4EY5

Crystal Structure of Recombinant Human Acetylcholinesterase in Complex with (-)-huperzine A

PDB DOI: https://doi.org/10.2210/pdb4EY5/pdb

Classification: HYDROLASE/HYDROLASE INHIBITOR
Organism(s): Homo sapiens
Expression System: Homo sapiens
Mutation(s): No

Deposited: 2012-05-01 Released: 2012-10-17
Deposition Author(s): Cheung, J., Rudolph, M., Burshteyn, F., Cassidy, M., Gary, E., Love, J., Height, J., Franklin, M.

Experimental Data Snapshot

Method: X-RAY DIFFRACTION
Resolution: 2.30 Å
R-Value Free: 0.212
R-Value Work: 0.176
R-Value Observed: 0.177

wwPDB Validation 3D Report Full Report

Ligand Structure Quality Assessment

This is version 2.1 of the entry. See complete history.

Literature

Structures of human acetylcholinesterase in complex with pharmacologically important ligands.

Cheung, J., Rudolph, M.J., Burshteyn, F., Cassidy, M.S., Gary, E.N., Love, J., Franklin, M.C., Height, J.J.

(2012) J Med Chem 55: 10282-10286

PubMed: 23035744 Search on PubMed
DOI: https://doi.org/10.1021/jm300871x
Primary Citation of Related Structures:
4EY4, 4EY5, 4EY6, 4EY7, 4EY8

PubMed Abstract:
Human acetylcholinesterase (AChE) is a significant target for therapeutic drugs. Here we present high resolution crystal structures of human AChE, alone and in complexes with drug ligands; donepezil, an Alzheimer's disease drug, binds differently to human AChE than it does to Torpedo AChE. These crystals of human AChE provide a more accurate platform for further drug development than previously available.

Organizational Affiliation

New York Structural Biology Center, New York, New York 10027, USA.

Macromolecule Content

Total Structure Weight: 121.21 kDa
Atom Count: 8,878
Modelled Residue Count: 1,065
Deposited Residue Count: 1,084
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	542	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
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, D	3		N-Glycosylation	Interactions Focus chain C Focus chain D Interactions & Density Focus chain C Focus chain D
Glycosylation Resources
GlyTouCan: G21290RB GlyCosmos: G21290RB GlyGen: G21290RB

Small Molecules

Ligands 5 Unique
ID	Chains	Name / Formula / InChI Key	2D Diagram	3D Interactions
HUP Query on HUP Download Ideal Coordinates CCD File SDF format, chain E [auth A] SDF format, chain J [auth B] MOL2 format, chain E [auth A] MOL2 format, chain J [auth B]	E [auth A], J [auth B]	Huperzine A C₁₅ H₁₈ N₂ O ZRJBHWIHUMBLCN-YQEJDHNASA-N		Interactions Focus chain E [auth A] Focus chain J [auth B] Interactions & Density Focus chain E [auth A] Focus chain J [auth B]
NAG Query on NAG Download Ideal Coordinates CCD File SDF format, chain I [auth B] MOL2 format, chain I [auth B]	I [auth B]	2-acetamido-2-deoxy-beta-D-glucopyranose C₈ H₁₅ N O₆ OVRNDRQMDRJTHS-FMDGEEDCSA-N		Interactions Focus chain I [auth B] Interactions & Density Focus chain I [auth B]
DMS Query on DMS Download Ideal Coordinates CCD File SDF format, chain F [auth A] SDF format, chain K [auth B] MOL2 format, chain F [auth A] MOL2 format, chain K [auth B]	F [auth A], K [auth B]	DIMETHYL SULFOXIDE C₂ H₆ O S IAZDPXIOMUYVGZ-UHFFFAOYSA-N		Interactions Focus chain F [auth A] Focus chain K [auth B] Interactions & Density Focus chain F [auth A] Focus chain K [auth B]
EDO Query on EDO Download Ideal Coordinates CCD File SDF format, chain G [auth A] SDF format, chain H [auth A] SDF format, chain L [auth B] MOL2 format, chain G [auth A] MOL2 format, chain H [auth A] MOL2 format, chain L [auth B]	G [auth A], H [auth A], L [auth B]	1,2-ETHANEDIOL C₂ H₆ O₂ LYCAIKOWRPUZTN-UHFFFAOYSA-N		Interactions Focus chain G [auth A] Focus chain H [auth A] Focus chain L [auth B] Interactions & Density Focus chain G [auth A] Focus chain H [auth A] Focus chain L [auth B]
NO3 Query on NO3 Download Ideal Coordinates CCD File SDF format, chain M [auth B] SDF format, chain N [auth B] MOL2 format, chain M [auth B] MOL2 format, chain N [auth B]	M [auth B], N [auth B]	NITRATE ION N O₃ NHNBFGGVMKEFGY-UHFFFAOYSA-N		Interactions Focus chain M [auth B] Focus chain N [auth B] Interactions & Density Focus chain M [auth B] Focus chain N [auth B]

Binding Affinity Annotations
ID	Source	Binding Affinity
HUP	BindingDB: 4EY5	IC50: min: 21, max: 4300 (nM) from 18 assay(s)

Experimental Data & Validation

Experimental Data

Method: X-RAY DIFFRACTION
Resolution: 2.30 Å
R-Value Free: 0.212
R-Value Work: 0.176
R-Value Observed: 0.177
Space Group: P 3₁ 2 1

Unit Cell:

Length ( Å )	Angle ( ˚ )
a = 105.222	α = 90
b = 105.222	β = 90
c = 323.289	γ = 120

Software Package:

Software Name	Purpose
DENZO	data reduction
SCALEPACK	data scaling
PHENIX	refinement
PDB_EXTRACT	data extraction
HKL-2000	data collection
HKL-2000	data reduction
HKL-2000	data scaling

Structure Validation

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Ligand Structure Quality Assessment

Entry History

Deposition Data

Released Date: 2012-10-17

Deposition Author(s):

Revision History (Full details and data files)

Version 1.0: 2012-10-17
Type: Initial release
Version 1.1: 2012-12-12
Changes: Database references
Version 1.2: 2013-10-23
Changes: Non-polymer description
Version 1.3: 2017-11-15
Changes: Refinement description
Version 2.0: 2020-07-29
Type: Remediation
Reason: Carbohydrate remediation
Changes: Atomic model, Data collection, Derived calculations, Structure summary
Version 2.1: 2023-09-13
Changes: Data collection, Database references, Refinement description, Structure summary