longtext: 7l4w-pdb

content
HEADER    HYDROLASE/INHIBITOR                     21-DEC-20   7L4W
TITLE     CRYSTAL STRUCTURE OF HUMAN MONOACYLGLYCEROL LIPASE IN COMPLEX WITH
TITLE    2 COMPOUND 2D
COMPND    MOL_ID: 1;
COMPND   2 MOLECULE: MONOGLYCERIDE LIPASE;
COMPND   3 CHAIN: A, B;
COMPND   4 ENGINEERED: YES
SOURCE    MOL_ID: 1;
SOURCE   2 ORGANISM_SCIENTIFIC: HOMO SAPIENS;
SOURCE   3 ORGANISM_COMMON: HUMAN;
SOURCE   4 ORGANISM_TAXID: 9606;
SOURCE   5 GENE: MGLL;
SOURCE   6 EXPRESSION_SYSTEM: ESCHERICHIA COLI;
SOURCE   7 EXPRESSION_SYSTEM_TAXID: 562
KEYWDS    INHIBITOR, SERINE HYDROLASE, HYDROLASE, HYDROLASE-INHIBITOR COMPLEX
EXPDTA    X-RAY DIFFRACTION
AUTHOR    L.QIN,W.LANE,R.J.SKENE
REVDAT   1   11-AUG-21 7L4W    0
JRNL        AUTH   S.IKEDA,H.SUGIYAMA,H.TOKUHARA,M.MURAKAMI,M.NAKAMURA,Y.OGURO,
JRNL        AUTH 2 J.AIDA,N.MORISHITA,S.SOGABE,D.R.DOUGAN,S.C.GAY,L.QIN,
JRNL        AUTH 3 N.ARIMURA,Y.TAKAHASHI,M.SASAKI,Y.KAMADA,K.AOYAMA,K.KIMOTO,
JRNL        AUTH 4 M.KAMATA
JRNL        TITL   DESIGN AND SYNTHESIS OF NOVEL SPIRO DERIVATIVES AS POTENT
JRNL        TITL 2 AND REVERSIBLE MONOACYLGLYCEROL LIPASE (MAGL) INHIBITORS:
JRNL        TITL 3 BIOISOSTERIC TRANSFORMATION FROM 3-OXO-3,4-DIHYDRO-2 H
JRNL        TITL 4 -BENZO[ B ][1,4]OXAZIN-6-YL MOIETY.
JRNL        REF    J.MED.CHEM.                                2021
JRNL        REFN                   ISSN 0022-2623
JRNL        PMID   34328319
JRNL        DOI    10.1021/ACS.JMEDCHEM.1C00432
REMARK   2
REMARK   2 RESOLUTION.    2.20 ANGSTROMS.
REMARK   3
REMARK   3 REFINEMENT.
REMARK   3   PROGRAM     : REFMAC 5.8.0257
REMARK   3   AUTHORS     : MURSHUDOV,SKUBAK,LEBEDEV,PANNU,STEINER,
REMARK   3               : NICHOLLS,WINN,LONG,VAGIN
REMARK   3
REMARK   3    REFINEMENT TARGET : MAXIMUM LIKELIHOOD
REMARK   3
REMARK   3  DATA USED IN REFINEMENT.
REMARK   3   RESOLUTION RANGE HIGH (ANGSTROMS) : 2.20
REMARK   3   RESOLUTION RANGE LOW  (ANGSTROMS) : 38.59
REMARK   3   DATA CUTOFF            (SIGMA(F)) : 0.000
REMARK   3   COMPLETENESS FOR RANGE        (%) : 99.2
REMARK   3   NUMBER OF REFLECTIONS             : 38970
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 + TEST SET) : 0.188
REMARK   3   R VALUE            (WORKING SET) : 0.187
REMARK   3   FREE R VALUE                     : 0.221
REMARK   3   FREE R VALUE TEST SET SIZE   (%) : 5.000
REMARK   3   FREE R VALUE TEST SET COUNT      : 2031
REMARK   3
REMARK   3  FIT IN THE HIGHEST RESOLUTION BIN.
REMARK   3   TOTAL NUMBER OF BINS USED           : NULL
REMARK   3   BIN RESOLUTION RANGE HIGH       (A) : 2.20
REMARK   3   BIN RESOLUTION RANGE LOW        (A) : 2.25
REMARK   3   REFLECTION IN BIN     (WORKING SET) : 2713
REMARK   3   BIN COMPLETENESS (WORKING+TEST) (%) : 93.53
REMARK   3   BIN R VALUE           (WORKING SET) : 0.3410
REMARK   3   BIN FREE R VALUE SET COUNT          : 122
REMARK   3   BIN FREE R VALUE                    : 0.3370
REMARK   3
REMARK   3  NUMBER OF NON-HYDROGEN ATOMS USED IN REFINEMENT.
REMARK   3   PROTEIN ATOMS            : 4457
REMARK   3   NUCLEIC ACID ATOMS       : 0
REMARK   3   HETEROGEN ATOMS          : 54
REMARK   3   SOLVENT ATOMS            : 131
REMARK   3
REMARK   3  B VALUES.
REMARK   3   FROM WILSON PLOT           (A**2) : NULL
REMARK   3   MEAN B VALUE      (OVERALL, A**2) : 61.31
REMARK   3   OVERALL ANISOTROPIC B VALUE.
REMARK   3    B11 (A**2) : 1.66000
REMARK   3    B22 (A**2) : -3.09000
REMARK   3    B33 (A**2) : 1.43000
REMARK   3    B12 (A**2) : 0.00000
REMARK   3    B13 (A**2) : 0.00000
REMARK   3    B23 (A**2) : 0.00000
REMARK   3
REMARK   3  ESTIMATED OVERALL COORDINATE ERROR.
REMARK   3   ESU BASED ON R VALUE                            (A): 0.199
REMARK   3   ESU BASED ON FREE R VALUE                       (A): 0.171
REMARK   3   ESU BASED ON MAXIMUM LIKELIHOOD                 (A): 0.170
REMARK   3   ESU FOR B VALUES BASED ON MAXIMUM LIKELIHOOD (A**2): 14.805
REMARK   3
REMARK   3 CORRELATION COEFFICIENTS.
REMARK   3   CORRELATION COEFFICIENT FO-FC      : 0.969
REMARK   3   CORRELATION COEFFICIENT FO-FC FREE : 0.961
REMARK   3
REMARK   3  RMS DEVIATIONS FROM IDEAL VALUES        COUNT    RMS    WEIGHT
REMARK   3   BOND LENGTHS REFINED ATOMS        (A):  4623 ; 0.007 ; 0.013
REMARK   3   BOND LENGTHS OTHERS               (A):  4273 ; 0.001 ; 0.017
REMARK   3   BOND ANGLES REFINED ATOMS   (DEGREES):  6290 ; 1.450 ; 1.650
REMARK   3   BOND ANGLES OTHERS          (DEGREES):  9894 ; 1.240 ; 1.566
REMARK   3   TORSION ANGLES, PERIOD 1    (DEGREES):   576 ; 6.607 ; 5.000
REMARK   3   TORSION ANGLES, PERIOD 2    (DEGREES):   218 ;30.272 ;21.651
REMARK   3   TORSION ANGLES, PERIOD 3    (DEGREES):   747 ;13.955 ;15.000
REMARK   3   TORSION ANGLES, PERIOD 4    (DEGREES):    28 ;11.367 ;15.000
REMARK   3   CHIRAL-CENTER RESTRAINTS       (A**3):   580 ; 0.065 ; 0.200
REMARK   3   GENERAL PLANES REFINED ATOMS      (A):  5159 ; 0.006 ; 0.020
REMARK   3   GENERAL PLANES OTHERS             (A):   941 ; 0.001 ; 0.020
REMARK   3   NON-BONDED CONTACTS REFINED ATOMS (A):  NULL ;  NULL ;  NULL
REMARK   3   NON-BONDED CONTACTS OTHERS        (A):  NULL ;  NULL ;  NULL
REMARK   3   NON-BONDED TORSION REFINED ATOMS  (A):  NULL ;  NULL ;  NULL
REMARK   3   NON-BONDED TORSION OTHERS         (A):  NULL ;  NULL ;  NULL
REMARK   3   H-BOND (X...Y) REFINED ATOMS      (A):  NULL ;  NULL ;  NULL
REMARK   3   H-BOND (X...Y) OTHERS             (A):  NULL ;  NULL ;  NULL
REMARK   3   POTENTIAL METAL-ION REFINED ATOMS (A):  NULL ;  NULL ;  NULL
REMARK   3   POTENTIAL METAL-ION OTHERS        (A):  NULL ;  NULL ;  NULL
REMARK   3   SYMMETRY VDW REFINED ATOMS        (A):  NULL ;  NULL ;  NULL
REMARK   3   SYMMETRY VDW OTHERS               (A):  NULL ;  NULL ;  NULL
REMARK   3   SYMMETRY H-BOND REFINED ATOMS     (A):  NULL ;  NULL ;  NULL
REMARK   3   SYMMETRY H-BOND OTHERS            (A):  NULL ;  NULL ;  NULL
REMARK   3   SYMMETRY METAL-ION REFINED ATOMS  (A):  NULL ;  NULL ;  NULL
REMARK   3   SYMMETRY METAL-ION OTHERS         (A):  NULL ;  NULL ;  NULL
REMARK   3
REMARK   3  ISOTROPIC THERMAL FACTOR RESTRAINTS.     COUNT   RMS    WEIGHT
REMARK   3   MAIN-CHAIN BOND REFINED ATOMS  (A**2):  NULL ;  NULL ;  NULL
REMARK   3   MAIN-CHAIN BOND OTHER ATOMS    (A**2):  NULL ;  NULL ;  NULL
REMARK   3   MAIN-CHAIN ANGLE REFINED ATOMS (A**2):  NULL ;  NULL ;  NULL
REMARK   3   MAIN-CHAIN ANGLE OTHER ATOMS   (A**2):  NULL ;  NULL ;  NULL
REMARK   3   SIDE-CHAIN BOND REFINED ATOMS  (A**2):  NULL ;  NULL ;  NULL
REMARK   3   SIDE-CHAIN BOND OTHER ATOMS    (A**2):  NULL ;  NULL ;  NULL
REMARK   3   SIDE-CHAIN ANGLE REFINED ATOMS (A**2):  NULL ;  NULL ;  NULL
REMARK   3   SIDE-CHAIN ANGLE OTHER ATOMS   (A**2):  NULL ;  NULL ;  NULL
REMARK   3   LONG RANGE B REFINED ATOMS     (A**2):  NULL ;  NULL ;  NULL
REMARK   3   LONG RANGE B OTHER ATOMS       (A**2):  NULL ;  NULL ;  NULL
REMARK   3
REMARK   3 ANISOTROPIC THERMAL FACTOR RESTRAINTS.    COUNT   RMS   WEIGHT
REMARK   3   RIGID-BOND RESTRAINTS          (A**2):  NULL ;  NULL ;  NULL
REMARK   3   SPHERICITY; FREE ATOMS         (A**2):  NULL ;  NULL ;  NULL
REMARK   3   SPHERICITY; BONDED ATOMS       (A**2):  NULL ;  NULL ;  NULL
REMARK   3
REMARK   3  NCS RESTRAINTS STATISTICS
REMARK   3   NUMBER OF DIFFERENT NCS GROUPS : NULL
REMARK   3
REMARK   3  TLS DETAILS
REMARK   3   NUMBER OF TLS GROUPS  : 2
REMARK   3
REMARK   3   TLS GROUP : 1
REMARK   3    NUMBER OF COMPONENTS GROUP : 2
REMARK   3    COMPONENTS        C SSSEQI   TO  C SSSEQI
REMARK   3    RESIDUE RANGE :   A     7        A   294
REMARK   3    RESIDUE RANGE :   A   401        A   401
REMARK   3    ORIGIN FOR THE GROUP (A):  -21.108  -10.810  -50.302
REMARK   3    T TENSOR
REMARK   3      T11:   0.1932 T22:   0.0282
REMARK   3      T33:   0.1553 T12:  -0.0386
REMARK   3      T13:  -0.0027 T23:  -0.0074
REMARK   3    L TENSOR
REMARK   3      L11:   0.2823 L22:   2.7232
REMARK   3      L33:   0.2227 L12:  -0.4899
REMARK   3      L13:  -0.1260 L23:  -0.3238
REMARK   3    S TENSOR
REMARK   3      S11:  -0.0708 S12:   0.0545 S13:   0.0494
REMARK   3      S21:  -0.0617 S22:   0.0798 S23:  -0.1933
REMARK   3      S31:   0.0463 S32:  -0.0731 S33:  -0.0090
REMARK   3
REMARK   3   TLS GROUP : 2
REMARK   3    NUMBER OF COMPONENTS GROUP : 2
REMARK   3    COMPONENTS        C SSSEQI   TO  C SSSEQI
REMARK   3    RESIDUE RANGE :   B     5        B   294
REMARK   3    RESIDUE RANGE :   B   401        B   401
REMARK   3    ORIGIN FOR THE GROUP (A):  -26.572   12.247  -18.183
REMARK   3    T TENSOR
REMARK   3      T11:   0.2060 T22:   0.0176
REMARK   3      T33:   0.1188 T12:   0.0363
REMARK   3      T13:   0.0817 T23:   0.0441
REMARK   3    L TENSOR
REMARK   3      L11:   0.0344 L22:   2.1142
REMARK   3      L33:   0.7986 L12:  -0.0218
REMARK   3      L13:  -0.1005 L23:  -0.5229
REMARK   3    S TENSOR
REMARK   3      S11:  -0.0649 S12:  -0.0075 S13:  -0.0244
REMARK   3      S21:   0.1131 S22:  -0.0012 S23:   0.0379
REMARK   3      S31:   0.0036 S32:   0.0055 S33:   0.0660
REMARK   3
REMARK   3  BULK SOLVENT MODELLING.
REMARK   3   METHOD USED : MASK
REMARK   3   PARAMETERS FOR MASK CALCULATION
REMARK   3   VDW PROBE RADIUS   : 1.20
REMARK   3   ION PROBE RADIUS   : 0.80
REMARK   3   SHRINKAGE RADIUS   : 0.80
REMARK   3
REMARK   3  OTHER REFINEMENT REMARKS: HYDROGENS HAVE BEEN ADDED IN THE RIDING
REMARK   3  POSITIONS U VALUES : WITH TLS ADDED
REMARK   4
REMARK   4 7L4W COMPLIES WITH FORMAT V. 3.30, 13-JUL-11
REMARK 100
REMARK 100 THIS ENTRY HAS BEEN PROCESSED BY RCSB ON 23-DEC-20.
REMARK 100 THE DEPOSITION ID IS D_1000253718.
REMARK 200
REMARK 200 EXPERIMENTAL DETAILS
REMARK 200  EXPERIMENT TYPE                : X-RAY DIFFRACTION
REMARK 200  DATE OF DATA COLLECTION        : 06-JAN-16
REMARK 200  TEMPERATURE           (KELVIN) : 100
REMARK 200  PH                             : NULL
REMARK 200  NUMBER OF CRYSTALS USED        : 1
REMARK 200
REMARK 200  SYNCHROTRON              (Y/N) : Y
REMARK 200  RADIATION SOURCE               : SSRL
REMARK 200  BEAMLINE                       : BL7-1
REMARK 200  X-RAY GENERATOR MODEL          : NULL
REMARK 200  MONOCHROMATIC OR LAUE    (M/L) : M
REMARK 200  WAVELENGTH OR RANGE        (A) : 1.0
REMARK 200  MONOCHROMATOR                  : NULL
REMARK 200  OPTICS                         : NULL
REMARK 200
REMARK 200  DETECTOR TYPE                  : CCD
REMARK 200  DETECTOR MANUFACTURER          : ADSC QUANTUM 315R
REMARK 200  INTENSITY-INTEGRATION SOFTWARE : HKL-2000
REMARK 200  DATA SCALING SOFTWARE          : HKL-2000
REMARK 200
REMARK 200  NUMBER OF UNIQUE REFLECTIONS   : 41130
REMARK 200  RESOLUTION RANGE HIGH      (A) : 2.200
REMARK 200  RESOLUTION RANGE LOW       (A) : 50.000
REMARK 200  REJECTION CRITERIA  (SIGMA(I)) : NULL
REMARK 200
REMARK 200 OVERALL.
REMARK 200  COMPLETENESS FOR RANGE     (%) : 99.8
REMARK 200  DATA REDUNDANCY                : 7.100
REMARK 200  R MERGE                    (I) : 0.06300
REMARK 200  R SYM                      (I) : NULL
REMARK 200   FOR THE DATA SET  : 9.6000
REMARK 200
REMARK 200 IN THE HIGHEST RESOLUTION SHELL.
REMARK 200  HIGHEST RESOLUTION SHELL, RANGE HIGH (A) : 2.20
REMARK 200  HIGHEST RESOLUTION SHELL, RANGE LOW  (A) : 2.24
REMARK 200  COMPLETENESS FOR SHELL     (%) : 97.1
REMARK 200  DATA REDUNDANCY IN SHELL       : 5.20
REMARK 200  R MERGE FOR SHELL          (I) : 0.98700
REMARK 200  R SYM FOR SHELL            (I) : NULL
REMARK 200   FOR SHELL         : NULL
REMARK 200
REMARK 200 DIFFRACTION PROTOCOL: SINGLE WAVELENGTH
REMARK 200 METHOD USED TO DETERMINE THE STRUCTURE: MOLECULAR REPLACEMENT
REMARK 200 SOFTWARE USED: PHASER
REMARK 200 STARTING MODEL: 5ZUN
REMARK 200
REMARK 200 REMARK: NULL
REMARK 280
REMARK 280 CRYSTAL
REMARK 280 SOLVENT CONTENT, VS   (%): 56.72
REMARK 280 MATTHEWS COEFFICIENT, VM (ANGSTROMS**3/DA): 2.84
REMARK 280
REMARK 280 CRYSTALLIZATION CONDITIONS: 0.1M NAOAC PH 5.5, 32-38% MPD, VAPOR
REMARK 280  DIFFUSION, SITTING DROP, TEMPERATURE 293K
REMARK 290
REMARK 290 CRYSTALLOGRAPHIC SYMMETRY
REMARK 290 SYMMETRY OPERATORS FOR SPACE GROUP: I 2 2 2
REMARK 290
REMARK 290      SYMOP   SYMMETRY
REMARK 290     NNNMMM   OPERATOR
REMARK 290       1555   X,Y,Z
REMARK 290       2555   -X,-Y,Z
REMARK 290       3555   -X,Y,-Z
REMARK 290       4555   X,-Y,-Z
REMARK 290       5555   X+1/2,Y+1/2,Z+1/2
REMARK 290       6555   -X+1/2,-Y+1/2,Z+1/2
REMARK 290       7555   -X+1/2,Y+1/2,-Z+1/2
REMARK 290       8555   X+1/2,-Y+1/2,-Z+1/2
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        0.00000
REMARK 290   SMTRY2   2  0.000000 -1.000000  0.000000        0.00000
REMARK 290   SMTRY3   2  0.000000  0.000000  1.000000        0.00000
REMARK 290   SMTRY1   3 -1.000000  0.000000  0.000000        0.00000
REMARK 290   SMTRY2   3  0.000000  1.000000  0.000000        0.00000
REMARK 290   SMTRY3   3  0.000000  0.000000 -1.000000        0.00000
REMARK 290   SMTRY1   4  1.000000  0.000000  0.000000        0.00000
REMARK 290   SMTRY2   4  0.000000 -1.000000  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       46.31150
REMARK 290   SMTRY2   5  0.000000  1.000000  0.000000       63.60750
REMARK 290   SMTRY3   5  0.000000  0.000000  1.000000       67.98050
REMARK 290   SMTRY1   6 -1.000000  0.000000  0.000000       46.31150
REMARK 290   SMTRY2   6  0.000000 -1.000000  0.000000       63.60750
REMARK 290   SMTRY3   6  0.000000  0.000000  1.000000       67.98050
REMARK 290   SMTRY1   7 -1.000000  0.000000  0.000000       46.31150
REMARK 290   SMTRY2   7  0.000000  1.000000  0.000000       63.60750
REMARK 290   SMTRY3   7  0.000000  0.000000 -1.000000       67.98050
REMARK 290   SMTRY1   8  1.000000  0.000000  0.000000       46.31150
REMARK 290   SMTRY2   8  0.000000 -1.000000  0.000000       63.60750
REMARK 290   SMTRY3   8  0.000000  0.000000 -1.000000       67.98050
REMARK 290
REMARK 290 REMARK: NULL
REMARK 300
REMARK 300 BIOMOLECULE: 1, 2
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 AUTHOR DETERMINED BIOLOGICAL UNIT: MONOMERIC
REMARK 350 SOFTWARE DETERMINED QUATERNARY STRUCTURE: MONOMERIC
REMARK 350 SOFTWARE USED: PISA
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
REMARK 350 BIOMOLECULE: 2
REMARK 350 AUTHOR DETERMINED BIOLOGICAL UNIT: MONOMERIC
REMARK 350 SOFTWARE DETERMINED QUATERNARY STRUCTURE: MONOMERIC
REMARK 350 SOFTWARE USED: PISA
REMARK 350 APPLY THE FOLLOWING TO CHAINS: 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     MET A   -16
REMARK 465     HIS A   -15
REMARK 465     HIS A   -14
REMARK 465     HIS A   -13
REMARK 465     HIS A   -12
REMARK 465     HIS A   -11
REMARK 465     HIS A   -10
REMARK 465     GLY A    -9
REMARK 465     SER A    -8
REMARK 465     GLU A    -7
REMARK 465     ASN A    -6
REMARK 465     LEU A    -5
REMARK 465     TYR A    -4
REMARK 465     PHE A    -3
REMARK 465     GLN A    -2
REMARK 465     GLY A    -1
REMARK 465     SER A     0
REMARK 465     MET A     1
REMARK 465     PRO A     2
REMARK 465     GLU A     3
REMARK 465     GLU A     4
REMARK 465     SER A     5
REMARK 465     SER A     6
REMARK 465     ALA A   295
REMARK 465     THR A   296
REMARK 465     ALA A   297
REMARK 465     GLY A   298
REMARK 465     THR A   299
REMARK 465     ALA A   300
REMARK 465     SER A   301
REMARK 465     PRO A   302
REMARK 465     PRO A   303
REMARK 465     MET B   -16
REMARK 465     HIS B   -15
REMARK 465     HIS B   -14
REMARK 465     HIS B   -13
REMARK 465     HIS B   -12
REMARK 465     HIS B   -11
REMARK 465     HIS B   -10
REMARK 465     GLY B    -9
REMARK 465     SER B    -8
REMARK 465     GLU B    -7
REMARK 465     ASN B    -6
REMARK 465     LEU B    -5
REMARK 465     TYR B    -4
REMARK 465     PHE B    -3
REMARK 465     GLN B    -2
REMARK 465     GLY B    -1
REMARK 465     SER B     0
REMARK 465     MET B     1
REMARK 465     PRO B     2
REMARK 465     GLU B     3
REMARK 465     GLU B     4
REMARK 465     ALA B   295
REMARK 465     THR B   296
REMARK 465     ALA B   297
REMARK 465     GLY B   298
REMARK 465     THR B   299
REMARK 465     ALA B   300
REMARK 465     SER B   301
REMARK 465     PRO B   302
REMARK 465     PRO B   303
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 109    CE   NZ
REMARK 470     GLU A 154    CG   CD   OE1  OE2
REMARK 470     LYS A 160    CG   CD   CE   NZ
REMARK 470     GLU B 154    CG   CD   OE1  OE2
REMARK 470     LYS B 160    CG   CD   CE   NZ
REMARK 470     LYS B 188    CD   CE   NZ
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    PRO A  11       -8.20    -57.12
REMARK 500    SER A  13       26.06     81.50
REMARK 500    GLU A  53     -159.70   -116.00
REMARK 500    VAL A  78      129.71    -39.83
REMARK 500    SER A 122     -123.54     62.04
REMARK 500    SER A 146       62.05     35.84
REMARK 500    ALA A 203      154.50    -46.60
REMARK 500    TYR A 268     -149.02    -89.33
REMARK 500    GLU B  53     -159.54    -98.73
REMARK 500    SER B 122     -122.15     54.93
REMARK 500    VAL B 170      -74.06    -96.97
REMARK 500    SER B 256      130.21    -38.97
REMARK 500    TYR B 268     -155.38    -83.73
REMARK 500
REMARK 500 REMARK: NULL
REMARK 800
REMARK 800 SITE
REMARK 800 SITE_IDENTIFIER: AC1
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: binding site for residue XOV A 401
REMARK 800
REMARK 800 SITE_IDENTIFIER: AC2
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: binding site for residue XOV B 401
DBREF1 7L4W A    0   303  UNP                  A0A0C4DFN3_HUMAN
DBREF2 7L4W A     A0A0C4DFN3                         10         313
DBREF1 7L4W B    0   303  UNP                  A0A0C4DFN3_HUMAN
DBREF2 7L4W B     A0A0C4DFN3                         10         313
SEQADV 7L4W MET A  -16  UNP  A0A0C4DFN           INITIATING METHIONINE
SEQADV 7L4W HIS A  -15  UNP  A0A0C4DFN           EXPRESSION TAG
SEQADV 7L4W HIS A  -14  UNP  A0A0C4DFN           EXPRESSION TAG
SEQADV 7L4W HIS A  -13  UNP  A0A0C4DFN           EXPRESSION TAG
SEQADV 7L4W HIS A  -12  UNP  A0A0C4DFN           EXPRESSION TAG
SEQADV 7L4W HIS A  -11  UNP  A0A0C4DFN           EXPRESSION TAG
SEQADV 7L4W HIS A  -10  UNP  A0A0C4DFN           EXPRESSION TAG
SEQADV 7L4W GLY A   -9  UNP  A0A0C4DFN           EXPRESSION TAG
SEQADV 7L4W SER A   -8  UNP  A0A0C4DFN           EXPRESSION TAG
SEQADV 7L4W GLU A   -7  UNP  A0A0C4DFN           EXPRESSION TAG
SEQADV 7L4W ASN A   -6  UNP  A0A0C4DFN           EXPRESSION TAG
SEQADV 7L4W LEU A   -5  UNP  A0A0C4DFN           EXPRESSION TAG
SEQADV 7L4W TYR A   -4  UNP  A0A0C4DFN           EXPRESSION TAG
SEQADV 7L4W PHE A   -3  UNP  A0A0C4DFN           EXPRESSION TAG
SEQADV 7L4W GLN A   -2  UNP  A0A0C4DFN           EXPRESSION TAG
SEQADV 7L4W GLY A   -1  UNP  A0A0C4DFN           EXPRESSION TAG
SEQADV 7L4W ALA A   36  UNP  A0A0C4DFN LYS    46 CONFLICT
SEQADV 7L4W SER A  169  UNP  A0A0C4DFN LEU   179 CONFLICT
SEQADV 7L4W SER A  176  UNP  A0A0C4DFN LEU   186 CONFLICT
SEQADV 7L4W MET B  -16  UNP  A0A0C4DFN           INITIATING METHIONINE
SEQADV 7L4W HIS B  -15  UNP  A0A0C4DFN           EXPRESSION TAG
SEQADV 7L4W HIS B  -14  UNP  A0A0C4DFN           EXPRESSION TAG
SEQADV 7L4W HIS B  -13  UNP  A0A0C4DFN           EXPRESSION TAG
SEQADV 7L4W HIS B  -12  UNP  A0A0C4DFN           EXPRESSION TAG
SEQADV 7L4W HIS B  -11  UNP  A0A0C4DFN           EXPRESSION TAG
SEQADV 7L4W HIS B  -10  UNP  A0A0C4DFN           EXPRESSION TAG
SEQADV 7L4W GLY B   -9  UNP  A0A0C4DFN           EXPRESSION TAG
SEQADV 7L4W SER B   -8  UNP  A0A0C4DFN           EXPRESSION TAG
SEQADV 7L4W GLU B   -7  UNP  A0A0C4DFN           EXPRESSION TAG
SEQADV 7L4W ASN B   -6  UNP  A0A0C4DFN           EXPRESSION TAG
SEQADV 7L4W LEU B   -5  UNP  A0A0C4DFN           EXPRESSION TAG
SEQADV 7L4W TYR B   -4  UNP  A0A0C4DFN           EXPRESSION TAG
SEQADV 7L4W PHE B   -3  UNP  A0A0C4DFN           EXPRESSION TAG
SEQADV 7L4W GLN B   -2  UNP  A0A0C4DFN           EXPRESSION TAG
SEQADV 7L4W GLY B   -1  UNP  A0A0C4DFN           EXPRESSION TAG
SEQADV 7L4W ALA B   36  UNP  A0A0C4DFN LYS    46 CONFLICT
SEQADV 7L4W SER B  169  UNP  A0A0C4DFN LEU   179 CONFLICT
SEQADV 7L4W SER B  176  UNP  A0A0C4DFN LEU   186 CONFLICT
SEQRES   1 A  320  MET HIS HIS HIS HIS HIS HIS GLY SER GLU ASN LEU TYR
SEQRES   2 A  320  PHE GLN GLY SER MET PRO GLU GLU SER SER PRO ARG ARG
SEQRES   3 A  320  THR PRO GLN SER ILE PRO TYR GLN ASP LEU PRO HIS LEU
SEQRES   4 A  320  VAL ASN ALA ASP GLY GLN TYR LEU PHE CYS ARG TYR TRP
SEQRES   5 A  320  ALA PRO THR GLY THR PRO LYS ALA LEU ILE PHE VAL SER
SEQRES   6 A  320  HIS GLY ALA GLY GLU HIS SER GLY ARG TYR GLU GLU LEU
SEQRES   7 A  320  ALA ARG MET LEU MET GLY LEU ASP LEU LEU VAL PHE ALA
SEQRES   8 A  320  HIS ASP HIS VAL GLY HIS GLY GLN SER GLU GLY GLU ARG
SEQRES   9 A  320  MET VAL VAL SER ASP PHE HIS VAL PHE VAL ARG ASP VAL
SEQRES  10 A  320  LEU GLN HIS VAL ASP SER MET GLN LYS ASP TYR PRO GLY
SEQRES  11 A  320  LEU PRO VAL PHE LEU LEU GLY HIS SER MET GLY GLY ALA
SEQRES  12 A  320  ILE ALA ILE LEU THR ALA ALA GLU ARG PRO GLY HIS PHE
SEQRES  13 A  320  ALA GLY MET VAL LEU ILE SER PRO LEU VAL LEU ALA ASN
SEQRES  14 A  320  PRO GLU SER ALA THR THR PHE LYS VAL LEU ALA ALA LYS
SEQRES  15 A  320  VAL LEU ASN SER VAL LEU PRO ASN LEU SER SER GLY PRO
SEQRES  16 A  320  ILE ASP SER SER VAL LEU SER ARG ASN LYS THR GLU VAL
SEQRES  17 A  320  ASP ILE TYR ASN SER ASP PRO LEU ILE CYS ARG ALA GLY
SEQRES  18 A  320  LEU LYS VAL CYS PHE GLY ILE GLN LEU LEU ASN ALA VAL
SEQRES  19 A  320  SER ARG VAL GLU ARG ALA LEU PRO LYS LEU THR VAL PRO
SEQRES  20 A  320  PHE LEU LEU LEU GLN GLY SER ALA ASP ARG LEU CYS ASP
SEQRES  21 A  320  SER LYS GLY ALA TYR LEU LEU MET GLU LEU ALA LYS SER
SEQRES  22 A  320  GLN ASP LYS THR LEU LYS ILE TYR GLU GLY ALA TYR HIS
SEQRES  23 A  320  VAL LEU HIS LYS GLU LEU PRO GLU VAL THR ASN SER VAL
SEQRES  24 A  320  PHE HIS GLU ILE ASN MET TRP VAL SER GLN ARG THR ALA
SEQRES  25 A  320  THR ALA GLY THR ALA SER PRO PRO
SEQRES   1 B  320  MET HIS HIS HIS HIS HIS HIS GLY SER GLU ASN LEU TYR
SEQRES   2 B  320  PHE GLN GLY SER MET PRO GLU GLU SER SER PRO ARG ARG
SEQRES   3 B  320  THR PRO GLN SER ILE PRO TYR GLN ASP LEU PRO HIS LEU
SEQRES   4 B  320  VAL ASN ALA ASP GLY GLN TYR LEU PHE CYS ARG TYR TRP
SEQRES   5 B  320  ALA PRO THR GLY THR PRO LYS ALA LEU ILE PHE VAL SER
SEQRES   6 B  320  HIS GLY ALA GLY GLU HIS SER GLY ARG TYR GLU GLU LEU
SEQRES   7 B  320  ALA ARG MET LEU MET GLY LEU ASP LEU LEU VAL PHE ALA
SEQRES   8 B  320  HIS ASP HIS VAL GLY HIS GLY GLN SER GLU GLY GLU ARG
SEQRES   9 B  320  MET VAL VAL SER ASP PHE HIS VAL PHE VAL ARG ASP VAL
SEQRES  10 B  320  LEU GLN HIS VAL ASP SER MET GLN LYS ASP TYR PRO GLY
SEQRES  11 B  320  LEU PRO VAL PHE LEU LEU GLY HIS SER MET GLY GLY ALA
SEQRES  12 B  320  ILE ALA ILE LEU THR ALA ALA GLU ARG PRO GLY HIS PHE
SEQRES  13 B  320  ALA GLY MET VAL LEU ILE SER PRO LEU VAL LEU ALA ASN
SEQRES  14 B  320  PRO GLU SER ALA THR THR PHE LYS VAL LEU ALA ALA LYS
SEQRES  15 B  320  VAL LEU ASN SER VAL LEU PRO ASN LEU SER SER GLY PRO
SEQRES  16 B  320  ILE ASP SER SER VAL LEU SER ARG ASN LYS THR GLU VAL
SEQRES  17 B  320  ASP ILE TYR ASN SER ASP PRO LEU ILE CYS ARG ALA GLY
SEQRES  18 B  320  LEU LYS VAL CYS PHE GLY ILE GLN LEU LEU ASN ALA VAL
SEQRES  19 B  320  SER ARG VAL GLU ARG ALA LEU PRO LYS LEU THR VAL PRO
SEQRES  20 B  320  PHE LEU LEU LEU GLN GLY SER ALA ASP ARG LEU CYS ASP
SEQRES  21 B  320  SER LYS GLY ALA TYR LEU LEU MET GLU LEU ALA LYS SER
SEQRES  22 B  320  GLN ASP LYS THR LEU LYS ILE TYR GLU GLY ALA TYR HIS
SEQRES  23 B  320  VAL LEU HIS LYS GLU LEU PRO GLU VAL THR ASN SER VAL
SEQRES  24 B  320  PHE HIS GLU ILE ASN MET TRP VAL SER GLN ARG THR ALA
SEQRES  25 B  320  THR ALA GLY THR ALA SER PRO PRO
HET    XOV  A 401      27
HET    XOV  B 401      27
HETNAM     XOV (2S,4R)-2-{4-[(2-CHLORO-4-FLUOROPHENOXY)
HETNAM   2 XOV  METHYL]PIPERIDINE-1-CARBONYL}-7-OXA-5-
HETNAM   3 XOV  AZASPIRO[3.4]OCTAN-6-ONE
FORMUL   3  XOV    2(C19 H22 CL F N2 O4)
FORMUL   5  HOH   *131(H2 O)
HELIX    1 AA1 PRO A   15  LEU A   19  5                                   5
HELIX    2 AA2 HIS A   54  ARG A   57  5                                   4
HELIX    3 AA3 TYR A   58  GLY A   67  1                                  10
HELIX    4 AA4 PHE A   93  TYR A  111  1                                  19
HELIX    5 AA5 MET A  123  ARG A  135  1                                  13
HELIX    6 AA6 ASN A  152  ALA A  156  5                                   5
HELIX    7 AA7 THR A  157  SER A  169  1                                  13
HELIX    8 AA8 ASP A  180  SER A  185  5                                   6
HELIX    9 AA9 ASN A  187  ASN A  195  1                                   9
HELIX   10 AB1 LYS A  206  LEU A  224  1                                  19
HELIX   11 AB2 PRO A  225  LEU A  227  5                                   3
HELIX   12 AB3 ASP A  243  ALA A  254  1                                  12
HELIX   13 AB4 VAL A  270  GLU A  274  5                                   5
HELIX   14 AB5 LEU A  275  ARG A  293  1                                  19
HELIX   15 AB6 PRO B   15  LEU B   19  5                                   5
HELIX   16 AB7 HIS B   54  ARG B   57  5                                   4
HELIX   17 AB8 TYR B   58  GLY B   67  1                                  10
HELIX   18 AB9 PHE B   93  TYR B  111  1                                  19
HELIX   19 AC1 MET B  123  ARG B  135  1                                  13
HELIX   20 AC2 THR B  157  LEU B  171  1                                  15
HELIX   21 AC3 ASP B  180  LEU B  184  5                                   5
HELIX   22 AC4 ASN B  187  ASP B  197  1                                  11
HELIX   23 AC5 LYS B  206  LEU B  224  1                                  19
HELIX   24 AC6 PRO B  225  LEU B  227  5                                   3
HELIX   25 AC7 SER B  244  ALA B  254  1                                  11
HELIX   26 AC8 VAL B  270  GLU B  274  5                                   5
HELIX   27 AC9 LEU B  275  GLN B  292  1                                  18
SHEET    1 AA1 8 HIS A  21  VAL A  23  0
SHEET    2 AA1 8 TYR A  29  TRP A  35 -1  O  LEU A  30   N  LEU A  22
SHEET    3 AA1 8 LEU A  70  HIS A  75 -1  O  VAL A  72   N  TRP A  35
SHEET    4 AA1 8 ALA A  43  SER A  48  1  N  VAL A  47   O  PHE A  73
SHEET    5 AA1 8 VAL A 116  SER A 122  1  O  LEU A 119   N  SER A  48
SHEET    6 AA1 8 GLY A 141  PRO A 147  1  O  VAL A 143   N  LEU A 118
SHEET    7 AA1 8 PHE A 231  GLY A 236  1  O  LEU A 232   N  LEU A 144
SHEET    8 AA1 8 LYS A 259  TYR A 264  1  O  THR A 260   N  LEU A 233
SHEET    1 AA2 8 HIS B  21  VAL B  23  0
SHEET    2 AA2 8 TYR B  29  TRP B  35 -1  O  LEU B  30   N  LEU B  22
SHEET    3 AA2 8 LEU B  70  HIS B  75 -1  O  VAL B  72   N  TRP B  35
SHEET    4 AA2 8 ALA B  43  SER B  48  1  N  ALA B  43   O  LEU B  71
SHEET    5 AA2 8 VAL B 116  SER B 122  1  O  PHE B 117   N  LEU B  44
SHEET    6 AA2 8 GLY B 141  PRO B 147  1  O  ILE B 145   N  GLY B 120
SHEET    7 AA2 8 PHE B 231  GLY B 236  1  O  LEU B 234   N  SER B 146
SHEET    8 AA2 8 LYS B 259  TYR B 264  1  O  THR B 260   N  LEU B 233
SITE     1 AC1 13 GLY A  50  ALA A  51  GLU A  53  ARG A  57
SITE     2 AC1 13 HIS A 121  SER A 122  MET A 123  TYR A 194
SITE     3 AC1 13 LEU A 205  GLY A 210  HIS A 269  VAL A 270
SITE     4 AC1 13 HOH A 519
SITE     1 AC2 14 GLY B  50  ALA B  51  GLU B  53  ARG B  57
SITE     2 AC2 14 HIS B 121  SER B 122  MET B 123  LEU B 148
SITE     3 AC2 14 LEU B 205  GLY B 210  LEU B 213  HIS B 269
SITE     4 AC2 14 VAL B 270  HOH B 513
CRYST1   92.623  127.215  135.961  90.00  90.00  90.00 I 2 2 2      16
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      0.010796  0.000000  0.000000        0.00000
SCALE2      0.000000  0.007861  0.000000        0.00000
SCALE3      0.000000  0.000000  0.007355        0.00000
TER    2224      THR A 294
TER    4459      THR B 294
MASTER      419    0    2   27   16    0    8    6 4642    2   54   50
END