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HEADER CHOLINESTERASE 08-AUG-00 1E66
TITLE STRUCTURE OF ACETYLCHOLINESTERASE COMPLEXED WITH
TITLE 2 (-)-HUPRINE X AT 2.1A RESOLUTION
COMPND MOL_ID: 1;
COMPND 2 MOLECULE: ACETYLCHOLINESTERASE;
COMPND 3 CHAIN: A;
COMPND 4 EC: 3.1.1.7;
COMPND 5 OTHER_DETAILS: SYNTHETIC HYBRID, HUPRINE X, BOUND AT THE
COMPND 6 BOTTOM OF THE ACTIVE SITE GORGE
SOURCE MOL_ID: 1;
SOURCE 2 ORGANISM_SCIENTIFIC: TORPEDO CALIFORNICA;
SOURCE 3 ORGANISM_COMMON: PACIFIC ELECTRIC RAY;
SOURCE 4 VARIANT: G2 FORM;
SOURCE 5 ORGAN: ELECTRIC ORGAN;
SOURCE 6 TISSUE: ELECTROPLAQUE
KEYWDS CHOLINESTERASE, HUPRINE X, ALZHEIMER'S DISEASE, CHEMICAL
KEYWDS 2 HYBRID
EXPDTA X-RAY DIFFRACTION
AUTHOR H.DVIR,M.HAREL,I.SILMAN,J.L.SUSSMAN
REVDAT 1 02-AUG-01 1E66 0
JRNL AUTH H.DVIR,M.HAREL,I.SILMAN,J.L.SUSSMAN
JRNL TITL STRUCTURE OF ACETYLCHOLINESTERASE COMPLEXED WITH
JRNL TITL 2 (-)-HUPRINE X AT 2.1A RESOLUTION
JRNL REF TO BE PUBLISHED
JRNL REFN
REMARK 2
REMARK 2 RESOLUTION. 2.1 ANGSTROMS.
REMARK 3
REMARK 3 REFINEMENT.
REMARK 3 PROGRAM : CNS 1.0
REMARK 3 AUTHORS : BRUNGER,ADAMS,CLORE,DELANO,GROS,
REMARK 3 GROSSE-KUNSTLEVE,JIANG,KUSZEWSKI,NILGES,
REMARK 3 PANNU,READ,RICE,SIMONSON,WARREN
REMARK 3
REMARK 3 REFINEMENT TARGET : NULL
REMARK 3
REMARK 3 DATA USED IN REFINEMENT.
REMARK 3 RESOLUTION RANGE HIGH (ANGSTROMS) : 2.10
REMARK 3 RESOLUTION RANGE LOW (ANGSTROMS) : 29.42
REMARK 3 DATA CUTOFF (SIGMA(F)) : 0.0
REMARK 3 OUTLIER CUTOFF HIGH (RMS(ABS(F))) : 2910778.11
REMARK 3 COMPLETENESS (WORKING+TEST) (%) : 76.0
REMARK 3 NUMBER OF REFLECTIONS : 45083
REMARK 3
REMARK 3 FIT TO DATA USED IN REFINEMENT.
REMARK 3 CROSS-VALIDATION METHOD : THROUGHOUT
REMARK 3 FREE R VALUE TEST SET SELECTION : RANDOM
REMARK 3 R VALUE (WORKING SET) : 0.177
REMARK 3 FREE R VALUE : 0.205
REMARK 3 FREE R VALUE TEST SET SIZE (%) : 10.1
REMARK 3 FREE R VALUE TEST SET COUNT : 4542
REMARK 3 ESTIMATED ERROR OF FREE R VALUE : 0.003
REMARK 3
REMARK 3 FIT IN THE HIGHEST RESOLUTION BIN.
REMARK 3 TOTAL NUMBER OF BINS USED : 6
REMARK 3 BIN RESOLUTION RANGE HIGH (A) : 2.10
REMARK 3 BIN RESOLUTION RANGE LOW (A) : 2.23
REMARK 3 BIN COMPLETENESS (WORKING+TEST) (%) : 22.5
REMARK 3 REFLECTIONS IN BIN (WORKING SET) : 1967
REMARK 3 BIN R VALUE (WORKING SET) : 0.235
REMARK 3 BIN FREE R VALUE : 0.246
REMARK 3 BIN FREE R VALUE TEST SET SIZE (%) : 10.5
REMARK 3 BIN FREE R VALUE TEST SET COUNT : 231
REMARK 3 ESTIMATED ERROR OF BIN FREE R VALUE : 0.016
REMARK 3
REMARK 3 NUMBER OF NON-HYDROGEN ATOMS USED IN REFINEMENT.
REMARK 3 PROTEIN ATOMS : 4272
REMARK 3 NUCLEIC ACID ATOMS : 0
REMARK 3 HETEROGEN ATOMS : 49
REMARK 3 SOLVENT ATOMS : 500
REMARK 3
REMARK 3 B VALUES.
REMARK 3 FROM WILSON PLOT (A**2) : 9.2
REMARK 3 MEAN B VALUE (OVERALL, A**2) : 34.4
REMARK 3 OVERALL ANISOTROPIC B VALUE.
REMARK 3 B11 (A**2) : 6.58
REMARK 3 B22 (A**2) : 6.58
REMARK 3 B33 (A**2) : -13.17
REMARK 3 B12 (A**2) : 4.65
REMARK 3 B13 (A**2) : 0.00
REMARK 3 B23 (A**2) : 0.00
REMARK 3
REMARK 3 ESTIMATED COORDINATE ERROR.
REMARK 3 ESD FROM LUZZATI PLOT (A) : 0.22
REMARK 3 ESD FROM SIGMAA (A) : 0.21
REMARK 3 LOW RESOLUTION CUTOFF (A) : 5.00
REMARK 3
REMARK 3 CROSS-VALIDATED ESTIMATED COORDINATE ERROR.
REMARK 3 ESD FROM C-V LUZZATI PLOT (A) : 0.26
REMARK 3 ESD FROM C-V SIGMAA (A) : 0.24
REMARK 3
REMARK 3 RMS DEVIATIONS FROM IDEAL VALUES.
REMARK 3 BOND LENGTHS (A) : 0.012
REMARK 3 BOND ANGLES (DEGREES) : 1.6
REMARK 3 DIHEDRAL ANGLES (DEGREES) : 23.3
REMARK 3 IMPROPER ANGLES (DEGREES) : 1.05
REMARK 3
REMARK 3 ISOTROPIC THERMAL MODEL : RESTRAINED
REMARK 3
REMARK 3 ISOTROPIC THERMAL FACTOR RESTRAINTS. RMS SIGMA
REMARK 3 MAIN-CHAIN BOND (A**2) : 1.19 ; 1.50
REMARK 3 MAIN-CHAIN ANGLE (A**2) : 1.84 ; 2.00
REMARK 3 SIDE-CHAIN BOND (A**2) : 5.40 ; 2.00
REMARK 3 SIDE-CHAIN ANGLE (A**2) : 6.87 ; 2.50
REMARK 3
REMARK 3 BULK SOLVENT MODELING.
REMARK 3 METHOD USED : FLAT MODEL
REMARK 3 KSOL : 0.345552
REMARK 3 BSOL : 70.6596
REMARK 3
REMARK 3 NCS MODEL : NONE
REMARK 3
REMARK 3 NCS RESTRAINTS. RMS SIGMA/WEIGHT
REMARK 3 GROUP 1 POSITIONAL (A) : NULL ; NULL
REMARK 3 GROUP 1 B-FACTOR (A**2) : NULL ; NULL
REMARK 3
REMARK 3 PARAMETER FILE 1 : PROTEIN_REP.PARAM
REMARK 3 PARAMETER FILE 2 : WATER_REP.PARAM
REMARK 3 PARAMETER FILE 3 : CARBOHYDRATE.PARAM
REMARK 3 PARAMETER FILE 4 : HUP.PAR
REMARK 3 TOPOLOGY FILE 1 : PROTEIN.TOP
REMARK 3 TOPOLOGY FILE 2 : WATER.TOP
REMARK 3 TOPOLOGY FILE 3 : CARBOHYDRATE.TOP
REMARK 3 TOPOLOGY FILE 4 : HUP.TOP
REMARK 3
REMARK 3 OTHER REFINEMENT REMARKS: PROLINE 485 IS OUT OF THE 3FO-2FC
REMARK 3 DENSITY MAP.
REMARK 3 THE CONSERVED WATER MOLECULE THAT BELONGS TO THE OXYANION
REMARK 3 HOLE (HOH 682 IN 2ACE NUMBERING) IS ABSENT IN THIS ENTRY
REMARK 3 ALTHOUGH A POSITIVE DIFFERENCE DENSITY HAD BEEN DETECTED IN
REMARK 3 THAT LOCATION. HERE THIS WATER WAS NOT MODELED BECAUSE OF
REMARK 3 INSUFICIENT SPACE FOR IT DUE TO MOVEMENT OF SER 200.
REMARK 4
REMARK 4 1E66 COMPLIES WITH FORMAT V. 2.3, 09-JULY-1998
REMARK 100
REMARK 100 THIS ENTRY HAS BEEN PROCESSED BY EBI ON 9-AUG-2000.
REMARK 100 THE EBI ID CODE IS EBI-5222.
REMARK 200
REMARK 200 EXPERIMENTAL DETAILS
REMARK 200 EXPERIMENT TYPE : X-RAY DIFFRACTION
REMARK 200 DATE OF DATA COLLECTION : 15-AUG-1999
REMARK 200 TEMPERATURE (KELVIN) : 120
REMARK 200 PH : 5.6
REMARK 200 NUMBER OF CRYSTALS USED : 1
REMARK 200
REMARK 200 SYNCHROTRON (Y/N) : Y
REMARK 200 RADIATION SOURCE : NSLS BEAMLINE X12C
REMARK 200 BEAMLINE : X12C
REMARK 200 X-RAY GENERATOR MODEL : NULL
REMARK 200 MONOCHROMATIC OR LAUE (M/L) : M
REMARK 200 WAVELENGTH OR RANGE (A) : 0.98
REMARK 200 MONOCHROMATOR : NULL
REMARK 200 OPTICS : MIRRORS
REMARK 200
REMARK 200 DETECTOR TYPE : IMAGE PLATE
REMARK 200 DETECTOR MANUFACTURER : MAR-RESEARCH
REMARK 200 INTENSITY-INTEGRATION SOFTWARE : DENZO
REMARK 200 DATA SCALING SOFTWARE : SCALEPACK
REMARK 200
REMARK 200 NUMBER OF UNIQUE REFLECTIONS : 60094
REMARK 200 RESOLUTION RANGE HIGH (A) : 2.1
REMARK 200 RESOLUTION RANGE LOW (A) : 29.42
REMARK 200 REJECTION CRITERIA (SIGMA(I)) : NONE
REMARK 200
REMARK 200 OVERALL.
REMARK 200 COMPLETENESS FOR RANGE (%) : 76.0
REMARK 200 DATA REDUNDANCY : 11.6
REMARK 200 R MERGE (I) : NULL
REMARK 200 R SYM (I) : 0.061
REMARK 200 FOR THE DATA SET : 16.0
REMARK 200
REMARK 200 IN THE HIGHEST RESOLUTION SHELL.
REMARK 200 HIGHEST RESOLUTION SHELL, RANGE HIGH (A) : 2.1
REMARK 200 HIGHEST RESOLUTION SHELL, RANGE LOW (A) : 2.18
REMARK 200 COMPLETENESS FOR SHELL (%) : 17.6
REMARK 200 DATA REDUNDANCY IN SHELL : 3.52
REMARK 200 R MERGE FOR SHELL (I) : NULL
REMARK 200 R SYM FOR SHELL (I) : 0.270
REMARK 200 FOR SHELL : 2.24
REMARK 200
REMARK 200 DIFFRACTION PROTOCOL: SINGLE WAVELENGTH
REMARK 200 METHOD USED TO DETERMINE THE STRUCTURE: MOLECULAR REPLACEMENT
REMARK 200 SOFTWARE USED: RIGID BODY (CNS)
REMARK 200 STARTING MODEL: PDB ENTRY 2ACE
REMARK 200
REMARK 200 REMARK: NULL
REMARK 280
REMARK 280 CRYSTAL
REMARK 280 SOLVENT CONTENT, VS (%): 68.0
REMARK 280 MATTHEWS COEFFICIENT, VM (ANGSTROMS**3/DA): 3.80
REMARK 280
REMARK 280 CRYSTALLIZATION CONDITIONS: PROTEIN WAS CRYSTALLISED
REMARK 280 FROM 35-40% W/V PEG 200 0.3M MES PH 5.6 4 DEG. CELSIUS
REMARK 290
REMARK 290 CRYSTALLOGRAPHIC SYMMETRY
REMARK 290 SYMMETRY OPERATORS FOR SPACE GROUP: P 31 2 1
REMARK 290
REMARK 290 SYMOP SYMMETRY
REMARK 290 NNNMMM OPERATOR
REMARK 290 1555 X,Y,Z
REMARK 290 2555 -Y,X-Y,Z+1/3
REMARK 290 3555 Y-X,-X,Z+2/3
REMARK 290 4555 Y,X,-Z
REMARK 290 5555 X-Y,-Y,2/3-Z
REMARK 290 6555 -X,Y-X,1/3-Z
REMARK 290
REMARK 290 WHERE NNN -> OPERATOR NUMBER
REMARK 290 MMM -> TRANSLATION VECTOR
REMARK 290
REMARK 290 CRYSTALLOGRAPHIC SYMMETRY TRANSFORMATIONS
REMARK 290 THE FOLLOWING TRANSFORMATIONS OPERATE ON THE ATOM/HETATM
REMARK 290 RECORDS IN THIS ENTRY TO PRODUCE CRYSTALLOGRAPHICALLY
REMARK 290 RELATED MOLECULES.
REMARK 290 SMTRY1 1 1.000000 0.000000 0.000000 0.00000
REMARK 290 SMTRY2 1 0.000000 1.000000 0.000000 0.00000
REMARK 290 SMTRY3 1 0.000000 0.000000 1.000000 0.00000
REMARK 290 SMTRY1 2 -0.500000 -0.866025 0.000000 0.00000
REMARK 290 SMTRY2 2 0.866025 -0.500000 0.000000 0.00000
REMARK 290 SMTRY3 2 0.000000 0.000000 1.000000 46.05500
REMARK 290 SMTRY1 3 -0.500000 0.866025 0.000000 0.00000
REMARK 290 SMTRY2 3 -0.866025 -0.500000 0.000000 0.00000
REMARK 290 SMTRY3 3 0.000000 0.000000 1.000000 92.11000
REMARK 290 SMTRY1 4 -0.500000 0.866025 0.000000 0.00000
REMARK 290 SMTRY2 4 0.866025 0.500000 0.000000 0.00000
REMARK 290 SMTRY3 4 0.000000 0.000000 -1.000000 0.00000
REMARK 290 SMTRY1 5 1.000000 0.000000 0.000000 0.00000
REMARK 290 SMTRY2 5 0.000000 -1.000000 0.000000 0.00000
REMARK 290 SMTRY3 5 0.000000 0.000000 -1.000000 92.11000
REMARK 290 SMTRY1 6 -0.500000 -0.866025 0.000000 0.00000
REMARK 290 SMTRY2 6 -0.866025 0.500000 0.000000 0.00000
REMARK 290 SMTRY3 6 0.000000 0.000000 -1.000000 46.05500
REMARK 290
REMARK 290 REMARK: NULL
REMARK 300
REMARK 300 BIOMOLECULE: 1
REMARK 300 THIS ENTRY CONTAINS THE CRYSTALLOGRAPHIC ASYMMETRIC UNIT
REMARK 300 WHICH CONSISTS OF 1 CHAIN(S). SEE REMARK 350 FOR
REMARK 300 INFORMATION ON GENERATING THE BIOLOGICAL MOLECULE(S).
REMARK 300
REMARK 300 BIOLOGICAL UNIT: HOMODIMER
REMARK 350
REMARK 350 GENERATING THE BIOMOLECULE
REMARK 350 COORDINATES FOR A COMPLETE MULTIMER REPRESENTING THE KNOWN
REMARK 350 BIOLOGICALLY SIGNIFICANT OLIGOMERIZATION STATE OF THE
REMARK 350 MOLECULE CAN BE GENERATED BY APPLYING BIOMT TRANSFORMATIONS
REMARK 350 GIVEN BELOW. BOTH NON-CRYSTALLOGRAPHIC AND
REMARK 350 CRYSTALLOGRAPHIC OPERATIONS ARE GIVEN.
REMARK 350
REMARK 350 BIOMOLECULE: 1
REMARK 350 APPLY THE FOLLOWING TO CHAINS: A
REMARK 350 BIOMT1 1 1.000000 0.000000 0.000000 0.00000
REMARK 350 BIOMT2 1 0.000000 1.000000 0.000000 0.00000
REMARK 350 BIOMT3 1 0.000000 0.000000 1.000000 0.00000
REMARK 350 BIOMT1 2 -0.500000 0.866025 0.000000 0.00000
REMARK 350 BIOMT2 2 0.866025 0.500000 0.000000 0.00000
REMARK 350 BIOMT3 2 0.000000 0.000000 -1.000000 138.16500
REMARK 400
REMARK 400 COMPOUND
REMARK 400 HYDROLYZES CHOLINE RELEASED INTO THE SYNAPSE.
REMARK 400 CATALYTIC ACTIVITY: ACETYLCHOLINE + H(2)O = CHOLINE + ACETATE.
REMARK 400 INHIBITORS OF THE ENZYME ACETYLCHOLINESTERASE (ACHE) SLOW AND
REMARK 400 SOMETIMES REVERSE THE COGNITIVE DECLINE EXPERIENCED BY INDIVIDUALS
REMARK 400 WITH ALZHEIMER'S DISEASE. HUPERZINE A, A NATURAL PRODUCT USED IN
REMARK 400 TRADITIONAL CHINESE HERBAL MEDICINE, AND TACRINE (COGNEX) ARE AMONG
REMARK 400 THE POTENT ACHE INHIBITORS USED IN THIS TREATMENT.
REMARK 400 (-)-12-AMINO-3-CHLORO-9-ETHYL-6,7,10,11-TETRAHYDRO-7,11-
REMARK 400 METHANOCYCLOOCTA[B]QUINOLINE HYDROCHLORIDE (HUPRINE X), A HYBRID
REMARK 400 THAT COMBINES THE CARBOBICYCLIC SUBSTRUCTURE OF HUPERZINE A
REMARK 400 WITH WITH THE 4-AMINOQUINOLINE SUBSTRUCTURE OF TACRINE HUPRINE X
REMARK 400 BINDS TO HUMAN ACHE WITH AN INHIBITION CONSTANT K(I) OF 26 PM.
REMARK 400 HUPRINE X SHOWS NO DETECTABLE AFFINITY FOR THE EDROPHONIUM-ACHE
REMARK 400 COMPLEX. HUPRINE X BINDS TO THE ENZYME ACYLATION SITE IN THE
REMARK 400 ACTIVE SITE GORGE INTERFERES SLIGHTLY WITH THE BINDING OF
REMARK 400 PERIPHERAL SITE LIGANDS.
REMARK 465
REMARK 465 MISSING RESIDUES
REMARK 465 THE FOLLOWING RESIDUES WERE NOT LOCATED IN THE
REMARK 465 EXPERIMENT. (M=MODEL NUMBER; RES=RESIDUE NAME; C=CHAIN
REMARK 465 IDENTIFIER; SSSEQ=SEQUENCE NUMBER; I=INSERTION CODE.)
REMARK 465
REMARK 465 M RES C SSSEQI
REMARK 465 ASP A 1
REMARK 465 ASP A 2
REMARK 465 HIS A 3
REMARK 465 ALA A 536
REMARK 465 CYS A 537
REMARK 465 ASP A 538
REMARK 465 GLY A 539
REMARK 465 GLU A 540
REMARK 465 LEU A 541
REMARK 465 SER A 542
REMARK 465 SER A 543
REMARK 470
REMARK 470 MISSING ATOM
REMARK 470 THE FOLLOWING RESIDUES HAVE MISSING ATOMS (M=MODEL NUMBER;
REMARK 470 RES=RESIDUE NAME; C=CHAIN IDENTIFIER; SSEQ=SEQUENCE NUMBER;
REMARK 470 I=INSERTION CODE):
REMARK 470 M RES CSSEQI ATOMS
REMARK 470 LEU A 7 CG CD1 CD2
REMARK 470 ASN A 42 CG OD1 ND2
REMARK 470 ARG A 46 CD NE CZ NH1 NH2
REMARK 470 ARG A 47 CD NE CZ NH1 NH2
REMARK 470 LYS A 52 CD CE NZ
REMARK 470 GLU A 89 CD OE1 OE2
REMARK 470 GLN A 162 CD OE1 NE2
REMARK 470 LYS A 192 CD CE NZ
REMARK 470 ASN A 253 CG OD1 ND2
REMARK 470 ASN A 257 CG OD1 ND2
REMARK 470 GLU A 260 CD OE1 OE2
REMARK 470 GLU A 268 CG CD OE1 OE2
REMARK 470 LYS A 270 CE NZ
REMARK 470 GLU A 299 CD OE1 OE2
REMARK 470 GLU A 350 CD OE1 OE2
REMARK 470 ASP A 365 OD1 OD2
REMARK 470 ASN A 382 OD1 ND2
REMARK 470 LYS A 413 CD CE NZ
REMARK 470 GLU A 434 CD OE1 OE2
REMARK 470 LYS A 454 CD CE NZ
REMARK 470 GLU A 455 CG CD OE1 OE2
REMARK 470 LYS A 478 CG CD CE NZ
REMARK 470 HIS A 486 CG ND1 CD2 CE1 NE2
REMARK 470 GLN A 488 CD OE1 NE2
REMARK 470 GLU A 489 CD OE1 OE2
REMARK 470 SER A 490 OG
REMARK 470 LYS A 511 CD CE NZ
REMARK 470 GLN A 526 CD OE1 NE2
REMARK 500
REMARK 500 GEOMETRY AND STEREOCHEMISTRY
REMARK 500 SUBTOPIC: COVALENT BOND ANGLES
REMARK 500
REMARK 500 THE STEREOCHEMICAL PARAMETERS OF THE FOLLOWING RESIDUES
REMARK 500 HAVE VALUES WHICH DEVIATE FROM EXPECTED VALUES BY MORE
REMARK 500 THAN 6*RMSD (M=MODEL NUMBER; RES=RESIDUE NAME; C=CHAIN
REMARK 500 IDENTIFIER; SSEQ=SEQUENCE NUMBER; I=INSERTION CODE).
REMARK 500
REMARK 500 STANDARD TABLE:
REMARK 500 FORMAT: (10X,I3,1X,A3,1X,A1,I4,A1,3(1X,A4,2X),12X,F5.1)
REMARK 500
REMARK 500 EXPECTED VALUES: ENGH AND HUBER, 1991
REMARK 500
REMARK 500 M RES CSSEQI ATM1 ATM2 ATM3
REMARK 500 PHE A 155 N - CA - C ANGL. DEV. = 10.0 DEGREES
REMARK 500 ASN A 183 N - CA - C ANGL. DEV. = 10.3 DEGREES
REMARK 500 ARG A 216 N - CA - C ANGL. DEV. = 9.5 DEGREES
REMARK 500 ASP A 285 N - CA - C ANGL. DEV. = -12.9 DEGREES
REMARK 500 GLY A 328 N - CA - C ANGL. DEV. = 10.1 DEGREES
REMARK 500 GLY A 335 N - CA - C ANGL. DEV. = 9.7 DEGREES
REMARK 500 ILE A 439 N - CA - C ANGL. DEV. = 11.0 DEGREES
REMARK 500 ASN A 457 N - CA - C ANGL. DEV. = 10.2 DEGREES
REMARK 500 THR A 479 N - CA - C ANGL. DEV. = 9.7 DEGREES
REMARK 500 LEU A 494 CA - CB - CG ANGL. DEV. = 11.0 DEGREES
REMARK 500
REMARK 500 REMARK: NULL
REMARK 500
REMARK 500 GEOMETRY AND STEREOCHEMISTRY
REMARK 500 SUBTOPIC: CLOSE CONTACTS IN SAME ASYMMETRIC UNIT
REMARK 500
REMARK 500 THE FOLLOWING ATOMS ARE IN CLOSE CONTACT.
REMARK 500
REMARK 500 ATM1 RES C SSEQI ATM2 RES C SSEQI DISTANCE
REMARK 500
REMARK 500 O HOH Z 22 O HOH Z 169 1.96
REMARK 500 O HOH Z 22 O HOH Z 24 2.06
REMARK 500 O HOH Z 24 O HOH Z 169 2.02
REMARK 525
REMARK 525 SOLVENT
REMARK 525
REMARK 525 THE SOLVENT MOLECULES ARE GIVEN CHAIN IDENTIFIERS TO
REMARK 525 INDICATE THE PROTEIN CHAIN TO WHICH THEY ARE MOST CLOSELY
REMARK 525 ASSOCIATED WITH:
REMARK 525 PROTEIN CHAIN SOLVENT CHAIN
REMARK 525 A Z
REMARK 800
REMARK 800 SITE
REMARK 800 SITE_IDENTIFIER: HUX
REMARK 800 SITE_DESCRIPTION: (-)-HUPRINE X BINDING SITE
REMARK 900
REMARK 900 RELATED ENTRIES
REMARK 900 RELATED ID: 3ACE RELATED DB: PDB
REMARK 900 THEORETICAL MODEL OF (R)-E2020 BOUND
REMARK 900 ACETYLCHOLINESTERASE COMPLEX, 3 STRUCTURES
REMARK 900 RELATED ID: 2DFP RELATED DB: PDB
REMARK 900 X-RAY STRUCTURE OF AGED
REMARK 900 DI-ISOPROPYL-PHOSPHORO-FLUORIDATE (DFP) BOUND TO
REMARK 900 ACETYLCHOLINESTERASE
REMARK 900 RELATED ID: 2ACE RELATED DB: PDB
REMARK 900 NATIVE ACETYLCHOLINESTERASE FROM TORPEDO CALIFORNICA
REMARK 900 RELATED ID: 2ACK RELATED DB: PDB
REMARK 900 ACETYLCHOLINESTERASE COMPLEXED WITH EDROPHONIUM,
REMARK 900 MONOCHROMATIC DATA
REMARK 900 RELATED ID: 1VXO RELATED DB: PDB
REMARK 900 METHYLPHOSPHONYLATED ACETYLCHOLINESTERASE (AGED)
REMARK 900 OBTAINED BY REACTION WITH
REMARK 900 O-ETHYL-S-[2-[BIS(1-METHYLETHYL) AMINO]ETHYL]
REMARK 900 METHYLPHOSPHONOTHIOATE (VX)
REMARK 900 RELATED ID: 1VXR RELATED DB: PDB
REMARK 900 O-ETHYLMETHYLPHOSPHONYLATED ACETYLCHOLINESTERASE
REMARK 900 OBTAINED BY REACTION WITH
REMARK 900 O-ETHYL-S-[2-[BIS(1-METHYLETHYL) AMINO]ETHYL]
REMARK 900 METHYLPHOSPHONOTHIOATE (VX)
REMARK 900 RELATED ID: 1VOT RELATED DB: PDB
REMARK 900 ACETYLCHOLINESTERASE COMPLEXED WITH HUPERZINE A
REMARK 900 RELATED ID: 1SOM RELATED DB: PDB
REMARK 900 TORPEDO CALIFORNICA ACETYLCHOLINESTERASE INHIBITED BY
REMARK 900 NERVE AGENT GD (SOMAN).
REMARK 900 RELATED ID: 1QTI RELATED DB: PDB
REMARK 900 ACETYLCHOLINESTERASE
REMARK 900 RELATED ID: 1QIG RELATED DB: PDB
REMARK 900 SPECIFIC CHEMICAL AND STRUCTURAL DAMAGE AT NINE TIME
REMARK 900 POINTS (POINT D) CAUSED BY INTENSE SYNCHROTRON RADIATION
REMARK 900 TO TORPEDO CALIFORNICA ACETYLCHOLINESTERASE
REMARK 900 RELATED ID: 1QIH RELATED DB: PDB
REMARK 900 SPECIFIC CHEMICAL AND STRUCTURAL DAMAGE AT NINE TIME
REMARK 900 POINTS (POINT E) CAUSED BY INTENSE SYNCHROTRON RADIATION
REMARK 900 TO TORPEDO CALIFORNICA ACETYLCHOLINESTERASE
REMARK 900 RELATED ID: 1QII RELATED DB: PDB
REMARK 900 SPECIFIC CHEMICAL AND STRUCTURAL DAMAGE AT NINE TIME
REMARK 900 POINTS (POINT F) CAUSED BY INTENSE SYNCHROTRON RADIATION
REMARK 900 TO TORPEDO CALIFORNICA ACETYLCHOLINESTERASE
REMARK 900 RELATED ID: 1QIJ RELATED DB: PDB
REMARK 900 SPECIFIC CHEMICAL AND STRUCTURAL DAMAGE AT NINE TIME
REMARK 900 POINTS (POINT G) CAUSED BY INTENSE SYNCHROTRON RADIATION
REMARK 900 TO TORPEDO CALIFORNICA ACETYLCHOLINESTERASE
REMARK 900 RELATED ID: 1QIK RELATED DB: PDB
REMARK 900 SPECIFIC CHEMICAL AND STRUCTURAL DAMAGE AT NINE TIME
REMARK 900 POINTS (POINT H) CAUSED BY INTENSE SYNCHROTRON RADIATION
REMARK 900 TO TORPEDO CALIFORNICA ACETYLCHOLINESTERASE
REMARK 900 RELATED ID: 1QIM RELATED DB: PDB
REMARK 900 SPECIFIC CHEMICAL AND STRUCTURAL DAMAGE AT NINE TIME
REMARK 900 POINTS (POINT I) CAUSED BY INTENSE SYNCHROTRON RADIATION
REMARK 900 TO TORPEDO CALIFORNICA ACETYLCHOLINESTERASE
REMARK 900 RELATED ID: 1QID RELATED DB: PDB
REMARK 900 SPECIFIC CHEMICAL AND STRUCTURAL DAMAGE AT NINE TIME
REMARK 900 POINTS (POINT A) CAUSED BY INTENSE SYNCHROTRON RADIATION
REMARK 900 TO TORPEDO CALIFORNICA ACETYLCHOLINESTERASE
REMARK 900 RELATED ID: 1QIE RELATED DB: PDB
REMARK 900 SPECIFIC CHEMICAL AND STRUCTURAL DAMAGE AT NINE TIME
REMARK 900 POINTS (POINT B) CAUSED BY INTENSE SYNCHROTRON RADIATION
REMARK 900 TO TORPEDO CALIFORNICA ACETYLCHOLINESTERASE
REMARK 900 RELATED ID: 1QIF RELATED DB: PDB
REMARK 900 SPECIFIC CHEMICAL AND STRUCTURAL DAMAGE AT NINE TIME
REMARK 900 POINTS (POINT C) CAUSED BY INTENSE SYNCHROTRON RADIATION
REMARK 900 TO TORPEDO CALIFORNICA ACETYLCHOLINESTERASE
REMARK 900 RELATED ID: 1OCE RELATED DB: PDB
REMARK 900 ACETYLCHOLINESTERASE COMPLEXED WITH MF268
REMARK 900 RELATED ID: 1FSS RELATED DB: PDB
REMARK 900 ACETYLCHOLINESTERASE COMPLEXED WITH FASCICULIN-II
REMARK 900 RELATED ID: 1EVE RELATED DB: PDB
REMARK 900 THREE DIMENSIONAL STRUCTURE OF THE ANTI-ALZHEIMER DRUG,
REMARK 900 E2020 (ARICEPT), COMPLEXED WITH ITS TARGET
REMARK 900 ACETYLCHOLINESTERASE
REMARK 900 RELATED ID: 1EEA RELATED DB: PDB
REMARK 900 ACETYLCHOLINESTERASE
REMARK 900 RELATED ID: 1DX6 RELATED DB: PDB
REMARK 900 STRUCTURE OF ACETYLCHOLINESTERASE COMPLEXED WITH
REMARK 900 (-)-GALANTHAMINE AT 2.3A RESOLUTION
REMARK 900 RELATED ID: 1CFJ RELATED DB: PDB
REMARK 900 METHYLPHOSPHONYLATED ACETYLCHOLINESTERASE (AGED)
REMARK 900 OBTAINED BY REACTION WITH
REMARK 900 O-ISOPROPYLMETHYLPHOSPHONOFLUORIDATE (GB, SARIN)
REMARK 900 RELATED ID: 1AX9 RELATED DB: PDB
REMARK 900 ACETYLCHOLINESTERASE COMPLEXED WITH EDROPHONIUM, LAUE
REMARK 900 DATA
REMARK 900 RELATED ID: 1AMN RELATED DB: PDB
REMARK 900 TRANSITION STATE ANALOG: ACETYLCHOLINESTERASE COMPLEXED
REMARK 900 WITH M-(N,N,N-TRIMETHYLAMMONIO)TRIFLUOROACETOPHENONE
REMARK 900 RELATED ID: 1E3Q RELATED DB: PDB
REMARK 900 TORPEDO CALIFORNICA ACETYLCHOLINESTERASE COMPLEXED WITH
REMARK 900 BW284C51
REMARK 900 RELATED ID: 4ACE RELATED DB: PDB
REMARK 900 THEORETICAL MODEL OF (S)-E2020 BOUND ACETYLCHOLINESTERASE
REMARK 900 COMPLEX, 3 STRUCTURES
REMARK 900 RELATED ID: 1ACJ RELATED DB: PDB
REMARK 900 ACETYLCHOLINESTERASE (E.C.3.1.1.7) COMPLEXED WITH
REMARK 900 TACRINE
REMARK 900 RELATED ID: 1ACL RELATED DB: PDB
REMARK 900 ACETYLCHOLINESTERASE (E.C.3.1.1.7) COMPLEXED WITH
REMARK 900 DECAMETHONIUM
DBREF 1E66 A 1 543 SWS P04058 ACES_TORCA 22 564
SEQRES 1 A 543 ASP ASP HIS SER GLU LEU LEU VAL ASN THR LYS SER GLY
SEQRES 2 A 543 LYS VAL MET GLY THR ARG VAL PRO VAL LEU SER SER HIS
SEQRES 3 A 543 ILE SER ALA PHE LEU GLY ILE PRO PHE ALA GLU PRO PRO
SEQRES 4 A 543 VAL GLY ASN MET ARG PHE ARG ARG PRO GLU PRO LYS LYS
SEQRES 5 A 543 PRO TRP SER GLY VAL TRP ASN ALA SER THR TYR PRO ASN
SEQRES 6 A 543 ASN CYS GLN GLN TYR VAL ASP GLU GLN PHE PRO GLY PHE
SEQRES 7 A 543 SER GLY SER GLU MET TRP ASN PRO ASN ARG GLU MET SER
SEQRES 8 A 543 GLU ASP CYS LEU TYR LEU ASN ILE TRP VAL PRO SER PRO
SEQRES 9 A 543 ARG PRO LYS SER THR THR VAL MET VAL TRP ILE TYR GLY
SEQRES 10 A 543 GLY GLY PHE TYR SER GLY SER SER THR LEU ASP VAL TYR
SEQRES 11 A 543 ASN GLY LYS TYR LEU ALA TYR THR GLU GLU VAL VAL LEU
SEQRES 12 A 543 VAL SER LEU SER TYR ARG VAL GLY ALA PHE GLY PHE LEU
SEQRES 13 A 543 ALA LEU HIS GLY SER GLN GLU ALA PRO GLY ASN VAL GLY
SEQRES 14 A 543 LEU LEU ASP GLN ARG MET ALA LEU GLN TRP VAL HIS ASP
SEQRES 15 A 543 ASN ILE GLN PHE PHE GLY GLY ASP PRO LYS THR VAL THR
SEQRES 16 A 543 ILE PHE GLY GLU SER ALA GLY GLY ALA SER VAL GLY MET
SEQRES 17 A 543 HIS ILE LEU SER PRO GLY SER ARG ASP LEU PHE ARG ARG
SEQRES 18 A 543 ALA ILE LEU GLN SER GLY SER PRO ASN CYS PRO TRP ALA
SEQRES 19 A 543 SER VAL SER VAL ALA GLU GLY ARG ARG ARG ALA VAL GLU
SEQRES 20 A 543 LEU GLY ARG ASN LEU ASN CYS ASN LEU ASN SER ASP GLU
SEQRES 21 A 543 GLU LEU ILE HIS CYS LEU ARG GLU LYS LYS PRO GLN GLU
SEQRES 22 A 543 LEU ILE ASP VAL GLU TRP ASN VAL LEU PRO PHE ASP SER
SEQRES 23 A 543 ILE PHE ARG PHE SER PHE VAL PRO VAL ILE ASP GLY GLU
SEQRES 24 A 543 PHE PHE PRO THR SER LEU GLU SER MET LEU ASN SER GLY
SEQRES 25 A 543 ASN PHE LYS LYS THR GLN ILE LEU LEU GLY VAL ASN LYS
SEQRES 26 A 543 ASP GLU GLY SER PHE PHE LEU LEU TYR GLY ALA PRO GLY
SEQRES 27 A 543 PHE SER LYS ASP SER GLU SER LYS ILE SER ARG GLU ASP
SEQRES 28 A 543 PHE MET SER GLY VAL LYS LEU SER VAL PRO HIS ALA ASN
SEQRES 29 A 543 ASP LEU GLY LEU ASP ALA VAL THR LEU GLN TYR THR ASP
SEQRES 30 A 543 TRP MET ASP ASP ASN ASN GLY ILE LYS ASN ARG ASP GLY
SEQRES 31 A 543 LEU ASP ASP ILE VAL GLY ASP HIS ASN VAL ILE CYS PRO
SEQRES 32 A 543 LEU MET HIS PHE VAL ASN LYS TYR THR LYS PHE GLY ASN
SEQRES 33 A 543 GLY THR TYR LEU TYR PHE PHE ASN HIS ARG ALA SER ASN
SEQRES 34 A 543 LEU VAL TRP PRO GLU TRP MET GLY VAL ILE HIS GLY TYR
SEQRES 35 A 543 GLU ILE GLU PHE VAL PHE GLY LEU PRO LEU VAL LYS GLU
SEQRES 36 A 543 LEU ASN TYR THR ALA GLU GLU GLU ALA LEU SER ARG ARG
SEQRES 37 A 543 ILE MET HIS TYR TRP ALA THR PHE ALA LYS THR GLY ASN
SEQRES 38 A 543 PRO ASN GLU PRO HIS SER GLN GLU SER LYS TRP PRO LEU
SEQRES 39 A 543 PHE THR THR LYS GLU GLN LYS PHE ILE ASP LEU ASN THR
SEQRES 40 A 543 GLU PRO MET LYS VAL HIS GLN ARG LEU ARG VAL GLN MET
SEQRES 41 A 543 CYS VAL PHE TRP ASN GLN PHE LEU PRO LYS LEU LEU ASN
SEQRES 42 A 543 ALA THR ALA CYS ASP GLY GLU LEU SER SER
HET NAG A 801 14
HET NAG A 802 14
HET HUX A 803 21
HETNAM HUX 3-CHLORO-9-ETHYL-6,7,8,9,10,11-HEXAHYDRO-7,11-
HETNAM 2 HUX METHANOCYCLOOCTA[B]QUINOLIN-12-AMINE
HETNAM NAG N-ACETYL-D-GLUCOSAMINE
HETSYN HUX (-)-HUPRINE X
FORMUL 2 HUX C18 H19 N2 CL1
FORMUL 3 NAG 2(C8 H15 N1 O6)
FORMUL 2 HOH *497(H2 O1)
HELIX 1 1 VAL A 40 ARG A 44 5 5
HELIX 2 2 PHE A 78 MET A 83 1 6
HELIX 3 3 LEU A 127 ASN A 131 5 5
HELIX 4 4 GLY A 132 GLU A 140 1 9
HELIX 5 5 VAL A 150 LEU A 156 1 7
HELIX 6 6 ASN A 167 ILE A 184 1 18
HELIX 7 7 GLN A 185 PHE A 187 5 3
HELIX 8 8 SER A 200 SER A 212 1 13
HELIX 9 9 SER A 215 PHE A 219 5 5
HELIX 10 10 VAL A 238 LEU A 252 1 15
HELIX 11 11 SER A 258 LYS A 269 1 12
HELIX 12 12 LYS A 270 GLU A 278 1 9
HELIX 13 13 TRP A 279 LEU A 282 5 4
HELIX 14 14 SER A 304 GLY A 312 1 9
HELIX 15 15 GLY A 328 ALA A 336 1 9
HELIX 16 16 SER A 348 VAL A 360 1 13
HELIX 17 17 ASN A 364 THR A 376 1 13
HELIX 18 18 ASN A 383 VAL A 400 1 18
HELIX 19 19 VAL A 400 GLY A 415 1 16
HELIX 20 20 PRO A 433 GLY A 437 5 5
HELIX 21 21 GLU A 443 PHE A 448 1 6
HELIX 22 22 GLY A 449 VAL A 453 5 5
HELIX 23 23 VAL A 453 ASN A 457 5 5
HELIX 24 24 THR A 459 GLY A 480 1 22
HELIX 25 25 ARG A 517 GLN A 526 1 10
HELIX 26 26 GLN A 526 THR A 535 1 10
SHEET 1 A 3 LEU A 7 THR A 10 0
SHEET 2 A 3 GLY A 13 MET A 16 -1 O GLY A 13 N THR A 10
SHEET 3 A 3 VAL A 57 ASN A 59 1 O TRP A 58 N MET A 16
SHEET 1 B11 THR A 18 VAL A 22 0
SHEET 2 B11 SER A 25 PRO A 34 -1 O SER A 25 N VAL A 22
SHEET 3 B11 TYR A 96 VAL A 101 -1 O LEU A 97 N ILE A 33
SHEET 4 B11 VAL A 142 SER A 145 -1 O LEU A 143 N TRP A 100
SHEET 5 B11 THR A 109 ILE A 115 1 O THR A 110 N VAL A 142
SHEET 6 B11 GLY A 189 GLU A 199 1 N ASP A 190 O THR A 109
SHEET 7 B11 ARG A 221 GLN A 225 1 O ARG A 221 N ILE A 196
SHEET 8 B11 GLN A 318 ASN A 324 1 O GLN A 318 N ALA A 222
SHEET 9 B11 GLY A 417 PHE A 423 1 O GLY A 417 N ILE A 319
SHEET 10 B11 LYS A 501 LEU A 505 1 O ILE A 503 N PHE A 422
SHEET 11 B11 VAL A 512 GLN A 514 -1 O HIS A 513 N PHE A 502
SHEET 1 C 2 VAL A 236 SER A 237 0
SHEET 2 C 2 VAL A 295 ILE A 296 1 N ILE A 296 O VAL A 236
SSBOND 1 CYS A 67 CYS A 94 1555 1555
SSBOND 2 CYS A 254 CYS A 265 1555 1555
SSBOND 3 CYS A 402 CYS A 521 1555 1555
LINK ND2 ASN A 59 C1 NAG A 801 1555 1555
LINK ND2 ASN A 416 C1 NAG A 802 1555 1555
CISPEP 1 SER A 103 PRO A 104 0 0.11
SITE 1 HUX 11 TRP A 84 GLY A 118 GLY A 119 TYR A 121
SITE 2 HUX 11 GLU A 199 SER A 200 PHE A 330 TRP A 432
SITE 3 HUX 11 MET A 436 HIS A 440 HOH Z 92
CRYST1 112.335 112.335 138.165 90.00 90.00 120.00 P 31 2 1 6
ORIGX1 1.000000 0.000000 0.000000 0.00000
ORIGX2 0.000000 1.000000 0.000000 0.00000
ORIGX3 0.000000 0.000000 1.000000 0.00000
SCALE1 0.008902 0.005139 0.000000 0.00000
SCALE2 0.000000 0.010279 0.000000 0.00000
SCALE3 0.000000 0.000000 0.007238 0.00000
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