8AEN

Human acetylcholinesterase in complex with zinc and N,N,N-trimethyl-2-oxo-2-(2-(pyridin-2-ylmethylene)hydrazineyl)ethan-1-aminium

PDB DOI: https://doi.org/10.2210/pdb8AEN/pdb

Classification: HYDROLASE
Organism(s): Homo sapiens
Expression System: Cricetulus griseus
Mutation(s): No

Deposited: 2022-07-13 Released: 2023-06-21
Deposition Author(s): Nachon, F., Dias, J., Brazzolotto, X.
Funding Organization(s): French Ministry of Armed Forces

Experimental Data Snapshot

Method: X-RAY DIFFRACTION
Resolution: 3.01 Å
R-Value Free: 0.196
R-Value Work: 0.162
R-Value Observed: 0.164

Starting Model: experimental
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wwPDB Validation 3D Report Full Report

Ligand Structure Quality Assessment

This is version 1.1 of the entry. See complete history.

Literature

Grid-Type Quaternary Metallosupramolecular Compounds Inhibit Human Cholinesterases through Dynamic Multivalent Interactions.

Nachon, F., Brazzolotto, X., Dias, J., Courageux, C., Drozdz, W., Cao, X.Y., Stefankiewicz, A.R., Lehn, J.M.

(2022) Chembiochem 23: e202200456-e202200456

PubMed: 36193860 Search on PubMed
DOI: https://doi.org/10.1002/cbic.202200456
Primary Citation of Related Structures:
8AEN, 8AEV, 8AM1, 8AM2

PubMed Abstract:
We report the implementation of coordination complexes containing two types of cationic moieties, i. e. pyridinium and ammonium quaternary salt, as potential inhibitors of human cholinesterase enzymes. Utilization of ligands containing NNO-coordination site and binding zinc metal ion allowed mono- and tetra-nuclear complexes to be obtained with corner and grid structural type, respectively, thus affecting the overall charge of the compounds (from +1 to +8). We were able to examine for the first time the multivalency effect of metallosupramolecular species on their inhibitory abilities towards acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). Importantly, resolution of the crystal structures of the obtained enzyme-substrate complexes provided a better understanding of the inhibition process at the molecular level.

Organizational Affiliation

Département de Toxicologie et Risques Chimiques, Institut de Recherche Biomédicale des Armées, 1 place Gal Valérie André, BP87, 91220, Brétigny-sur-Orge, France.

Macromolecule Content

Total Structure Weight: 125.68 kDa
Atom Count: 8,794
Modelled Residue Count: 1,068
Deposited Residue Count: 1,086
Unique protein chains: 1

Macromolecules

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(by identity cutoff) | 3D Structure

Entity ID: 1
Molecule	Chains	Sequence Length	Organism	Details	Image
Acetylcholinesterase	A, B	543	Homo sapiens	Mutation(s): 0 Gene Names: ACHE EC: 3.1.1.7
UniProt & NIH Common Fund Data Resources
Find proteins for P22303 (Homo sapiens) Explore P22303 Go to UniProtKB: P22303
PHAROS: P22303 GTEx: ENSG00000087085
Entity Groups
Sequence Clusters	30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt Group	P22303
Glycosylation
Glycosylation Sites: 1	Glycosylation Focus chain A Focus chain B	Go to GlyGen: P22303-1
Sequence Annotations Expand
Reference Sequence

Oligosaccharides

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Entity ID: 2
Molecule	Chains	Length	2D Diagram	Glycosylation	3D Interactions
2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-[alpha-L-fucopyranose-(1-6)]2-acetamido-2-deoxy-beta-D-glucopyranose	C, F	3		N-Glycosylation	Interactions Focus chain C Focus chain F Interactions & Density Focus chain C Focus chain F
Glycosylation Resources
GlyTouCan: G21290RB GlyCosmos: G21290RB GlyGen: G21290RB

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

Entity ID: 4
Molecule	Chains	Length	2D Diagram	Glycosylation	3D Interactions
N-acetyl-alpha-neuraminic acid-(2-3)-beta-D-galactopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose	E	3		N/A	Interactions Focus chain E Interactions & Density Focus chain E
Glycosylation Resources
GlyTouCan: G00065MO GlyCosmos: G00065MO GlyGen: G00065MO

Small Molecules

Ligands 5 Unique
ID	Chains	Name / Formula / InChI Key	2D Diagram	3D Interactions
LWL (Subject of Investigation/LOI) Query on LWL Download Ideal Coordinates CCD File SDF format, chain G [auth A] SDF format, chain RA [auth B] MOL2 format, chain G [auth A] MOL2 format, chain RA [auth B] mmCIF format, chain G [auth A] mmCIF format, chain RA [auth B]	G [auth A], RA [auth B]	N,N,N-trimethyl-2-oxo-2-(2-(pyridin-2-ylmethylene)hydrazineyl)ethan-1-aminium C₁₁ H₁₇ N₄ O DQSNXLQZLFKDAM-UHFFFAOYSA-O		Interactions Focus chain G [auth A] Focus chain RA [auth B] Interactions & Density Focus chain G [auth A] Focus chain RA [auth B]
SO4 Query on SO4 Download Ideal Coordinates CCD File SDF format, chain AB [auth B] SDF format, chain BB [auth B] SDF format, chain CB [auth B] SDF format, chain I [auth A] SDF format, chain J [auth A] SDF format, chain K [auth A] SDF format, chain L [auth A] SDF format, chain M [auth A] SDF format, chain N [auth A] SDF format, chain O [auth A] SDF format, chain P [auth A] SDF format, chain Q [auth A] SDF format, chain R [auth A] SDF format, chain S [auth A] SDF format, chain TA [auth B] SDF format, chain UA [auth B] SDF format, chain VA [auth B] SDF format, chain WA [auth B] SDF format, chain XA [auth B] SDF format, chain YA [auth B] SDF format, chain ZA [auth B] MOL2 format, chain AB [auth B] MOL2 format, chain BB [auth B] MOL2 format, chain CB [auth B] MOL2 format, chain I [auth A] MOL2 format, chain J [auth A] MOL2 format, chain K [auth A] MOL2 format, chain L [auth A] MOL2 format, chain M [auth A] MOL2 format, chain N [auth A] MOL2 format, chain O [auth A] MOL2 format, chain P [auth A] MOL2 format, chain Q [auth A] MOL2 format, chain R [auth A] MOL2 format, chain S [auth A] MOL2 format, chain TA [auth B] MOL2 format, chain UA [auth B] MOL2 format, chain VA [auth B] MOL2 format, chain WA [auth B] MOL2 format, chain XA [auth B] MOL2 format, chain YA [auth B] MOL2 format, chain ZA [auth B] mmCIF format, chain AB [auth B] mmCIF format, chain BB [auth B] mmCIF format, chain CB [auth B] mmCIF format, chain I [auth A] mmCIF format, chain J [auth A] mmCIF format, chain K [auth A] mmCIF format, chain L [auth A] mmCIF format, chain M [auth A] mmCIF format, chain N [auth A] mmCIF format, chain O [auth A] mmCIF format, chain P [auth A] mmCIF format, chain Q [auth A] mmCIF format, chain R [auth A] mmCIF format, chain S [auth A] mmCIF format, chain TA [auth B] mmCIF format, chain UA [auth B] mmCIF format, chain VA [auth B] mmCIF format, chain WA [auth B] mmCIF format, chain XA [auth B] mmCIF format, chain YA [auth B] mmCIF format, chain ZA [auth B]	AB [auth B] BB [auth B] CB [auth B] I [auth A] J [auth A] AB [auth B], BB [auth B], CB [auth B], I [auth A], J [auth A], K [auth A], L [auth A], M [auth A], N [auth A], O [auth A], P [auth A], Q [auth A], R [auth A], S [auth A], TA [auth B], UA [auth B], VA [auth B], WA [auth B], XA [auth B], YA [auth B], ZA [auth B]	SULFATE ION O₄ S QAOWNCQODCNURD-UHFFFAOYSA-L		Interactions Focus chain AB [auth B] Focus chain BB [auth B] Focus chain CB [auth B] Focus chain I [auth A] Focus chain J [auth A] Focus chain K [auth A] Focus chain L [auth A] Focus chain M [auth A] Focus chain N [auth A] Focus chain O [auth A] Focus chain P [auth A] Focus chain Q [auth A] Focus chain R [auth A] Focus chain S [auth A] Focus chain TA [auth B] Focus chain UA [auth B] Focus chain VA [auth B] Focus chain WA [auth B] Focus chain XA [auth B] Focus chain YA [auth B] Focus chain ZA [auth B] Interactions & Density Focus chain AB [auth B] Focus chain BB [auth B] Focus chain CB [auth B] Focus chain I [auth A] Focus chain J [auth A] Focus chain K [auth A] Focus chain L [auth A] Focus chain M [auth A] Focus chain N [auth A] Focus chain O [auth A] Focus chain P [auth A] Focus chain Q [auth A] Focus chain R [auth A] Focus chain S [auth A] Focus chain TA [auth B] Focus chain UA [auth B] Focus chain VA [auth B] Focus chain WA [auth B] Focus chain XA [auth B] Focus chain YA [auth B] Focus chain ZA [auth B]
ZN (Subject of Investigation/LOI) Query on ZN Download Ideal Coordinates CCD File SDF format, chain H [auth A] SDF format, chain KA [auth A] SDF format, chain LA [auth A] SDF format, chain SA [auth B] MOL2 format, chain H [auth A] MOL2 format, chain KA [auth A] MOL2 format, chain LA [auth A] MOL2 format, chain SA [auth B] mmCIF format, chain H [auth A] mmCIF format, chain KA [auth A] mmCIF format, chain LA [auth A] mmCIF format, chain SA [auth B]	H [auth A], KA [auth A], LA [auth A], SA [auth B]	ZINC ION Zn PTFCDOFLOPIGGS-UHFFFAOYSA-N		Interactions Focus chain H [auth A] Focus chain KA [auth A] Focus chain LA [auth A] Focus chain SA [auth B] Interactions & Density Focus chain H [auth A] Focus chain KA [auth A] Focus chain LA [auth A] Focus chain SA [auth B]
CL Query on CL Download Ideal Coordinates CCD File SDF format, chain AA [auth A] SDF format, chain BA [auth A] SDF format, chain CA [auth A] SDF format, chain DA [auth A] SDF format, chain DB [auth B] SDF format, chain EA [auth A] SDF format, chain EB [auth B] SDF format, chain FA [auth A] SDF format, chain FB [auth B] SDF format, chain GA [auth A] SDF format, chain GB [auth B] SDF format, chain HA [auth A] SDF format, chain HB [auth B] SDF format, chain IA [auth A] SDF format, chain IB [auth B] SDF format, chain JA [auth A] SDF format, chain JB [auth B] SDF format, chain KB [auth B] SDF format, chain LB [auth B] SDF format, chain MB [auth B] SDF format, chain NB [auth B] SDF format, chain OB [auth B] SDF format, chain PB [auth B] SDF format, chain QB [auth B] SDF format, chain RB [auth B] SDF format, chain SB [auth B] SDF format, chain T [auth A] SDF format, chain TB [auth B] SDF format, chain U [auth A] SDF format, chain UB [auth B] SDF format, chain V [auth A] SDF format, chain VB [auth B] SDF format, chain W [auth A] SDF format, chain X [auth A] SDF format, chain Y [auth A] SDF format, chain Z [auth A] MOL2 format, chain AA [auth A] MOL2 format, chain BA [auth A] MOL2 format, chain CA [auth A] MOL2 format, chain DA [auth A] MOL2 format, chain DB [auth B] MOL2 format, chain EA [auth A] MOL2 format, chain EB [auth B] MOL2 format, chain FA [auth A] MOL2 format, chain FB [auth B] MOL2 format, chain GA [auth A] MOL2 format, chain GB [auth B] MOL2 format, chain HA [auth A] MOL2 format, chain HB [auth B] MOL2 format, chain IA [auth A] MOL2 format, chain IB [auth B] MOL2 format, chain JA [auth A] MOL2 format, chain JB [auth B] MOL2 format, chain KB [auth B] MOL2 format, chain LB [auth B] MOL2 format, chain MB [auth B] MOL2 format, chain NB [auth B] MOL2 format, chain OB [auth B] MOL2 format, chain PB [auth B] MOL2 format, chain QB [auth B] MOL2 format, chain RB [auth B] MOL2 format, chain SB [auth B] MOL2 format, chain T [auth A] MOL2 format, chain TB [auth B] MOL2 format, chain U [auth A] MOL2 format, chain UB [auth B] MOL2 format, chain V [auth A] MOL2 format, chain VB [auth B] MOL2 format, chain W [auth A] MOL2 format, chain X [auth A] MOL2 format, chain Y [auth A] MOL2 format, chain Z [auth A] mmCIF format, chain AA [auth A] mmCIF format, chain BA [auth A] mmCIF format, chain CA [auth A] mmCIF format, chain DA [auth A] mmCIF format, chain DB [auth B] mmCIF format, chain EA [auth A] mmCIF format, chain EB [auth B] mmCIF format, chain FA [auth A] mmCIF format, chain FB [auth B] mmCIF format, chain GA [auth A] mmCIF format, chain GB [auth B] mmCIF format, chain HA [auth A] mmCIF format, chain HB [auth B] mmCIF format, chain IA [auth A] mmCIF format, chain IB [auth B] mmCIF format, chain JA [auth A] mmCIF format, chain JB [auth B] mmCIF format, chain KB [auth B] mmCIF format, chain LB [auth B] mmCIF format, chain MB [auth B] mmCIF format, chain NB [auth B] mmCIF format, chain OB [auth B] mmCIF format, chain PB [auth B] mmCIF format, chain QB [auth B] mmCIF format, chain RB [auth B] mmCIF format, chain SB [auth B] mmCIF format, chain T [auth A] mmCIF format, chain TB [auth B] mmCIF format, chain U [auth A] mmCIF format, chain UB [auth B] mmCIF format, chain V [auth A] mmCIF format, chain VB [auth B] mmCIF format, chain W [auth A] mmCIF format, chain X [auth A] mmCIF format, chain Y [auth A] mmCIF format, chain Z [auth A]	AA [auth A] BA [auth A] CA [auth A] DA [auth A] DB [auth B] AA [auth A], BA [auth A], CA [auth A], DA [auth A], DB [auth B], EA [auth A], EB [auth B], FA [auth A], FB [auth B], GA [auth A], GB [auth B], HA [auth A], HB [auth B], IA [auth A], IB [auth B], JA [auth A], JB [auth B], KB [auth B], LB [auth B], MB [auth B], NB [auth B], OB [auth B], PB [auth B], QB [auth B], RB [auth B], SB [auth B], T [auth A], TB [auth B], U [auth A], UB [auth B], V [auth A], VB [auth B], W [auth A], X [auth A], Y [auth A], Z [auth A]	CHLORIDE ION Cl VEXZGXHMUGYJMC-UHFFFAOYSA-M		Interactions Focus chain AA [auth A] Focus chain BA [auth A] Focus chain CA [auth A] Focus chain DA [auth A] Focus chain DB [auth B] Focus chain EA [auth A] Focus chain EB [auth B] Focus chain FA [auth A] Focus chain FB [auth B] Focus chain GA [auth A] Focus chain GB [auth B] Focus chain HA [auth A] Focus chain HB [auth B] Focus chain IA [auth A] Focus chain IB [auth B] Focus chain JA [auth A] Focus chain JB [auth B] Focus chain KB [auth B] Focus chain LB [auth B] Focus chain MB [auth B] Focus chain NB [auth B] Focus chain OB [auth B] Focus chain PB [auth B] Focus chain QB [auth B] Focus chain RB [auth B] Focus chain SB [auth B] Focus chain T [auth A] Focus chain TB [auth B] Focus chain U [auth A] Focus chain UB [auth B] Focus chain V [auth A] Focus chain VB [auth B] Focus chain W [auth A] Focus chain X [auth A] Focus chain Y [auth A] Focus chain Z [auth A] Interactions & Density Focus chain AA [auth A] Focus chain BA [auth A] Focus chain CA [auth A] Focus chain DA [auth A] Focus chain DB [auth B] Focus chain EA [auth A] Focus chain EB [auth B] Focus chain FA [auth A] Focus chain FB [auth B] Focus chain GA [auth A] Focus chain GB [auth B] Focus chain HA [auth A] Focus chain HB [auth B] Focus chain IA [auth A] Focus chain IB [auth B] Focus chain JA [auth A] Focus chain JB [auth B] Focus chain KB [auth B] Focus chain LB [auth B] Focus chain MB [auth B] Focus chain NB [auth B] Focus chain OB [auth B] Focus chain PB [auth B] Focus chain QB [auth B] Focus chain RB [auth B] Focus chain SB [auth B] Focus chain T [auth A] Focus chain TB [auth B] Focus chain U [auth A] Focus chain UB [auth B] Focus chain V [auth A] Focus chain VB [auth B] Focus chain W [auth A] Focus chain X [auth A] Focus chain Y [auth A] Focus chain Z [auth A]
MG Query on MG Download Ideal Coordinates CCD File SDF format, chain AC [auth B] SDF format, chain BC [auth B] SDF format, chain CC [auth B] SDF format, chain MA [auth A] SDF format, chain NA [auth A] SDF format, chain OA [auth A] SDF format, chain PA [auth A] SDF format, chain QA [auth A] SDF format, chain WB [auth B] SDF format, chain XB [auth B] SDF format, chain YB [auth B] SDF format, chain ZB [auth B] MOL2 format, chain AC [auth B] MOL2 format, chain BC [auth B] MOL2 format, chain CC [auth B] MOL2 format, chain MA [auth A] MOL2 format, chain NA [auth A] MOL2 format, chain OA [auth A] MOL2 format, chain PA [auth A] MOL2 format, chain QA [auth A] MOL2 format, chain WB [auth B] MOL2 format, chain XB [auth B] MOL2 format, chain YB [auth B] MOL2 format, chain ZB [auth B] mmCIF format, chain AC [auth B] mmCIF format, chain BC [auth B] mmCIF format, chain CC [auth B] mmCIF format, chain MA [auth A] mmCIF format, chain NA [auth A] mmCIF format, chain OA [auth A] mmCIF format, chain PA [auth A] mmCIF format, chain QA [auth A] mmCIF format, chain WB [auth B] mmCIF format, chain XB [auth B] mmCIF format, chain YB [auth B] mmCIF format, chain ZB [auth B]	AC [auth B] BC [auth B] CC [auth B] MA [auth A] NA [auth A] AC [auth B], BC [auth B], CC [auth B], MA [auth A], NA [auth A], OA [auth A], PA [auth A], QA [auth A], WB [auth B], XB [auth B], YB [auth B], ZB [auth B]	MAGNESIUM ION Mg JLVVSXFLKOJNIY-UHFFFAOYSA-N		Interactions Focus chain AC [auth B] Focus chain BC [auth B] Focus chain CC [auth B] Focus chain MA [auth A] Focus chain NA [auth A] Focus chain OA [auth A] Focus chain PA [auth A] Focus chain QA [auth A] Focus chain WB [auth B] Focus chain XB [auth B] Focus chain YB [auth B] Focus chain ZB [auth B] Interactions & Density Focus chain AC [auth B] Focus chain BC [auth B] Focus chain CC [auth B] Focus chain MA [auth A] Focus chain NA [auth A] Focus chain OA [auth A] Focus chain PA [auth A] Focus chain QA [auth A] Focus chain WB [auth B] Focus chain XB [auth B] Focus chain YB [auth B] Focus chain ZB [auth B]