2CEK

Conformational Flexibility in the Peripheral Site of Torpedo californica Acetylcholinesterase Revealed by the Complex Structure with a Bifunctional Inhibitor

PDB DOI: https://doi.org/10.2210/pdb2CEK/pdb

Classification: HYDROLASE
Organism(s): Tetronarce californica
Mutation(s): No

Deposited: 2006-02-08 Released: 2006-04-10
Deposition Author(s): Sanson, B., Colletier, J.P., Nachon, F., Gabellieri, E., Fattorusso, C., Campiani, G., Weik, M.

Experimental Data Snapshot

Method: X-RAY DIFFRACTION
Resolution: 2.20 ?
R-Value Free: 0.206
R-Value Work: 0.175
R-Value Observed: 0.175

Starting Model: experimental
View more details

wwPDB Validation 3D Report Full Report

Ligand Structure Quality Assessment

This is version 3.3 of the entry. See complete history.

Literature

Conformational flexibility in the peripheral site of Torpedo californica acetylcholinesterase revealed by the complex structure with a bifunctional inhibitor.

Colletier, J.P., Sanson, B., Nachon, F., Gabellieri, E., Fattorusso, C., Campiani, G., Weik, M.

(2006) J Am Chem Soc 128: 4526-4527

PubMed: 16594661 Search on PubMed
DOI: https://doi.org/10.1021/ja058683b
Primary Citation of Related Structures:
2CEK

PubMed Abstract:
The X-ray crystallographic structure of Torpedo californica acetylcholinesterase (TcAChE) in complex with the bifunctional inhibitor NF595, a potentially new anti-Alzheimer drug, has been solved. For the first time in TcAChE, a major conformational change in the peripheral-site tryptophan residue is observed upon complexation. The observed conformational flexibility highlights the dynamic nature of protein structures and is of importance for structure-based drug design.

Organizational Affiliation

Laboratoire de Biophysique Moléculaire, Institut de Biologie Structurale, 38027 Grenoble, France.

Macromolecule Content

Total Structure Weight: 62.94 kDa
Atom Count: 5,162
Modelled Residue Count: 532
Deposited Residue Count: 535
Unique protein chains: 1

Macromolecules

Find similar proteins by:

(by identity cutoff) | 3D Structure

Entity ID: 1
Molecule	Chains	Sequence Length	Organism	Details	Image
ACETYLCHOLINESTERASE	A	535	Tetronarce californica	Mutation(s): 0 EC: 3.1.1.7
UniProt
Find proteins for P04058 (Tetronarce californica) Explore P04058 Go to UniProtKB: P04058
Entity Groups
Sequence Clusters	30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt Group	P04058
Glycosylation
Glycosylation Sites: 3	Glycosylation Focus chain A
Sequence Annotations Expand
Reference Sequence

Oligosaccharides

Help

Entity ID: 2
Molecule	Chains	Length	2D Diagram	Glycosylation	3D Interactions
2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose	B	2		N-Glycosylation	Interactions Focus chain B Interactions & Density Focus chain B
Glycosylation Resources
GlyTouCan: G42666HT GlyCosmos: G42666HT GlyGen: G42666HT

Small Molecules

Ligands 4 Unique
ID	Chains	Name / Formula / InChI Key	2D Diagram	3D Interactions
N8T Query on N8T Download Ideal Coordinates CCD File SDF format, chain E [auth A] MOL2 format, chain E [auth A] mmCIF format, chain E [auth A]	E [auth A]	N-[8-(1,2,3,4-TETRAHYDROACRIDIN-9-YLTHIO)OCTYL]-1,2,3,4-TETRAHYDROACRIDIN-9-AMINE C₃₄ H₄₁ N₃ S COEYCPFFRLYNSC-UHFFFAOYSA-N		Interactions Focus chain E [auth A] Interactions & Density Focus chain E [auth A]
NAG Query on NAG Download Ideal Coordinates CCD File SDF format, chain C [auth A] SDF format, chain D [auth A] MOL2 format, chain C [auth A] MOL2 format, chain D [auth A] mmCIF format, chain C [auth A] mmCIF format, chain D [auth A]	C [auth A], D [auth A]	2-acetamido-2-deoxy-beta-D-glucopyranose C₈ H₁₅ N O₆ OVRNDRQMDRJTHS-FMDGEEDCSA-N		Interactions Focus chain C [auth A] Focus chain D [auth A] Interactions & Density Focus chain C [auth A] Focus chain D [auth A]
MES Query on MES Download Ideal Coordinates CCD File SDF format, chain G [auth A] SDF format, chain F [auth A] MOL2 format, chain G [auth A] MOL2 format, chain F [auth A] mmCIF format, chain G [auth A] mmCIF format, chain F [auth A]	F [auth A], G [auth A]	2-(N-MORPHOLINO)-ETHANESULFONIC ACID C₆ H₁₃ N O₄ S SXGZJKUKBWWHRA-UHFFFAOYSA-N		Interactions Focus chain F [auth A] Focus chain G [auth A] Interactions & Density Focus chain F [auth A] Focus chain G [auth A]
PGE Query on PGE Download Ideal Coordinates CCD File SDF format, chain H [auth A] SDF format, chain I [auth A] SDF format, chain J [auth A] SDF format, chain K [auth A] MOL2 format, chain H [auth A] MOL2 format, chain I [auth A] MOL2 format, chain J [auth A] MOL2 format, chain K [auth A] mmCIF format, chain H [auth A] mmCIF format, chain I [auth A] mmCIF format, chain J [auth A] mmCIF format, chain K [auth A]	H [auth A], I [auth A], J [auth A], K [auth A]	TRIETHYLENE GLYCOL C₆ H₁₄ O₄ ZIBGPFATKBEMQZ-UHFFFAOYSA-N		Interactions Focus chain H [auth A] Focus chain I [auth A] Focus chain J [auth A] Focus chain K [auth A] Interactions & Density Focus chain H [auth A] Focus chain I [auth A] Focus chain J [auth A] Focus chain K [auth A]

Experimental Data & Validation

Experimental Data

Method: X-RAY DIFFRACTION
Resolution: 2.20 ?
R-Value Free: 0.206
R-Value Work: 0.175
R-Value Observed: 0.175
Space Group: P 3₁ 2 1

Unit Cell:

Length ( ? )	Angle ( ? )
a = 111.94	α = 90
b = 111.94	β = 90
c = 137.12	γ = 120

Software Package:

Software Name	Purpose
CNS	refinement
XDS	data reduction
XSCALE	data scaling
CNS	phasing

Structure Validation

View Full Validation Report

Ligand Structure Quality Assessment

Entry History

Deposition Data

Released Date: 2006-04-10

Deposition Author(s):

Revision History (Full details and data files)

Version 1.0: 2006-04-10
Type: Initial release
Version 1.1: 2011-05-08
Changes: Version format compliance
Version 1.2: 2011-07-13
Changes: Version format compliance
Version 2.0: 2018-07-25
Changes: Advisory, Atomic model, Data collection, Database references, Derived calculations, Non-polymer description, Structure summary
Version 2.1: 2019-05-08
Changes: Data collection, Derived calculations, Experimental preparation
Version 3.0: 2020-07-29
Type: Remediation
Reason: Carbohydrate remediation
Changes: Atomic model, Data collection, Derived calculations, Other, Structure summary
Version 3.1: 2021-05-12
Changes: Derived calculations, Structure summary
Version 3.2: 2023-12-13
Changes: Data collection, Database references, Refinement description
Version 3.3: 2024-10-16
Changes: Structure summary