8AEV

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

PDB DOI: https://doi.org/10.2210/pdb8AEV/pdb

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

Deposited: 2022-07-13 Released: 2023-06-14
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: 2.89 ?
R-Value Free: 0.207
R-Value Work: 0.184
R-Value Observed: 0.185

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: 124.98 kDa
Atom Count: 8,809
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: 2	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	E	2		N/A	Interactions Focus chain E Interactions & Density Focus chain E
Glycosylation Resources
GlyTouCan: G30207PZ GlyCosmos: G30207PZ GlyGen: G30207PZ

Small Molecules

Ligands 5 Unique
ID	Chains	Name / Formula / InChI Key	2D Diagram	3D Interactions
LWU (Subject of Investigation/LOI) Query on LWU Download Ideal Coordinates CCD File SDF format, chain G [auth A] MOL2 format, chain G [auth A] mmCIF format, chain G [auth A]	G [auth A]	1-(2-(2-((6-(dihydroxymethyl)-2-phenylpyrimidin-4-yl)methylene)hydrazineyl)-2-oxoethyl)pyridin-1-ium C₁₉ H₂₀ N₅ O₃ JPVVLHGFGWJHHI-UHFFFAOYSA-O		Interactions Focus chain G [auth A] Interactions & Density Focus chain G [auth A]
SO4 Query on SO4 Download Ideal Coordinates CCD File 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 OA [auth B] SDF format, chain P [auth A] SDF format, chain PA [auth B] SDF format, chain QA [auth B] SDF format, chain RA [auth B] SDF format, chain SA [auth B] SDF format, chain TA [auth B] SDF format, chain UA [auth B] SDF format, chain H [auth A] 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 OA [auth B] MOL2 format, chain P [auth A] MOL2 format, chain PA [auth B] MOL2 format, chain QA [auth B] MOL2 format, chain RA [auth B] MOL2 format, chain SA [auth B] MOL2 format, chain TA [auth B] MOL2 format, chain UA [auth B] MOL2 format, chain H [auth A] 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 OA [auth B] mmCIF format, chain P [auth A] mmCIF format, chain PA [auth B] mmCIF format, chain QA [auth B] mmCIF format, chain RA [auth B] mmCIF format, chain SA [auth B] mmCIF format, chain TA [auth B] mmCIF format, chain UA [auth B] mmCIF format, chain H [auth A]	H [auth A] I [auth A] J [auth A] K [auth A] L [auth A] H [auth A], I [auth A], J [auth A], K [auth A], L [auth A], M [auth A], N [auth A], O [auth A], OA [auth B], P [auth A], PA [auth B], QA [auth B], RA [auth B], SA [auth B], TA [auth B], UA [auth B]	SULFATE ION O₄ S QAOWNCQODCNURD-UHFFFAOYSA-L		Interactions Focus chain H [auth A] 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 OA [auth B] Focus chain P [auth A] Focus chain PA [auth B] Focus chain QA [auth B] Focus chain RA [auth B] Focus chain SA [auth B] Focus chain TA [auth B] Focus chain UA [auth B] Interactions & Density Focus chain H [auth A] 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 OA [auth B] Focus chain P [auth A] Focus chain PA [auth B] Focus chain QA [auth B] Focus chain RA [auth B] Focus chain SA [auth B] Focus chain TA [auth B] Focus chain UA [auth B]
ZN Query on ZN Download Ideal Coordinates CCD File SDF format, chain EA [auth A] SDF format, chain FA [auth A] SDF format, chain MB [auth B] SDF format, chain NB [auth B] SDF format, chain OB [auth B] MOL2 format, chain EA [auth A] MOL2 format, chain FA [auth A] MOL2 format, chain MB [auth B] MOL2 format, chain NB [auth B] MOL2 format, chain OB [auth B] mmCIF format, chain EA [auth A] mmCIF format, chain FA [auth A] mmCIF format, chain MB [auth B] mmCIF format, chain NB [auth B] mmCIF format, chain OB [auth B]	EA [auth A], FA [auth A], MB [auth B], NB [auth B], OB [auth B]	ZINC ION Zn PTFCDOFLOPIGGS-UHFFFAOYSA-N		Interactions Focus chain EA [auth A] Focus chain FA [auth A] Focus chain MB [auth B] Focus chain NB [auth B] Focus chain OB [auth B] Interactions & Density Focus chain EA [auth A] Focus chain FA [auth A] Focus chain MB [auth B] Focus chain NB [auth B] Focus chain OB [auth B]
CL Query on CL Download Ideal Coordinates CCD File SDF format, chain AA [auth A] SDF format, chain AB [auth B] SDF format, chain BA [auth A] SDF format, chain BB [auth B] SDF format, chain CB [auth B] SDF format, chain DA [auth A] SDF format, chain DB [auth B] SDF format, chain EB [auth B] SDF format, chain FB [auth B] SDF format, chain GB [auth B] SDF format, chain HB [auth B] SDF format, chain IB [auth B] SDF format, chain JB [auth B] SDF format, chain KB [auth B] SDF format, chain LB [auth B] SDF format, chain Q [auth A] SDF format, chain R [auth A] SDF format, chain S [auth A] SDF format, chain T [auth A] SDF format, chain U [auth A] SDF format, chain VA [auth B] SDF format, chain W [auth A] SDF format, chain WA [auth B] SDF format, chain X [auth A] SDF format, chain XA [auth B] SDF format, chain Y [auth A] SDF format, chain YA [auth B] SDF format, chain Z [auth A] SDF format, chain ZA [auth B] SDF format, chain CA [auth A] SDF format, chain V [auth A] MOL2 format, chain AA [auth A] MOL2 format, chain AB [auth B] MOL2 format, chain BA [auth A] MOL2 format, chain BB [auth B] MOL2 format, chain CB [auth B] MOL2 format, chain DA [auth A] MOL2 format, chain DB [auth B] MOL2 format, chain EB [auth B] MOL2 format, chain FB [auth B] MOL2 format, chain GB [auth B] MOL2 format, chain HB [auth B] MOL2 format, chain IB [auth B] MOL2 format, chain JB [auth B] MOL2 format, chain KB [auth B] MOL2 format, chain LB [auth B] MOL2 format, chain Q [auth A] MOL2 format, chain R [auth A] MOL2 format, chain S [auth A] MOL2 format, chain T [auth A] MOL2 format, chain U [auth A] MOL2 format, chain VA [auth B] MOL2 format, chain W [auth A] MOL2 format, chain WA [auth B] MOL2 format, chain X [auth A] MOL2 format, chain XA [auth B] MOL2 format, chain Y [auth A] MOL2 format, chain YA [auth B] MOL2 format, chain Z [auth A] MOL2 format, chain ZA [auth B] MOL2 format, chain CA [auth A] MOL2 format, chain V [auth A] mmCIF format, chain AA [auth A] mmCIF format, chain AB [auth B] mmCIF format, chain BA [auth A] mmCIF format, chain BB [auth B] mmCIF format, chain CB [auth B] mmCIF format, chain DA [auth A] mmCIF format, chain DB [auth B] mmCIF format, chain EB [auth B] mmCIF format, chain FB [auth B] mmCIF format, chain GB [auth B] mmCIF format, chain HB [auth B] mmCIF format, chain IB [auth B] mmCIF format, chain JB [auth B] mmCIF format, chain KB [auth B] mmCIF format, chain LB [auth B] mmCIF format, chain Q [auth A] mmCIF format, chain R [auth A] mmCIF format, chain S [auth A] mmCIF format, chain T [auth A] mmCIF format, chain U [auth A] mmCIF format, chain VA [auth B] mmCIF format, chain W [auth A] mmCIF format, chain WA [auth B] mmCIF format, chain X [auth A] mmCIF format, chain XA [auth B] mmCIF format, chain Y [auth A] mmCIF format, chain YA [auth B] mmCIF format, chain Z [auth A] mmCIF format, chain ZA [auth B] mmCIF format, chain CA [auth A] mmCIF format, chain V [auth A]	AA [auth A] AB [auth B] BA [auth A] BB [auth B] CA [auth A] AA [auth A], AB [auth B], BA [auth A], BB [auth B], CA [auth A], CB [auth B], DA [auth A], DB [auth B], EB [auth B], FB [auth B], GB [auth B], HB [auth B], IB [auth B], JB [auth B], KB [auth B], LB [auth B], Q [auth A], R [auth A], S [auth A], T [auth A], U [auth A], V [auth A], VA [auth B], W [auth A], WA [auth B], X [auth A], XA [auth B], Y [auth A], YA [auth B], Z [auth A], ZA [auth B]	CHLORIDE ION Cl VEXZGXHMUGYJMC-UHFFFAOYSA-M		Interactions Focus chain AA [auth A] Focus chain AB [auth B] Focus chain BA [auth A] Focus chain BB [auth B] Focus chain CA [auth A] Focus chain CB [auth B] Focus chain DA [auth A] Focus chain DB [auth B] Focus chain EB [auth B] Focus chain FB [auth B] Focus chain GB [auth B] Focus chain HB [auth B] Focus chain IB [auth B] Focus chain JB [auth B] Focus chain KB [auth B] Focus chain LB [auth B] Focus chain Q [auth A] Focus chain R [auth A] Focus chain S [auth A] Focus chain T [auth A] Focus chain U [auth A] Focus chain V [auth A] Focus chain VA [auth B] Focus chain W [auth A] Focus chain WA [auth B] Focus chain X [auth A] Focus chain XA [auth B] Focus chain Y [auth A] Focus chain YA [auth B] Focus chain Z [auth A] Focus chain ZA [auth B] Interactions & Density Focus chain AA [auth A] Focus chain AB [auth B] Focus chain BA [auth A] Focus chain BB [auth B] Focus chain CA [auth A] Focus chain CB [auth B] Focus chain DA [auth A] Focus chain DB [auth B] Focus chain EB [auth B] Focus chain FB [auth B] Focus chain GB [auth B] Focus chain HB [auth B] Focus chain IB [auth B] Focus chain JB [auth B] Focus chain KB [auth B] Focus chain LB [auth B] Focus chain Q [auth A] Focus chain R [auth A] Focus chain S [auth A] Focus chain T [auth A] Focus chain U [auth A] Focus chain V [auth A] Focus chain VA [auth B] Focus chain W [auth A] Focus chain WA [auth B] Focus chain X [auth A] Focus chain XA [auth B] Focus chain Y [auth A] Focus chain YA [auth B] Focus chain Z [auth A] Focus chain ZA [auth B]
MG Query on MG Download Ideal Coordinates CCD File SDF format, chain GA [auth A] SDF format, chain HA [auth A] SDF format, chain IA [auth A] SDF format, chain JA [auth A] SDF format, chain KA [auth A] SDF format, chain LA [auth A] SDF format, chain MA [auth A] SDF format, chain NA [auth A] 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 TB [auth B] SDF format, chain UB [auth B] MOL2 format, chain GA [auth A] MOL2 format, chain HA [auth A] MOL2 format, chain IA [auth A] MOL2 format, chain JA [auth A] MOL2 format, chain KA [auth A] MOL2 format, chain LA [auth A] MOL2 format, chain MA [auth A] MOL2 format, chain NA [auth A] 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 TB [auth B] MOL2 format, chain UB [auth B] mmCIF format, chain GA [auth A] mmCIF format, chain HA [auth A] mmCIF format, chain IA [auth A] mmCIF format, chain JA [auth A] mmCIF format, chain KA [auth A] mmCIF format, chain LA [auth A] mmCIF format, chain MA [auth A] mmCIF format, chain NA [auth A] 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 TB [auth B] mmCIF format, chain UB [auth B]	GA [auth A] HA [auth A] IA [auth A] JA [auth A] KA [auth A] GA [auth A], HA [auth A], IA [auth A], JA [auth A], KA [auth A], LA [auth A], MA [auth A], NA [auth A], PB [auth B], QB [auth B], RB [auth B], SB [auth B], TB [auth B], UB [auth B]	MAGNESIUM ION Mg JLVVSXFLKOJNIY-UHFFFAOYSA-N		Interactions Focus chain GA [auth A] Focus chain HA [auth A] Focus chain IA [auth A] Focus chain JA [auth A] Focus chain KA [auth A] Focus chain LA [auth A] Focus chain MA [auth A] Focus chain NA [auth A] Focus chain PB [auth B] Focus chain QB [auth B] Focus chain RB [auth B] Focus chain SB [auth B] Focus chain TB [auth B] Focus chain UB [auth B] Interactions & Density Focus chain GA [auth A] Focus chain HA [auth A] Focus chain IA [auth A] Focus chain JA [auth A] Focus chain KA [auth A] Focus chain LA [auth A] Focus chain MA [auth A] Focus chain NA [auth A] Focus chain PB [auth B] Focus chain QB [auth B] Focus chain RB [auth B] Focus chain SB [auth B] Focus chain TB [auth B] Focus chain UB [auth B]