Structure of acetylcholinesterase (E.C. 3.1.1.7) complexed with (S,S)-(-)-bis(12)-hupyridone at 2.15A resolution

(S,S)-(-)-N,N'-DI-5'-[5',6',7',8'-TETRAHYDRO- 2'(1'H)-QUINOLYNYL]-1,12-DIAMINODODECANE DIHYDROCHLORIDE

N-acetyl-beta-D-glucosamine; 2-acetamido-2-deoxy-beta-D-glucose; 2-acetamido-2-deoxy-D-glucose; 2-acetamido-2-deoxy-glucose; N-ACETYL-D-GLUCOSAMINE

Acetylcholinesterase Complexed with Bivalent Ligands Related to Huperzine A: Experimental Evidence for Species-Dependent Protein-Ligand Complementarity

Dimerization of an Inactive Fragment of Huperzine a Produces a Drug with Twice the Potency of the Natural Product

Structure of Acetylcholinesterase Complexed with the Nootropic Alkaloid, (-)-Huperzine A

Prediction of the Binding Sites of Huperzine a in Acetylcholinesterase by Docking Studies

Atomic Structure of Acetylcholinesterase from Torpedo Californica: A Prototypic Acetylcholine-Binding Protein

NAG A 1537 HAS WRONG CHIRALITY AT ATOM C1

DDHSELLVNTKSGKVMGTRVPVLSSHISAFLGIPFAEPPVGNMRFRRPEPKKPWSGVWNASTYPNNCQQYVDEQFPGFSG
SEMWNPNREMSEDCLYLNIWVPSPRPKSTTVMVWIYGGGFYSGSSTLDVYNGKYLAYTEEVVLVSLSYRVGAFGFLALHG
SQEAPGNVGLLDQRMALQWVHDNIQFFGGDPKTVTIFGESAGGASVGMHILSPGSRDLFRRAILQSGSPNCPWASVSVAE
GRRRAVELGRNLNCNLNSDEELIHCLREKKPQELIDVEWNVLPFDSIFRFSFVPVIDGEFFPTSLESMLNSGNFKKTQIL
LGVNKDEGSFFLLYGAPGFSKDSESKISREDFMSGVKLSVPHANDLGLDAVTLQYTDWMDDNNGIKNRDGLDDIVGDHNV
ICPLMHFVNKYTKFGNGTYLYFFNHRASNLVWPEWMGVIHGYEIEFVFGLPLVKELNYTAEEEALSRRIMHYWATFAKTG
NPNEPHSQESKWPLFTTKEQKFIDLNTEPMKVHQRLRVQMCVFWNQFLPKLLNATACDGELSS

SYNTHETIC BIVALENT HUPA-LIKE DIMER, (S, S)-(-)-BIS(12)-HUPYRIDONE ((S, S)-(-)-N, N'-DI-5'- -[5', 6', 7', 8'-TETRAHYDRO-2'(1'H)-QUINOLINONYL] 1, 12-DIAMINODODECANE) DIHYDROCHLORIDE, WITH ONE MONOMER UNIT BOUND TO THE 'ANIONIC' SUBSITE, NEAR THE BOTTOM OF THE ACTIVE SITE GORGE, AND THE SECOND MONOMER UNIT BOUND TO THE 'PERIPHERAL' ANIONIC SITE AT THE TOP OF THE GORGE, THUS SPANNING THE ACTIVE SITE GORGE.

PROTEIN WAS CRYSTALLISED FROM 28-30% V/V PEG 200 0.5M MES PH 5.8 AT 4 DEG. CELSIUS; THEN SOAKED IN IN MOTHER LIQUOR (40% V/V PEG 200 IN 0.1 M MES BUFFER, PH 5.8) CONTAINING 10MM (S,S)-(-)-BIS(12)-HUPYRIDONE DIHYDROCHLORIDE FOR 2 DAYS

ACETYLCHOLINESTERASE COMPLEXED WITH TACRINE

ACETYLCHOLINESTERASE COMPLEXED WITH DECAMETHONIUM

TRANSITION STATE ANALOG: ACETYLCHOLINESTERASE COMPLEXED WITH M-(N,N,N-TRIMETHYLAMMONIO) TRIFLUOROACETOPHENONE

ACETYLCHOLINESTERASE COMPLEXED WITH EDROPHONIUM, LAUE DATA

METHYLPHOSPHONYLATED ACETYLCHOLINESTERASE (AGED) OBTAINED BY REACTION WITH O- ISOPROPYLMETHYLPHOSPHONOFLUORIDATE (GB, SARIN)

STRUCTURE OF ACETYLCHOLINESTERASE COMPLEXED WITH (-)-GALANTHAMINE AT 2.3A RESOLUTION

TORPEDO CALIFORNICA ACETYLCHOLINESTERASE COMPLEXED WITH BW284C51

STRUCTURE OF ACETYLCHOLINESTERASE COMPLEXED WITH (-)-HUPRINE X AT 2.1A RESOLUTION

NATIVE ACETYLCHOLINESTERASE (E.C. 3.1.1.7 ) FROM TORPEDO CALIFORNICA AT 1.8A RESOLUTION

THREE DIMENSIONAL STRUCTURE OF THE ANTI- ALZHEIMER DRUG, E2020 (ARICEPT), COMPLEXED WITH ITS TARGET ACETYLCHOLINESTERASE

ACETYLCHOLINESTERASE COMPLEXED WITH FASCICULIN- II

STRUCTURE OF ACETYLCHOLINESTERASE COMPLEXE WITH (+)-HUPERZINE A AT 2.1A RESOLUTION

STRUCTURE OF ACETYLCHOLINESTERASE COMPLEXED WITH HUPERZINE B AT 2.35A RESOLUTION

ACETYLCHOLINESTERASE (E.C. 3.1.1.7) COMPLEXED WITH RIVASTIGMINE

ACETYLCHOLINESTERASE (E.C. 3.1.1.7) COMPLEXED WITH NAP

X-RAY CRYSTAL STRUCTURE OF COMPLEX BETWEEN TORPEDO CALIFORNICA ACHE AND A REVERSIBLE INHIBITOR, 4-AMINO-5-FLUORO-2-METHYL-3-( 3-TRIFLUOROACETYLBENZYLTHIOMETHYL)QUINOLINE

STRUCTURE OF ACETYLCHOLINESTERASE (E.C. 3.1.1.7) COMPLEXED WITH (S,S)-(-)-BIS(10)-HUPYRIDONE AT 2.15A RESOLUTION

A NEUTRAL MOLECULE IN CATION-BINDING SITE: SPECIFIC BINDINGOF PEG-SH TO ACETYLCHOLINESTERASE FROM TORPEDO CALIFORNICA

ACETYLCHOLINESTERASE COMPLEXED WITH MF268

SPECIFIC CHEMICAL AND STRUCTURAL DAMAGE AT NINE TIME POINTS (POINT A) CAUSED BY INTENSE SYNCHROTRON RADIATION TO TORPEDO CALIFORNICA ACETYLCHOLINESTERASE

SPECIFIC CHEMICAL AND STRUCTURAL DAMAGE AT NINE TIME POINTS (POINT B) CAUSED BY INTENSE SYNCHROTRON RADIATION TO TORPEDO CALIFORNICA ACETYLCHOLINESTERASE

SPECIFIC CHEMICAL AND STRUCTURAL DAMAGE AT NINE TIME POINTS (POINT C) CAUSED BY INTENSE SYNCHROTRON RADIATION TO TORPEDO CALIFORNICA ACETYLCHOLINESTERASE

SPECIFIC CHEMICAL AND STRUCTURAL DAMAGE AT NINE TIME POINTS (POINT D) CAUSED BY INTENSE SYNCHROTRON RADIATION TO TORPEDO CALIFORNICA ACETYLCHOLINESTERASE

SPECIFIC CHEMICAL AND STRUCTURAL DAMAGE AT NINE TIME POINTS (POINT E) CAUSED BY INTENSE SYNCHROTRON RADIATION TO TORPEDO CALIFORNICA ACETYLCHOLINESTERASE

SPECIFIC CHEMICAL AND STRUCTURAL DAMAGE AT NINE TIME POINTS (POINT F) CAUSED BY INTENSE SYNCHROTRON RADIATION TO TORPEDO CALIFORNICA ACETYLCHOLINESTERASE

SPECIFIC CHEMICAL AND STRUCTURAL DAMAGE AT NINE TIME POINTS (POINT G) CAUSED BY INTENSE SYNCHROTRON RADIATION TO TORPEDO CALIFORNICA ACETYLCHOLINESTERASE

SPECIFIC CHEMICAL AND STRUCTURAL DAMAGE AT NINE TIME POINTS (POINT H) CAUSED BY INTENSE SYNCHROTRON RADIATION TO TORPEDO CALIFORNICA ACETYLCHOLINESTERASE

SPECIFIC CHEMICAL AND STRUCTURAL DAMAGE AT NINE TIME POINTS (POINT I) CAUSED BY INTENSE SYNCHROTRON RADIATION TO TORPEDO CALIFORNICA ACETYLCHOLINESTERASE

TORPEDO CALIFORNICA ACETYLCHOLINESTERASE INHIBITED BY NERVE AGENT GD (SOMAN).

ACETYLCHOLINESTERASE COMPLEXED WITH HUPERZINE A

METHYLPHOSPHONYLATED ACETYLCHOLINESTERASE (AGED) OBTAINED BY REACTION WITH O-ETHYL-S-[2-[ BIS(1-METHYLETHYL) AMINO]ETHYL] METHYLPHOSPHONOTHIOATE (VX)

O-ETHYLMETHYLPHOSPHONYLATED ACETYLCHOLINESTERASE OBTAINED BY REACTION WITH O-ETHYL-S-[2-[ BIS(1-METHYLETHYL) AMINO]ETHYL] METHYLPHOSPHONOTHIOATE (VX)

NATIVE ACETYLCHOLINESTERASE FROM TORPEDO CALIFORNICA

ACETYLCHOLINESTERASE COMPLEXED WITH EDROPHONIUM, MONOCHROMATIC DATA

X-RAY STRUCTURE OF AGED DI-ISOPROPYL- PHOSPHORO-FLUORIDATE (DFP) BOUND TO ACETYLCHOLINESTERASE

THEORETICAL MODEL OF (R)-E2020 BOUND ACETYLCHOLINESTERASE COMPLEX, 3 STRUCTURES

THEORETICAL MODEL OF (S)-E2020 BOUND ACETYLCHOLINESTERASE COMPLEX, 3 STRUCTURE

COMPOUND HYDROLYZES CHOLINE RELEASED INTO THE SYNAPSE.
CATALYTIC ACTIVITY: ACETYLCHOLINE + H(2)O = CHOLINE +
ACETATE. INHIBITORS OF THE ENZYME ACETYLCHOLINESTERASE
(ACHE) IMPROVE THE COGNITIVE ABILITIES OF INDIVIDUALS WITH
EARLY STAGE ALZHEIMER'S DISEASE. (-)-HUPERZINE A
((-)-HUPA), A NATURAL PRODUCT USED IN TRADITIONAL CHINESE
HERBAL MEDICINE, IS AMONG THE POTENT ACHE INHIBITORS USED
IN THIS TREATMENT. THE LIGAND, (S,S)-(-)-BIS(12)-HUPYRIDONE
((S,S)-(-)-N,N'-DI-5'-[5',6',7',8'-TETRAHYDRO-2'(1'H)-
QUINOLINONYL]-1,12-DIAMINODODECANE) DIHYDROCHLORIDE, AN
ALKYLENE LINKED DIMER OF FRAGMENTS OF THE HUPA STRUCTURE,
HUPYRIDONE (5-AMINO-5,6,7,8-TETRAHYDROQUINOLINONE), HAVE
BEEN SHOWN TO EXHIBIT POTENT INHIBITION OF ACHE. ONE
HUPYRIDONE UNIT BINDS TO THE 'ANIONIC' SUBSITE OF THE
ACTIVE SITE, NEAR THE BOTTOM OF THE ACTIVE SITE GORGE OF
TCACHE, ADJACENT TO TRP84, AS SEEN FOR THE TCACHE/(-)-HUPA
COMPLEX, AND THE SECOND HUPYRIDONE UNIT NEAR TO TRP279 IN
THE 'PERIPHERAL' ANIONIC SITE AT THE TOP OF THE GORGE, THUS
SPANNING THE ACTIVE SITE GORGE.

SEVERAL RESIDUES ARE NOT SEEN IN THE CRYSTAL STRUCTURE, DUE TO DISORDER. THESE INCLUDE ASP 1, ASP 2, HIS 3 AND THE C-TERMINAL RESIDUES AFTER THR 535. SEVERAL RESIDUES MISSING IN CHAIN BREAK, FROM HIS 486 - GLU 489 (INCLUSIVE).

SERINE HYDROLASE, ACETYLCHOLINESTERASE, NEUROTRANSMITTER CLEAVAGE, ALZHEIMER'S DISEASE, BIVALENT LIGAND, DUAL-SITE BINDING, INHIBITOR, HUPERZINE A, HYDROLASE, SERINE ESTERASE SYNAPSE, MEMBRANE, NERVE, MUSCLE, GPI-ANCHOR NEUROTRANSMITTER DEGRADATION, GLYCOPROTEIN, BIS(12)-HUPYRID