spacer
spacer

PDBsum entry 1w6r

Go to PDB code: 
protein ligands metals links
Hydrolase PDB id
1w6r
Jmol
Contents
Protein chain
528 a.a. *
Ligands
NAG ×2
GNT
Metals
_MG
Waters ×246
* Residue conservation analysis
PDB id:
1w6r
Name: Hydrolase
Title: Complex of tcache with galanthamine derivative
Structure: Acetylcholinesterase. Chain: a. Fragment: residues 22-564. Synonym: ache. Ec: 3.1.1.7
Source: Torpedo californica. Pacific electric ray. Organism_taxid: 7787. Variant: g2 form. Organ: electric organ. Tissue: electroplaque
Resolution:
2.05Å     R-factor:   0.199     R-free:   0.232
Authors: H.M.Greenblatt,C.Guillou,D.Guenard,B.Badet,C.Thal,I.Silman, J.L.Sussman
Key ref: H.M.Greenblatt et al. (2004). The complex of a bivalent derivative of galanthamine with torpedo acetylcholinesterase displays drastic deformation of the active-site gorge: implications for structure-based drug design. J Am Chem Soc, 126, 15405-15411. PubMed id: 15563167 DOI: 10.1021/ja0466154
Date:
23-Aug-04     Release date:   25-Nov-04    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P04058  (ACES_TORCA) -  Acetylcholinesterase
Seq:
Struc:
 
Seq:
Struc:
586 a.a.
528 a.a.
Key:    PfamA 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   5 terms 
  Biological process     neurotransmitter catabolic process   2 terms 
  Biochemical function     hydrolase activity     3 terms  

 

 
    reference    
 
 
DOI no: 10.1021/ja0466154 J Am Chem Soc 126:15405-15411 (2004)
PubMed id: 15563167  
 
 
The complex of a bivalent derivative of galanthamine with torpedo acetylcholinesterase displays drastic deformation of the active-site gorge: implications for structure-based drug design.
H.M.Greenblatt, C.Guillou, D.Guénard, A.Argaman, S.Botti, B.Badet, C.Thal, I.Silman, J.L.Sussman.
 
  ABSTRACT  
 
Bifunctional derivatives of the alkaloid galanthamine, designed to interact with both the active site of the enzyme acetylcholinesterase (AChE) and its peripheral cation binding site, have been assayed with Torpedo californica AChE (TcAChE), and the three-dimensional structures of their complexes with the enzyme have been solved by X-ray crystallography. Differences were noted between the IC(50) values obtained for TcAChE and those for Electrophorus electricus AChE. These differences are ascribed to sequence differences in one or two residues lining the active-site gorge of the enzyme. The binding of one of the inhibitors disrupts the native conformation of one wall of the gorge, formed by the loop Trp279-Phe290. It is proposed that flexibility of this loop may permit the binding of inhibitors such as galanthamine, which are too bulky to penetrate the narrow neck of the gorge formed by Tyr121 and Phe330 as seen in the crystal structure.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
18701720 J.P.Colletier, D.Bourgeois, B.Sanson, D.Fournier, J.L.Sussman, I.Silman, and M.Weik (2008).
Shoot-and-Trap: use of specific x-ray damage to study structural protein dynamics by temperature-controlled cryo-crystallography.
  Proc Natl Acad Sci U S A, 105, 11742-11747.
PDB codes: 2vja 2vjb 2vjc 2vjd 2vt6 2vt7
18007027 J.P.Colletier, A.Royant, A.Specht, B.Sanson, F.Nachon, P.Masson, G.Zaccai, J.L.Sussman, M.Goeldner, I.Silman, D.Bourgeois, and M.Weik (2007).
Use of a 'caged' analogue to study the traffic of choline within acetylcholinesterase by kinetic crystallography.
  Acta Crystallogr D Biol Crystallogr, 63, 1115-1128.
PDB codes: 2v96 2v97 2v98 2va9
17653364 Z.Jin (2007).
Amaryllidaceae and Sceletium alkaloids.
  Nat Prod Rep, 24, 886-905.  
17084612 D.A.Erlanson (2006).
Fragment-based lead discovery: a chemical update.
  Curr Opin Biotechnol, 17, 643-652.  
16791318 G.Pastorin, S.Marchesan, J.Hoebeke, T.Da Ros, L.Ehret-Sabatier, J.P.Briand, M.Prato, and A.Bianco (2006).
Design and activity of cationic fullerene derivatives as inhibitors of acetylcholinesterase.
  Org Biomol Chem, 4, 2556-2562.  
16341717 L.Alisaraie, and G.Fels (2006).
Molecular docking study on the "back door" hypothesis for product clearance in acetylcholinesterase.
  J Mol Model, 12, 348-354.  
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.