longtext: 6fse-pdb

content
HEADER    PROTEIN BINDING                         19-FEB-18   6FSE
TITLE     MUS MUSCULUS ACETYLCHOLINESTERASE IN COMPLEX WITH 1-(4-(4-
TITLE    2 ETHYLPIPERAZIN-1-YL)PIPERIDIN-1-YL)-2-((4'-METHOXY-[1,1'-BIPHENYL]-4-
TITLE    3 YL)OXY)ETHANONE DIHYDROCHLORIDE (15)
COMPND    MOL_ID: 1;
COMPND   2 MOLECULE: ACETYLCHOLINESTERASE;
COMPND   3 CHAIN: A, B;
COMPND   4 SYNONYM: ACHE;
COMPND   5 EC: 3.1.1.7;
COMPND   6 ENGINEERED: YES
SOURCE    MOL_ID: 1;
SOURCE   2 ORGANISM_SCIENTIFIC: MUS MUSCULUS;
SOURCE   3 ORGANISM_COMMON: MOUSE;
SOURCE   4 ORGANISM_TAXID: 10090;
SOURCE   5 GENE: ACHE;
SOURCE   6 EXPRESSION_SYSTEM: HOMO SAPIENS;
SOURCE   7 EXPRESSION_SYSTEM_TAXID: 9606;
SOURCE   8 EXPRESSION_SYSTEM_CELL_LINE: HEK293F
KEYWDS    INHIBITOR, HYDROLASE, ACETYLCHOLINESTERASE, PROTEIN BINDING
EXPDTA    X-RAY DIFFRACTION
AUTHOR    S.KNUTSSON,C.ENGDAHL,R.KUMARI,T.KINDAHL,N.FORSGREN,C.LINDGREN,
AUTHOR   2 S.KITUR,L.KAMAU,F.EKSTROM,A.LINUSSON
REVDAT   1   31-OCT-18 6FSE    0
JRNL        AUTH   S.KNUTSSON,C.ENGDAHL,R.KUMARI,N.FORSGREN,C.LINDGREN,
JRNL        AUTH 2 T.KINDAHL,S.KITUR,L.WACHIRA,L.KAMAU,F.J.EKSTROM,A.LINUSSON
JRNL        TITL   NON-COVALENT INHIBITORS OF MOSQUITO ACETYLCHOLINESTERASE 1
JRNL        TITL 2 WITH RESISTANCE-BREAKING POTENCY.
JRNL        REF    J. MED. CHEM.                              2018
JRNL        REFN                   ISSN 1520-4804
JRNL        PMID   30339371
JRNL        DOI    10.1021/ACS.JMEDCHEM.8B01060
REMARK   2
REMARK   2 RESOLUTION.    2.70 ANGSTROMS.
REMARK   3
REMARK   3 REFINEMENT.
REMARK   3   PROGRAM     : PHENIX (1.10.1_2155: ???)
REMARK   3   AUTHORS     : PAUL ADAMS,PAVEL AFONINE,VINCENT CHEN,IAN
REMARK   3               : DAVIS,KRESHNA GOPAL,RALF GROSSE-KUNSTLEVE,
REMARK   3               : LI-WEI HUNG,ROBERT IMMORMINO,TOM IOERGER,
REMARK   3               : AIRLIE MCCOY,ERIK MCKEE,NIGEL MORIARTY,
REMARK   3               : REETAL PAI,RANDY READ,JANE RICHARDSON,
REMARK   3               : DAVID RICHARDSON,TOD ROMO,JIM SACCHETTINI,
REMARK   3               : NICHOLAS SAUTER,JACOB SMITH,LAURENT
REMARK   3               : STORONI,TOM TERWILLIGER,PETER ZWART
REMARK   3
REMARK   3    REFINEMENT TARGET : ML
REMARK   3
REMARK   3  DATA USED IN REFINEMENT.
REMARK   3   RESOLUTION RANGE HIGH (ANGSTROMS) : 2.70
REMARK   3   RESOLUTION RANGE LOW  (ANGSTROMS) : 46.13
REMARK   3   MIN(FOBS/SIGMA_FOBS)              : 1.340
REMARK   3   COMPLETENESS FOR RANGE        (%) : 99.2
REMARK   3   NUMBER OF REFLECTIONS             : 55910
REMARK   3
REMARK   3  FIT TO DATA USED IN REFINEMENT.
REMARK   3   R VALUE     (WORKING + TEST SET) : 0.204
REMARK   3   R VALUE            (WORKING SET) : 0.204
REMARK   3   FREE R VALUE                     : 0.243
REMARK   3   FREE R VALUE TEST SET SIZE   (%) : 1.960
REMARK   3   FREE R VALUE TEST SET COUNT      : 1094
REMARK   3
REMARK   3  FIT TO DATA USED IN REFINEMENT (IN BINS).
REMARK   3   BIN  RESOLUTION RANGE  COMPL.    NWORK NFREE   RWORK  RFREE
REMARK   3     1 46.1380 -  5.3975    0.99     7148   143  0.1960 0.2319
REMARK   3     2  5.3975 -  4.2852    0.99     6913   135  0.1752 0.1883
REMARK   3     3  4.2852 -  3.7438    1.00     6888   135  0.1734 0.2030
REMARK   3     4  3.7438 -  3.4016    0.99     6788   141  0.2019 0.2295
REMARK   3     5  3.4016 -  3.1578    1.00     6818   126  0.2333 0.3003
REMARK   3     6  3.1578 -  2.9717    0.99     6775   146  0.2424 0.2765
REMARK   3     7  2.9717 -  2.8229    0.99     6730   136  0.2632 0.3412
REMARK   3     8  2.8229 -  2.7000    0.99     6756   132  0.2721 0.3741
REMARK   3
REMARK   3  BULK SOLVENT MODELLING.
REMARK   3   METHOD USED        : FLAT BULK SOLVENT MODEL
REMARK   3   SOLVENT RADIUS     : 1.11
REMARK   3   SHRINKAGE RADIUS   : 0.90
REMARK   3   K_SOL              : NULL
REMARK   3   B_SOL              : NULL
REMARK   3
REMARK   3  ERROR ESTIMATES.
REMARK   3   COORDINATE ERROR (MAXIMUM-LIKELIHOOD BASED)     : 0.360
REMARK   3   PHASE ERROR (DEGREES, MAXIMUM-LIKELIHOOD BASED) : 27.630
REMARK   3
REMARK   3  B VALUES.
REMARK   3   FROM WILSON PLOT           (A**2) : 51.23
REMARK   3   MEAN B VALUE      (OVERALL, A**2) : NULL
REMARK   3   OVERALL ANISOTROPIC B VALUE.
REMARK   3    B11 (A**2) : NULL
REMARK   3    B22 (A**2) : NULL
REMARK   3    B33 (A**2) : NULL
REMARK   3    B12 (A**2) : NULL
REMARK   3    B13 (A**2) : NULL
REMARK   3    B23 (A**2) : NULL
REMARK   3
REMARK   3  TWINNING INFORMATION.
REMARK   3   FRACTION: NULL
REMARK   3   OPERATOR: NULL
REMARK   3
REMARK   3  DEVIATIONS FROM IDEAL VALUES.
REMARK   3                 RMSD          COUNT
REMARK   3   BOND      :  0.005           8697
REMARK   3   ANGLE     :  0.606          11872
REMARK   3   CHIRALITY :  0.045           1268
REMARK   3   PLANARITY :  0.005           1554
REMARK   3   DIHEDRAL  : 15.109           5122
REMARK   3
REMARK   3  TLS DETAILS
REMARK   3   NUMBER OF TLS GROUPS  : NULL
REMARK   3
REMARK   3  NCS DETAILS
REMARK   3   NUMBER OF NCS GROUPS : NULL
REMARK   3
REMARK   3  OTHER REFINEMENT REMARKS: NULL
REMARK   4
REMARK   4 6FSE COMPLIES WITH FORMAT V. 3.30, 13-JUL-11
REMARK 100
REMARK 100 THIS ENTRY HAS BEEN PROCESSED BY PDBE ON 20-FEB-18.
REMARK 100 THE DEPOSITION ID IS D_1200008548.
REMARK 200
REMARK 200 EXPERIMENTAL DETAILS
REMARK 200  EXPERIMENT TYPE                : X-RAY DIFFRACTION
REMARK 200  DATE OF DATA COLLECTION        : 08-NOV-16
REMARK 200  TEMPERATURE           (KELVIN) : 273.15
REMARK 200  PH                             : 6.8-7.4
REMARK 200  NUMBER OF CRYSTALS USED        : 1
REMARK 200
REMARK 200  SYNCHROTRON              (Y/N) : Y
REMARK 200  RADIATION SOURCE               : BESSY
REMARK 200  BEAMLINE                       : 14.3
REMARK 200  X-RAY GENERATOR MODEL          : NULL
REMARK 200  MONOCHROMATIC OR LAUE    (M/L) : M
REMARK 200  WAVELENGTH OR RANGE        (A) : 0.9184
REMARK 200  MONOCHROMATOR                  : RAYONIX SX-165
REMARK 200  OPTICS                         : NULL
REMARK 200
REMARK 200  DETECTOR TYPE                  : CCD
REMARK 200  DETECTOR MANUFACTURER          : RAYONIX SX-165MM
REMARK 200  INTENSITY-INTEGRATION SOFTWARE : XDS
REMARK 200  DATA SCALING SOFTWARE          : SCALA
REMARK 200
REMARK 200  NUMBER OF UNIQUE REFLECTIONS   : 55911
REMARK 200  RESOLUTION RANGE HIGH      (A) : 2.700
REMARK 200  RESOLUTION RANGE LOW       (A) : 46.131
REMARK 200  REJECTION CRITERIA  (SIGMA(I)) : NULL
REMARK 200
REMARK 200 OVERALL.
REMARK 200  COMPLETENESS FOR RANGE     (%) : 99.0
REMARK 200  DATA REDUNDANCY                : 6.600
REMARK 200  R MERGE                    (I) : 0.09840
REMARK 200  R SYM                      (I) : NULL
REMARK 200   FOR THE DATA SET  : 14.6000
REMARK 200
REMARK 200 IN THE HIGHEST RESOLUTION SHELL.
REMARK 200  HIGHEST RESOLUTION SHELL, RANGE HIGH (A) : 2.70
REMARK 200  HIGHEST RESOLUTION SHELL, RANGE LOW  (A) : 2.80
REMARK 200  COMPLETENESS FOR SHELL     (%) : 99.0
REMARK 200  DATA REDUNDANCY IN SHELL       : 6.70
REMARK 200  R MERGE FOR SHELL          (I) : 0.60020
REMARK 200  R SYM FOR SHELL            (I) : NULL
REMARK 200   FOR SHELL         : 3.130
REMARK 200
REMARK 200 DIFFRACTION PROTOCOL: SINGLE WAVELENGTH
REMARK 200 METHOD USED TO DETERMINE THE STRUCTURE: FOURIER SYNTHESIS
REMARK 200 SOFTWARE USED: NULL
REMARK 200 STARTING MODEL: 1J06
REMARK 200
REMARK 200 REMARK: NULL
REMARK 280
REMARK 280 CRYSTAL
REMARK 280 SOLVENT CONTENT, VS   (%): 66.69
REMARK 280 MATTHEWS COEFFICIENT, VM (ANGSTROMS**3/DA): 3.69
REMARK 280
REMARK 280 CRYSTALLIZATION CONDITIONS: PEG 750, HEPES BUFFER, VAPOR
REMARK 280  DIFFUSION, HANGING DROP, TEMPERATURE 277.15K
REMARK 290
REMARK 290 CRYSTALLOGRAPHIC SYMMETRY
REMARK 290 SYMMETRY OPERATORS FOR SPACE GROUP: P 21 21 21
REMARK 290
REMARK 290      SYMOP   SYMMETRY
REMARK 290     NNNMMM   OPERATOR
REMARK 290       1555   X,Y,Z
REMARK 290       2555   -X+1/2,-Y,Z+1/2
REMARK 290       3555   -X,Y+1/2,-Z+1/2
REMARK 290       4555   X+1/2,-Y+1/2,-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 -1.000000  0.000000  0.000000       39.76250
REMARK 290   SMTRY2   2  0.000000 -1.000000  0.000000        0.00000
REMARK 290   SMTRY3   2  0.000000  0.000000  1.000000      113.26750
REMARK 290   SMTRY1   3 -1.000000  0.000000  0.000000        0.00000
REMARK 290   SMTRY2   3  0.000000  1.000000  0.000000       55.94250
REMARK 290   SMTRY3   3  0.000000  0.000000 -1.000000      113.26750
REMARK 290   SMTRY1   4  1.000000  0.000000  0.000000       39.76250
REMARK 290   SMTRY2   4  0.000000 -1.000000  0.000000       55.94250
REMARK 290   SMTRY3   4  0.000000  0.000000 -1.000000        0.00000
REMARK 290
REMARK 290 REMARK: NULL
REMARK 300
REMARK 300 BIOMOLECULE: 1
REMARK 300 SEE REMARK 350 FOR THE AUTHOR PROVIDED AND/OR PROGRAM
REMARK 300 GENERATED ASSEMBLY INFORMATION FOR THE STRUCTURE IN
REMARK 300 THIS ENTRY. THE REMARK MAY ALSO PROVIDE INFORMATION ON
REMARK 300 BURIED SURFACE AREA.
REMARK 350
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 SOFTWARE DETERMINED QUATERNARY STRUCTURE: DIMERIC
REMARK 350 SOFTWARE USED: PISA
REMARK 350 TOTAL BURIED SURFACE AREA: 3630 ANGSTROM**2
REMARK 350 SURFACE AREA OF THE COMPLEX: 37510 ANGSTROM**2
REMARK 350 CHANGE IN SOLVENT FREE ENERGY: 12.0 KCAL/MOL
REMARK 350 APPLY THE FOLLOWING TO CHAINS: A, B
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 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     PRO A   258
REMARK 465     PRO A   259
REMARK 465     GLY A   260
REMARK 465     GLY A   261
REMARK 465     ALA A   262
REMARK 465     GLY A   263
REMARK 465     GLY A   264
REMARK 465     THR A   543
REMARK 465     ALA A   544
REMARK 465     THR A   545
REMARK 465     GLY A   546
REMARK 465     ALA A   547
REMARK 465     PRO A   548
REMARK 465     GLU B     1
REMARK 465     GLY B     2
REMARK 465     ARG B     3
REMARK 465     PRO B   258
REMARK 465     PRO B   259
REMARK 465     GLY B   260
REMARK 465     GLY B   261
REMARK 465     ALA B   262
REMARK 465     GLY B   263
REMARK 465     GLY B   264
REMARK 465     ALA B   544
REMARK 465     THR B   545
REMARK 465     GLY B   546
REMARK 465     ALA B   547
REMARK 465     PRO B   548
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     LYS A 496    CG   CD   CE   NZ
REMARK 470     ARG B 493    CG   CD   NE   CZ   NH1  NH2
REMARK 470     LYS B 496    CG   CD   CE   NZ
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   NH2  ARG B   356     OG1  THR B   383              2.12
REMARK 500   O    VAL B   255     NH1  ARG B   276              2.19
REMARK 500
REMARK 500 REMARK: NULL
REMARK 500
REMARK 500 GEOMETRY AND STEREOCHEMISTRY
REMARK 500 SUBTOPIC: TORSION ANGLES
REMARK 500
REMARK 500 TORSION ANGLES OUTSIDE THE EXPECTED RAMACHANDRAN REGIONS:
REMARK 500 (M=MODEL NUMBER; RES=RESIDUE NAME; C=CHAIN IDENTIFIER;
REMARK 500 SSEQ=SEQUENCE NUMBER; I=INSERTION CODE).
REMARK 500
REMARK 500 STANDARD TABLE:
REMARK 500 FORMAT:(10X,I3,1X,A3,1X,A1,I4,A1,4X,F7.2,3X,F7.2)
REMARK 500
REMARK 500 EXPECTED VALUES: GJ KLEYWEGT AND TA JONES (1996). PHI/PSI-
REMARK 500 CHOLOGY: RAMACHANDRAN REVISITED. STRUCTURE 4, 1395 - 1400
REMARK 500
REMARK 500  M RES CSSEQI        PSI       PHI
REMARK 500    PHE A  47       -3.53     72.88
REMARK 500    ALA A  62       56.74   -111.91
REMARK 500    CYS A  96       -0.31   -145.59
REMARK 500    ALA A 167       71.14   -151.74
REMARK 500    SER A 203     -121.49     58.70
REMARK 500    ASP A 306      -81.49   -135.52
REMARK 500    VAL A 367       74.66   -118.45
REMARK 500    VAL A 407      -64.92   -126.37
REMARK 500    ASP A 494       97.61   -165.96
REMARK 500    SER A 541       44.14    -89.60
REMARK 500    ALA B  62       58.30   -109.21
REMARK 500    ALA B 167       74.63   -150.28
REMARK 500    SER B 203     -124.00     58.21
REMARK 500    ASP B 306      -81.81   -108.01
REMARK 500    VAL B 367       73.84   -119.80
REMARK 500    HIS B 387       68.02   -119.17
REMARK 500    VAL B 407      -64.56   -123.00
REMARK 500    HIS B 447      109.12    -58.05
REMARK 500    ARG B 493      -80.39    -92.39
REMARK 500    SER B 495      -89.17    -63.31
REMARK 500    LYS B 496      147.51     71.06
REMARK 500    LEU B 539      -60.85    159.07
REMARK 500    LEU B 540       73.12    -66.16
REMARK 500    SER B 541      -40.51    170.28
REMARK 500
REMARK 500 REMARK: NULL
REMARK 500
REMARK 500 GEOMETRY AND STEREOCHEMISTRY
REMARK 500 SUBTOPIC: NON-CIS, NON-TRANS
REMARK 500
REMARK 500 THE FOLLOWING PEPTIDE BONDS DEVIATE SIGNIFICANTLY FROM BOTH
REMARK 500 CIS AND TRANS CONFORMATION.  CIS BONDS, IF ANY, ARE LISTED
REMARK 500 ON CISPEP RECORDS.  TRANS IS DEFINED AS 180 +/- 30 AND
REMARK 500 CIS IS DEFINED AS 0 +/- 30 DEGREES.
REMARK 500                                 MODEL     OMEGA
REMARK 500 ASP A  323     LEU A  324                 -149.78
REMARK 500
REMARK 500 REMARK: NULL
REMARK 610
REMARK 610 MISSING HETEROATOM
REMARK 610 THE FOLLOWING RESIDUES HAVE MISSING ATOMS (M=MODEL NUMBER;
REMARK 610 RES=RESIDUE NAME; C=CHAIN IDENTIFIER; SSEQ=SEQUENCE NUMBER;
REMARK 610 I=INSERTION CODE):
REMARK 610   M RES C SSEQI
REMARK 610     E5K A  601
REMARK 610     PEG A  603
REMARK 610     E5K B  602
REMARK 800
REMARK 800 SITE
REMARK 800 SITE_IDENTIFIER: AC1
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: binding site for residue E5K A 601
REMARK 800
REMARK 800 SITE_IDENTIFIER: AC2
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: binding site for residue 1PG A 602
REMARK 800
REMARK 800 SITE_IDENTIFIER: AC3
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: binding site for residue PEG A 603
REMARK 800
REMARK 800 SITE_IDENTIFIER: AC4
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: binding site for residue PG0 A 604
REMARK 800
REMARK 800 SITE_IDENTIFIER: AC5
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: binding site for residue PG0 A 605
REMARK 800
REMARK 800 SITE_IDENTIFIER: AC6
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: binding site for residue PG0 B 601
REMARK 800
REMARK 800 SITE_IDENTIFIER: AC7
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: binding site for residue E5K B 602
DBREF  6FSE A    1   543  UNP    P21836   ACES_MOUSE      32    574
DBREF  6FSE B    1   543  UNP    P21836   ACES_MOUSE      32    574
SEQADV 6FSE ALA A  544  UNP  P21836              EXPRESSION TAG
SEQADV 6FSE THR A  545  UNP  P21836              EXPRESSION TAG
SEQADV 6FSE GLY A  546  UNP  P21836              EXPRESSION TAG
SEQADV 6FSE ALA A  547  UNP  P21836              EXPRESSION TAG
SEQADV 6FSE PRO A  548  UNP  P21836              EXPRESSION TAG
SEQADV 6FSE ALA B  544  UNP  P21836              EXPRESSION TAG
SEQADV 6FSE THR B  545  UNP  P21836              EXPRESSION TAG
SEQADV 6FSE GLY B  546  UNP  P21836              EXPRESSION TAG
SEQADV 6FSE ALA B  547  UNP  P21836              EXPRESSION TAG
SEQADV 6FSE PRO B  548  UNP  P21836              EXPRESSION TAG
SEQRES   1 A  548  GLU GLY ARG GLU ASP PRO GLN LEU LEU VAL ARG VAL ARG
SEQRES   2 A  548  GLY GLY GLN LEU ARG GLY ILE ARG LEU LYS ALA PRO GLY
SEQRES   3 A  548  GLY PRO VAL SER ALA PHE LEU GLY ILE PRO PHE ALA GLU
SEQRES   4 A  548  PRO PRO VAL GLY SER ARG ARG PHE MET PRO PRO GLU PRO
SEQRES   5 A  548  LYS ARG PRO TRP SER GLY VAL LEU ASP ALA THR THR PHE
SEQRES   6 A  548  GLN ASN VAL CYS TYR GLN TYR VAL ASP THR LEU TYR PRO
SEQRES   7 A  548  GLY PHE GLU GLY THR GLU MET TRP ASN PRO ASN ARG GLU
SEQRES   8 A  548  LEU SER GLU ASP CYS LEU TYR LEU ASN VAL TRP THR PRO
SEQRES   9 A  548  TYR PRO ARG PRO ALA SER PRO THR PRO VAL LEU ILE TRP
SEQRES  10 A  548  ILE TYR GLY GLY GLY PHE TYR SER GLY ALA ALA SER LEU
SEQRES  11 A  548  ASP VAL TYR ASP GLY ARG PHE LEU ALA GLN VAL GLU GLY
SEQRES  12 A  548  ALA VAL LEU VAL SER MET ASN TYR ARG VAL GLY THR PHE
SEQRES  13 A  548  GLY PHE LEU ALA LEU PRO GLY SER ARG GLU ALA PRO GLY
SEQRES  14 A  548  ASN VAL GLY LEU LEU ASP GLN ARG LEU ALA LEU GLN TRP
SEQRES  15 A  548  VAL GLN GLU ASN ILE ALA ALA PHE GLY GLY ASP PRO MET
SEQRES  16 A  548  SER VAL THR LEU PHE GLY GLU SER ALA GLY ALA ALA SER
SEQRES  17 A  548  VAL GLY MET HIS ILE LEU SER LEU PRO SER ARG SER LEU
SEQRES  18 A  548  PHE HIS ARG ALA VAL LEU GLN SER GLY THR PRO ASN GLY
SEQRES  19 A  548  PRO TRP ALA THR VAL SER ALA GLY GLU ALA ARG ARG ARG
SEQRES  20 A  548  ALA THR LEU LEU ALA ARG LEU VAL GLY CYS PRO PRO GLY
SEQRES  21 A  548  GLY ALA GLY GLY ASN ASP THR GLU LEU ILE ALA CYS LEU
SEQRES  22 A  548  ARG THR ARG PRO ALA GLN ASP LEU VAL ASP HIS GLU TRP
SEQRES  23 A  548  HIS VAL LEU PRO GLN GLU SER ILE PHE ARG PHE SER PHE
SEQRES  24 A  548  VAL PRO VAL VAL ASP GLY ASP PHE LEU SER ASP THR PRO
SEQRES  25 A  548  GLU ALA LEU ILE ASN THR GLY ASP PHE GLN ASP LEU GLN
SEQRES  26 A  548  VAL LEU VAL GLY VAL VAL LYS ASP GLU GLY SER TYR PHE
SEQRES  27 A  548  LEU VAL TYR GLY VAL PRO GLY PHE SER LYS ASP ASN GLU
SEQRES  28 A  548  SER LEU ILE SER ARG ALA GLN PHE LEU ALA GLY VAL ARG
SEQRES  29 A  548  ILE GLY VAL PRO GLN ALA SER ASP LEU ALA ALA GLU ALA
SEQRES  30 A  548  VAL VAL LEU HIS TYR THR ASP TRP LEU HIS PRO GLU ASP
SEQRES  31 A  548  PRO THR HIS LEU ARG ASP ALA MET SER ALA VAL VAL GLY
SEQRES  32 A  548  ASP HIS ASN VAL VAL CYS PRO VAL ALA GLN LEU ALA GLY
SEQRES  33 A  548  ARG LEU ALA ALA GLN GLY ALA ARG VAL TYR ALA TYR ILE
SEQRES  34 A  548  PHE GLU HIS ARG ALA SER THR LEU THR TRP PRO LEU TRP
SEQRES  35 A  548  MET GLY VAL PRO HIS GLY TYR GLU ILE GLU PHE ILE PHE
SEQRES  36 A  548  GLY LEU PRO LEU ASP PRO SER LEU ASN TYR THR THR GLU
SEQRES  37 A  548  GLU ARG ILE PHE ALA GLN ARG LEU MET LYS TYR TRP THR
SEQRES  38 A  548  ASN PHE ALA ARG THR GLY ASP PRO ASN ASP PRO ARG ASP
SEQRES  39 A  548  SER LYS SER PRO GLN TRP PRO PRO TYR THR THR ALA ALA
SEQRES  40 A  548  GLN GLN TYR VAL SER LEU ASN LEU LYS PRO LEU GLU VAL
SEQRES  41 A  548  ARG ARG GLY LEU ARG ALA GLN THR CYS ALA PHE TRP ASN
SEQRES  42 A  548  ARG PHE LEU PRO LYS LEU LEU SER ALA THR ALA THR GLY
SEQRES  43 A  548  ALA PRO
SEQRES   1 B  548  GLU GLY ARG GLU ASP PRO GLN LEU LEU VAL ARG VAL ARG
SEQRES   2 B  548  GLY GLY GLN LEU ARG GLY ILE ARG LEU LYS ALA PRO GLY
SEQRES   3 B  548  GLY PRO VAL SER ALA PHE LEU GLY ILE PRO PHE ALA GLU
SEQRES   4 B  548  PRO PRO VAL GLY SER ARG ARG PHE MET PRO PRO GLU PRO
SEQRES   5 B  548  LYS ARG PRO TRP SER GLY VAL LEU ASP ALA THR THR PHE
SEQRES   6 B  548  GLN ASN VAL CYS TYR GLN TYR VAL ASP THR LEU TYR PRO
SEQRES   7 B  548  GLY PHE GLU GLY THR GLU MET TRP ASN PRO ASN ARG GLU
SEQRES   8 B  548  LEU SER GLU ASP CYS LEU TYR LEU ASN VAL TRP THR PRO
SEQRES   9 B  548  TYR PRO ARG PRO ALA SER PRO THR PRO VAL LEU ILE TRP
SEQRES  10 B  548  ILE TYR GLY GLY GLY PHE TYR SER GLY ALA ALA SER LEU
SEQRES  11 B  548  ASP VAL TYR ASP GLY ARG PHE LEU ALA GLN VAL GLU GLY
SEQRES  12 B  548  ALA VAL LEU VAL SER MET ASN TYR ARG VAL GLY THR PHE
SEQRES  13 B  548  GLY PHE LEU ALA LEU PRO GLY SER ARG GLU ALA PRO GLY
SEQRES  14 B  548  ASN VAL GLY LEU LEU ASP GLN ARG LEU ALA LEU GLN TRP
SEQRES  15 B  548  VAL GLN GLU ASN ILE ALA ALA PHE GLY GLY ASP PRO MET
SEQRES  16 B  548  SER VAL THR LEU PHE GLY GLU SER ALA GLY ALA ALA SER
SEQRES  17 B  548  VAL GLY MET HIS ILE LEU SER LEU PRO SER ARG SER LEU
SEQRES  18 B  548  PHE HIS ARG ALA VAL LEU GLN SER GLY THR PRO ASN GLY
SEQRES  19 B  548  PRO TRP ALA THR VAL SER ALA GLY GLU ALA ARG ARG ARG
SEQRES  20 B  548  ALA THR LEU LEU ALA ARG LEU VAL GLY CYS PRO PRO GLY
SEQRES  21 B  548  GLY ALA GLY GLY ASN ASP THR GLU LEU ILE ALA CYS LEU
SEQRES  22 B  548  ARG THR ARG PRO ALA GLN ASP LEU VAL ASP HIS GLU TRP
SEQRES  23 B  548  HIS VAL LEU PRO GLN GLU SER ILE PHE ARG PHE SER PHE
SEQRES  24 B  548  VAL PRO VAL VAL ASP GLY ASP PHE LEU SER ASP THR PRO
SEQRES  25 B  548  GLU ALA LEU ILE ASN THR GLY ASP PHE GLN ASP LEU GLN
SEQRES  26 B  548  VAL LEU VAL GLY VAL VAL LYS ASP GLU GLY SER TYR PHE
SEQRES  27 B  548  LEU VAL TYR GLY VAL PRO GLY PHE SER LYS ASP ASN GLU
SEQRES  28 B  548  SER LEU ILE SER ARG ALA GLN PHE LEU ALA GLY VAL ARG
SEQRES  29 B  548  ILE GLY VAL PRO GLN ALA SER ASP LEU ALA ALA GLU ALA
SEQRES  30 B  548  VAL VAL LEU HIS TYR THR ASP TRP LEU HIS PRO GLU ASP
SEQRES  31 B  548  PRO THR HIS LEU ARG ASP ALA MET SER ALA VAL VAL GLY
SEQRES  32 B  548  ASP HIS ASN VAL VAL CYS PRO VAL ALA GLN LEU ALA GLY
SEQRES  33 B  548  ARG LEU ALA ALA GLN GLY ALA ARG VAL TYR ALA TYR ILE
SEQRES  34 B  548  PHE GLU HIS ARG ALA SER THR LEU THR TRP PRO LEU TRP
SEQRES  35 B  548  MET GLY VAL PRO HIS GLY TYR GLU ILE GLU PHE ILE PHE
SEQRES  36 B  548  GLY LEU PRO LEU ASP PRO SER LEU ASN TYR THR THR GLU
SEQRES  37 B  548  GLU ARG ILE PHE ALA GLN ARG LEU MET LYS TYR TRP THR
SEQRES  38 B  548  ASN PHE ALA ARG THR GLY ASP PRO ASN ASP PRO ARG ASP
SEQRES  39 B  548  SER LYS SER PRO GLN TRP PRO PRO TYR THR THR ALA ALA
SEQRES  40 B  548  GLN GLN TYR VAL SER LEU ASN LEU LYS PRO LEU GLU VAL
SEQRES  41 B  548  ARG ARG GLY LEU ARG ALA GLN THR CYS ALA PHE TRP ASN
SEQRES  42 B  548  ARG PHE LEU PRO LYS LEU LEU SER ALA THR ALA THR GLY
SEQRES  43 B  548  ALA PRO
HET    E5K  A 601      25
HET    1PG  A 602      17
HET    PEG  A 603       5
HET    PG0  A 604       8
HET    PG0  A 605       8
HET    PG0  B 601       8
HET    E5K  B 602      25
HETNAM     E5K 1-[4-(4-ETHYLPIPERAZIN-1-YL)PIPERIDIN-1-YL]-2-[4-(4-
HETNAM   2 E5K  METHOXYPHENYL)PHENOXY]ETHANONE
HETNAM     1PG 2-(2-{2-[2-(2-METHOXY-ETHOXY)-ETHOXY]-ETHOXY}-ETHOXY)-
HETNAM   2 1PG  ETHANOL
HETNAM     PEG DI(HYDROXYETHYL)ETHER
HETNAM     PG0 2-(2-METHOXYETHOXY)ETHANOL
HETSYN     PG0 PEG 6000
FORMUL   3  E5K    2(C26 H35 N3 O3)
FORMUL   4  1PG    C11 H24 O6
FORMUL   5  PEG    C4 H10 O3
FORMUL   6  PG0    3(C5 H12 O3)
FORMUL  10  HOH   *168(H2 O)
HELIX    1 AA1 ASP A    5  GLN A    7  5                                   3
HELIX    2 AA2 VAL A   42  ARG A   46  5                                   5
HELIX    3 AA3 PHE A   80  MET A   85  1                                   6
HELIX    4 AA4 LEU A  130  ASP A  134  5                                   5
HELIX    5 AA5 GLY A  135  GLU A  142  1                                   8
HELIX    6 AA6 VAL A  153  LEU A  159  1                                   7
HELIX    7 AA7 ASN A  170  ILE A  187  1                                  18
HELIX    8 AA8 ALA A  188  PHE A  190  5                                   3
HELIX    9 AA9 SER A  203  SER A  215  1                                  13
HELIX   10 AB1 SER A  215  SER A  220  1                                   6
HELIX   11 AB2 SER A  240  GLY A  256  1                                  17
HELIX   12 AB3 ASP A  266  ARG A  274  1                                   9
HELIX   13 AB4 PRO A  277  GLU A  285  1                                   9
HELIX   14 AB5 TRP A  286  LEU A  289  5                                   4
HELIX   15 AB6 THR A  311  THR A  318  1                                   8
HELIX   16 AB7 SER A  336  GLY A  342  5                                   7
HELIX   17 AB8 SER A  355  VAL A  367  1                                  13
HELIX   18 AB9 SER A  371  THR A  383  1                                  13
HELIX   19 AC1 ASP A  390  VAL A  407  1                                  18
HELIX   20 AC2 VAL A  407  GLN A  421  1                                  15
HELIX   21 AC3 PRO A  440  GLY A  444  5                                   5
HELIX   22 AC4 GLU A  450  PHE A  455  1                                   6
HELIX   23 AC5 GLY A  456  ASN A  464  5                                   9
HELIX   24 AC6 THR A  466  GLY A  487  1                                  22
HELIX   25 AC7 ARG A  525  ARG A  534  1                                  10
HELIX   26 AC8 ARG A  534  LEU A  540  1                                   7
HELIX   27 AC9 ASP B    5  GLN B    7  5                                   3
HELIX   28 AD1 VAL B   42  ARG B   46  5                                   5
HELIX   29 AD2 PHE B   80  MET B   85  1                                   6
HELIX   30 AD3 LEU B  130  ASP B  134  5                                   5
HELIX   31 AD4 GLY B  135  GLU B  142  1                                   8
HELIX   32 AD5 VAL B  153  LEU B  159  1                                   7
HELIX   33 AD6 ASN B  170  ILE B  187  1                                  18
HELIX   34 AD7 ALA B  188  PHE B  190  5                                   3
HELIX   35 AD8 SER B  203  LEU B  214  1                                  12
HELIX   36 AD9 SER B  215  SER B  220  1                                   6
HELIX   37 AE1 SER B  240  VAL B  255  1                                  16
HELIX   38 AE2 ASP B  266  ARG B  274  1                                   9
HELIX   39 AE3 PRO B  277  ASP B  283  1                                   7
HELIX   40 AE4 HIS B  284  VAL B  288  5                                   5
HELIX   41 AE5 THR B  311  GLY B  319  1                                   9
HELIX   42 AE6 SER B  336  GLY B  342  5                                   7
HELIX   43 AE7 SER B  355  VAL B  367  1                                  13
HELIX   44 AE8 SER B  371  THR B  383  1                                  13
HELIX   45 AE9 ASP B  390  VAL B  407  1                                  18
HELIX   46 AF1 VAL B  407  GLN B  421  1                                  15
HELIX   47 AF2 PRO B  440  GLY B  444  5                                   5
HELIX   48 AF3 GLU B  450  PHE B  455  1                                   6
HELIX   49 AF4 GLY B  456  ASN B  464  5                                   9
HELIX   50 AF5 THR B  466  GLY B  487  1                                  22
HELIX   51 AF6 ARG B  525  ARG B  534  1                                  10
SHEET    1 AA1 3 LEU A   9  VAL A  12  0
SHEET    2 AA1 3 GLY A  15  ARG A  18 -1  O  GLY A  15   N  VAL A  12
SHEET    3 AA1 3 VAL A  59  ASP A  61  1  O  LEU A  60   N  GLN A  16
SHEET    1 AA211 ILE A  20  ALA A  24  0
SHEET    2 AA211 GLY A  27  PRO A  36 -1  O  VAL A  29   N  LEU A  22
SHEET    3 AA211 TYR A  98  PRO A 104 -1  O  VAL A 101   N  PHE A  32
SHEET    4 AA211 VAL A 145  MET A 149 -1  O  LEU A 146   N  TRP A 102
SHEET    5 AA211 THR A 112  ILE A 118  1  N  TRP A 117   O  VAL A 147
SHEET    6 AA211 GLY A 192  GLU A 202  1  O  ASP A 193   N  THR A 112
SHEET    7 AA211 ARG A 224  GLN A 228  1  O  ARG A 224   N  LEU A 199
SHEET    8 AA211 GLN A 325  VAL A 331  1  O  LEU A 327   N  LEU A 227
SHEET    9 AA211 ARG A 424  PHE A 430  1  O  PHE A 430   N  VAL A 330
SHEET   10 AA211 GLN A 509  LEU A 513  1  O  LEU A 513   N  ILE A 429
SHEET   11 AA211 GLU A 519  ARG A 522 -1  O  ARG A 521   N  TYR A 510
SHEET    1 AA3 2 VAL A  68  CYS A  69  0
SHEET    2 AA3 2 LEU A  92  SER A  93  1  O  SER A  93   N  VAL A  68
SHEET    1 AA4 3 LEU B   9  VAL B  12  0
SHEET    2 AA4 3 GLY B  15  ARG B  18 -1  O  LEU B  17   N  VAL B  10
SHEET    3 AA4 3 VAL B  59  ASP B  61  1  O  LEU B  60   N  GLN B  16
SHEET    1 AA511 ILE B  20  ALA B  24  0
SHEET    2 AA511 GLY B  27  PRO B  36 -1  O  VAL B  29   N  LEU B  22
SHEET    3 AA511 TYR B  98  PRO B 104 -1  O  LEU B  99   N  ILE B  35
SHEET    4 AA511 VAL B 145  MET B 149 -1  O  SER B 148   N  ASN B 100
SHEET    5 AA511 THR B 112  ILE B 118  1  N  TRP B 117   O  VAL B 147
SHEET    6 AA511 GLY B 192  GLU B 202  1  O  ASP B 193   N  THR B 112
SHEET    7 AA511 ARG B 224  GLN B 228  1  O  GLN B 228   N  GLY B 201
SHEET    8 AA511 GLN B 325  VAL B 331  1  O  LEU B 327   N  LEU B 227
SHEET    9 AA511 ARG B 424  PHE B 430  1  O  PHE B 430   N  VAL B 330
SHEET   10 AA511 GLN B 509  LEU B 513  1  O  LEU B 513   N  ILE B 429
SHEET   11 AA511 GLU B 519  ARG B 522 -1  O  ARG B 521   N  TYR B 510
SHEET    1 AA6 2 VAL B  68  CYS B  69  0
SHEET    2 AA6 2 LEU B  92  SER B  93  1  O  SER B  93   N  VAL B  68
SSBOND   1 CYS A   69    CYS A   96                          1555   1555  2.03
SSBOND   2 CYS A  257    CYS A  272                          1555   1555  2.03
SSBOND   3 CYS A  409    CYS A  529                          1555   1555  2.03
SSBOND   4 CYS B   69    CYS B   96                          1555   1555  2.03
SSBOND   5 CYS B  257    CYS B  272                          1555   1555  2.03
SSBOND   6 CYS B  409    CYS B  529                          1555   1555  2.03
CISPEP   1 TYR A  105    PRO A  106          0         1.55
CISPEP   2 TYR B  105    PRO B  106          0         5.36
SITE     1 AC1 12 TYR A  72  TRP A  86  GLY A 120  GLY A 121
SITE     2 AC1 12 TYR A 124  GLU A 202  TRP A 286  TYR A 337
SITE     3 AC1 12 PHE A 338  TYR A 341  PG0 A 604  HOH A 704
SITE     1 AC2 10 LEU A 380  HIS A 381  GLN A 527  PHE A 531
SITE     2 AC2 10 PHE A 535  LEU B 380  HIS B 381  GLN B 527
SITE     3 AC2 10 PHE B 531  PHE B 535
SITE     1 AC3  4 VAL A 303  ASP A 304  GLY A 305  SER A 309
SITE     1 AC4  2 TYR A  72  E5K A 601
SITE     1 AC5  3 LYS A  53  GLN A  66  TYR A  98
SITE     1 AC6  2 SER B 309  ASP B 310
SITE     1 AC7  8 TYR B  72  TYR B 124  GLU B 202  TYR B 337
SITE     2 AC7  8 PHE B 338  TYR B 341  HIS B 447  HOH B 701
CRYST1   79.525  111.885  226.535  90.00  90.00  90.00 P 21 21 21    8
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      0.012575  0.000000  0.000000        0.00000
SCALE2      0.000000  0.008938  0.000000        0.00000
SCALE3      0.000000  0.000000  0.004414        0.00000
TER    4185      ALA A 542
TER    8347      THR B 543
MASTER      344    0    7   51   32    0   12    6 8595    2  108   86
END