of human acetylcholinesterase and butyrylcholinesterase.
  FEBS J, 276, 94.  
19383604 E.Podoly, D.E.Shalev, S.Shenhar-Tsarfaty, E.R.Bennett, E.Ben Assayag, H.Wilgus, O.Livnah, and H.Soreq (2009).
The Butyrylcholinesterase K Variant Confers Structurally Derived Risks for Alzheimer Pathology{diamondsuit}.
  J Biol Chem, 284, 17170-17179.  
19490106 K.W.Leung, H.Q.Xie, V.P.Chen, M.K.Mok, G.K.Chu, R.C.Choi, and K.W.Tsim (2009).
Restricted localization of proline-rich membrane anchor (PRiMA) of globular form acetylcholinesterase at the neuromuscular junctions--contribution and expression from motor neurons.
  FEBS J, 276, 3031-3042.  
19402731 Y.Pan, J.L.Muzyka, and C.G.Zhan (2009).
Model of human butyrylcholinesterase tetramer by homology modeling and dynamics simulation.
  J Phys Chem B, 113, 6543-6552.  
17921202 A.A.Gorfe, C.E.Chang, I.Ivanov, and J.A.McCammon (2008).
Dynamics of the acetylcholinesterase tetramer.
  Biophys J, 94, 1144-1154.  
18279391 A.Frederick, I.Tsigelny, F.Cohenour, C.Spiker, E.Krejci, A.Chatonnet, S.Bourgoin, G.Richards, T.Allen, M.H.Whitlock, and L.Pezzementi (2008).
Acetylcholinesterase from the invertebrate Ciona intestinalis is capable of assembling into asymmetric forms when co-expressed with vertebrate collagenic tail peptide.
  FEBS J, 275, 1309-1322.  
18511416 H.Noureddine, S.Carvalho, C.Schmitt, J.Massoulié, and S.Bon (2008).
Acetylcholinesterase associates differently with its anchoring proteins ColQ and PRiMA.
  J Biol Chem, 283, 20722-20732.  
18313329 M.Guerra, A.Dobbertin, and C.Legay (2008).
Identification of cis-acting elements involved in acetylcholinesterase RNA alternative splicing.
  Mol Cell Neurosci, 38, 1.  
17476278 C.Perry, M.Pick, E.Podoly, A.Gilboa-Geffen, G.Zimmerman, E.H.Sklan, Y.Ben-Shaul, S.Diamant, and H.Soreq (2007).
Acetylcholinesterase/C terminal binding protein interactions modify Ikaros functions, causing T lymphopenia.
  Leukemia, 21, 1472-1480.  
17158452 H.Noureddine, C.Schmitt, W.Liu, C.Garbay, J.Massoulié, and S.Bon (2007).
Assembly of acetylcholinesterase tetramers by peptidic motifs from the proline-rich membrane anchor, PRiMA: competition between degradation and secretion pathways of heteromeric complexes.
  J Biol Chem, 282, 3487-3497.  
17324938 H.Q.Xie, R.C.Choi, K.W.Leung, N.L.Siow, L.W.Kong, F.T.Lau, H.B.Peng, and K.W.Tsim (2007).
Regulation of a transcript encoding the proline-rich membrane anchor of globular muscle acetylcholinesterase. The suppressive roles of myogenesis and innervating nerves.
  J Biol Chem, 282, 11765-11775.  
17653279 L.Jean, B.Thomas, A.Tahiri-Alaoui, M.Shaw, and D.J.Vaux (2007).
Heterologous amyloid seeding: revisiting the role of acetylcholinesterase in Alzheimer's disease.
  PLoS ONE, 2, e652.  
  17768338 M.N.Ngamelue, K.Homma, O.Lockridge, and O.A.Asojo (2007).
Crystallization and X-ray structure of full-length recombinant human butyrylcholinesterase.
  Acta Crystallogr Sect F Struct Biol Cryst Commun, 63, 723-727.
PDB code: 2pm8
16731619 S.Diamant, E.Podoly, A.Friedler, H.Ligumsky, O.Livnah, and H.Soreq (2006).
Butyrylcholinesterase attenuates amyloid fibril formation in vitro.
  Proc Natl Acad Sci U S A, 103, 8628-8633.  
16299589 D.Zhang, and J.A.McCammon (2005).
The association of tetrameric acetylcholinesterase with ColQ tail: a block normal mode analysis.
  PLoS Comput Biol, 1, e62.  
15626705 D.Zhang, J.Suen, Y.Zhang, Y.Song, Z.Radic, P.Taylor, M.J.Holst, C.Bajaj, N.A.Baker, and J.A.McCammon (2005).
Tetrameric mouse acetylcholinesterase: continuum diffusion rate calculations by solving the steady-state Smoluchowski equation using finite element methods.
  Biophys J, 88, 1659-1665.  
  16569291 M.E.Selkirk, O.Lazari, and J.B.Matthews (2005).
Functional genomics of nematode acetylcholinesterases.
  Parasitology, 131, S3-18.  
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 code is shown on the right.

 

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