HEADER APOPTOSIS/INHIBITOR 07-NOV-12 4HW2
TITLE DISCOVERY OF POTENT MCL-1 INHIBITORS USING FRAGMENT-BASED METHODS AND
TITLE 2 STRUCTURE-BASED DESIGN
COMPND MOL_ID: 1;
COMPND 2 MOLECULE: INDUCED MYELOID LEUKEMIA CELL DIFFERENTIATION PROTEIN MCL-
COMPND 3 1;
COMPND 4 CHAIN: A, B, C, D, E, F;
COMPND 5 SYNONYM: BCL-2-LIKE PROTEIN 3, BCL2-L-3, BCL-2-RELATED PROTEIN
COMPND 6 EAT/MCL1, MCL1/EAT;
COMPND 7 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: MCL1, BCL2L3;
SOURCE 6 EXPRESSION_SYSTEM: ESCHERICHIA COLI;
SOURCE 7 EXPRESSION_SYSTEM_TAXID: 562;
SOURCE 8 EXPRESSION_SYSTEM_STRAIN: BL21-CODONPLUS (DE3)-RIL;
SOURCE 9 EXPRESSION_SYSTEM_VECTOR_TYPE: PLASMID;
SOURCE 10 EXPRESSION_SYSTEM_PLASMID: PDEST-HISMBP
KEYWDS REGULATION OF APOPTOSIS, MAINTENANCE OF VIABILITY, APOPTOSIS,
KEYWDS 2 APOPTOSIS-INHIBITOR COMPLEX
EXPDTA X-RAY DIFFRACTION
AUTHOR B.ZHAO
REVDAT 2 06-MAR-13 4HW2 1 JRNL
REVDAT 1 09-JAN-13 4HW2 0
JRNL AUTH A.FRIBERG,D.VIGIL,B.ZHAO,R.N.DANIELS,J.P.BURKE,
JRNL AUTH 2 P.M.GARCIA-BARRANTES,D.CAMPER,B.A.CHAUDER,T.LEE,
JRNL AUTH 3 E.T.OLEJNICZAK,S.W.FESIK
JRNL TITL DISCOVERY OF POTENT MYELOID CELL LEUKEMIA 1 (MCL-1)
JRNL TITL 2 INHIBITORS USING FRAGMENT-BASED METHODS AND STRUCTURE-BASED
JRNL TITL 3 DESIGN.
JRNL REF J.MED.CHEM. V. 56 15 2013
JRNL REFN ISSN 0022-2623
JRNL PMID 23244564
JRNL DOI 10.1021/JM301448P
REMARK 2
REMARK 2 RESOLUTION. 2.80 ANGSTROMS.
REMARK 3
REMARK 3 REFINEMENT.
REMARK 3 PROGRAM : CNS 1.3
REMARK 3 AUTHORS : BRUNGER,ADAMS,CLORE,DELANO,GROS,GROSSE-
REMARK 3 : KUNSTLEVE,JIANG,KUSZEWSKI,NILGES,PANNU,
REMARK 3 : READ,RICE,SIMONSON,WARREN
REMARK 3
REMARK 3 REFINEMENT TARGET : ENGH & HUBER
REMARK 3
REMARK 3 DATA USED IN REFINEMENT.
REMARK 3 RESOLUTION RANGE HIGH (ANGSTROMS) : 2.80
REMARK 3 RESOLUTION RANGE LOW (ANGSTROMS) : 30.00
REMARK 3 DATA CUTOFF (SIGMA(F)) : 0.000
REMARK 3 DATA CUTOFF HIGH (ABS(F)) : NULL
REMARK 3 DATA CUTOFF LOW (ABS(F)) : NULL
REMARK 3 COMPLETENESS (WORKING+TEST) (%) : NULL
REMARK 3 NUMBER OF REFLECTIONS : 25097
REMARK 3
REMARK 3 FIT TO DATA USED IN REFINEMENT.
REMARK 3 CROSS-VALIDATION METHOD : NULL
REMARK 3 FREE R VALUE TEST SET SELECTION : RANDOM
REMARK 3 R VALUE (WORKING SET) : 0.217
REMARK 3 FREE R VALUE : 0.245
REMARK 3 FREE R VALUE TEST SET SIZE (%) : NULL
REMARK 3 FREE R VALUE TEST SET COUNT : 2490
REMARK 3 ESTIMATED ERROR OF FREE R VALUE : NULL
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) : 2.80
REMARK 3 BIN RESOLUTION RANGE LOW (A) : 2.90
REMARK 3 BIN COMPLETENESS (WORKING+TEST) (%) : 93.30
REMARK 3 REFLECTIONS IN BIN (WORKING SET) : NULL
REMARK 3 BIN R VALUE (WORKING SET) : 0.3151
REMARK 3 BIN FREE R VALUE : 0.3633
REMARK 3 BIN FREE R VALUE TEST SET SIZE (%) : NULL
REMARK 3 BIN FREE R VALUE TEST SET COUNT : 234
REMARK 3 ESTIMATED ERROR OF BIN FREE R VALUE : NULL
REMARK 3
REMARK 3 NUMBER OF NON-HYDROGEN ATOMS USED IN REFINEMENT.
REMARK 3 PROTEIN ATOMS : 7186
REMARK 3 NUCLEIC ACID ATOMS : 0
REMARK 3 HETEROGEN ATOMS : 190
REMARK 3 SOLVENT ATOMS : 0
REMARK 3
REMARK 3 B VALUES.
REMARK 3 FROM WILSON PLOT (A**2) : 4.10
REMARK 3 MEAN B VALUE (OVERALL, A**2) : 51.30
REMARK 3 OVERALL ANISOTROPIC B VALUE.
REMARK 3 B11 (A**2) : -0.23000
REMARK 3 B22 (A**2) : -0.02000
REMARK 3 B33 (A**2) : 0.25000
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 COORDINATE ERROR.
REMARK 3 ESD FROM LUZZATI PLOT (A) : 0.35
REMARK 3 ESD FROM SIGMAA (A) : 0.45
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) : 0.40
REMARK 3 ESD FROM C-V SIGMAA (A) : 0.54
REMARK 3
REMARK 3 RMS DEVIATIONS FROM IDEAL VALUES.
REMARK 3 BOND LENGTHS (A) : 0.024
REMARK 3 BOND ANGLES (DEGREES) : NULL
REMARK 3 DIHEDRAL ANGLES (DEGREES) : NULL
REMARK 3 IMPROPER ANGLES (DEGREES) : NULL
REMARK 3
REMARK 3 ISOTROPIC THERMAL MODEL : ANISOTROPIC
REMARK 3
REMARK 3 ISOTROPIC THERMAL FACTOR RESTRAINTS. RMS SIGMA
REMARK 3 MAIN-CHAIN BOND (A**2) : NULL ; NULL
REMARK 3 MAIN-CHAIN ANGLE (A**2) : NULL ; NULL
REMARK 3 SIDE-CHAIN BOND (A**2) : NULL ; NULL
REMARK 3 SIDE-CHAIN ANGLE (A**2) : NULL ; NULL
REMARK 3
REMARK 3 BULK SOLVENT MODELING.
REMARK 3 METHOD USED : NULL
REMARK 3 KSOL : NULL
REMARK 3 BSOL : NULL
REMARK 3
REMARK 3 NCS MODEL : NULL
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 : NULL
REMARK 3 TOPOLOGY FILE 1 : NULL
REMARK 3
REMARK 3 OTHER REFINEMENT REMARKS: NULL
REMARK 4
REMARK 4 4HW2 COMPLIES WITH FORMAT V. 3.30, 13-JUL-11
REMARK 100
REMARK 100 THIS ENTRY HAS BEEN PROCESSED BY RCSB ON 08-NOV-12.
REMARK 100 THE RCSB ID CODE IS RCSB075991.
REMARK 200
REMARK 200 EXPERIMENTAL DETAILS
REMARK 200 EXPERIMENT TYPE : X-RAY DIFFRACTION
REMARK 200 DATE OF DATA COLLECTION : 11-JUL-12
REMARK 200 TEMPERATURE (KELVIN) : 100
REMARK 200 PH : 6.5
REMARK 200 NUMBER OF CRYSTALS USED : 1
REMARK 200
REMARK 200 SYNCHROTRON (Y/N) : Y
REMARK 200 RADIATION SOURCE : APS
REMARK 200 BEAMLINE : 21-ID-D
REMARK 200 X-RAY GENERATOR MODEL : NULL
REMARK 200 MONOCHROMATIC OR LAUE (M/L) : M
REMARK 200 WAVELENGTH OR RANGE (A) : 1.07816
REMARK 200 MONOCHROMATOR : SAGITALLY FOCUSED SI(111)
REMARK 200 OPTICS : NULL
REMARK 200
REMARK 200 DETECTOR TYPE : CCD
REMARK 200 DETECTOR MANUFACTURER : MAR SCANNER 300 MM PLATE
REMARK 200 INTENSITY-INTEGRATION SOFTWARE : HKL-2000
REMARK 200 DATA SCALING SOFTWARE : HKL-2000
REMARK 200
REMARK 200 NUMBER OF UNIQUE REFLECTIONS : 25097
REMARK 200 RESOLUTION RANGE HIGH (A) : 2.800
REMARK 200 RESOLUTION RANGE LOW (A) : 50.000
REMARK 200 REJECTION CRITERIA (SIGMA(I)) : 2.000
REMARK 200
REMARK 200 OVERALL.
REMARK 200 COMPLETENESS FOR RANGE (%) : 97.7
REMARK 200 DATA REDUNDANCY : NULL
REMARK 200 R MERGE (I) : 0.04700
REMARK 200 R SYM (I) : 0.05700
REMARK 200 <I/SIGMA(I)> FOR THE DATA SET : 21.7000
REMARK 200
REMARK 200 IN THE HIGHEST RESOLUTION SHELL.
REMARK 200 HIGHEST RESOLUTION SHELL, RANGE HIGH (A) : 2.80
REMARK 200 HIGHEST RESOLUTION SHELL, RANGE LOW (A) : 2.85
REMARK 200 COMPLETENESS FOR SHELL (%) : 95.0
REMARK 200 DATA REDUNDANCY IN SHELL : 3.40
REMARK 200 R MERGE FOR SHELL (I) : 0.41100
REMARK 200 R SYM FOR SHELL (I) : 0.29700
REMARK 200 <I/SIGMA(I)> FOR SHELL : 3.000
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: NULL
REMARK 200
REMARK 200 REMARK: NULL
REMARK 280
REMARK 280 CRYSTAL
REMARK 280 SOLVENT CONTENT, VS (%): 49.21
REMARK 280 MATTHEWS COEFFICIENT, VM (ANGSTROMS**3/DA): 2.42
REMARK 280
REMARK 280 CRYSTALLIZATION CONDITIONS: 30% PEG3350, 0.2M MGCL2, PH 6.5, VAPOR
REMARK 280 DIFFUSION, HANGING DROP, TEMPERATURE 298K
REMARK 290
REMARK 290 CRYSTALLOGRAPHIC SYMMETRY
REMARK 290 SYMMETRY OPERATORS FOR SPACE GROUP: P 21 21 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+1/2,Y+1/2,-Z
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 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 60.99850
REMARK 290 SMTRY2 3 0.000000 1.000000 0.000000 67.16350
REMARK 290 SMTRY3 3 0.000000 0.000000 -1.000000 0.00000
REMARK 290 SMTRY1 4 1.000000 0.000000 0.000000 60.99850
REMARK 290 SMTRY2 4 0.000000 -1.000000 0.000000 67.16350
REMARK 290 SMTRY3 4 0.000000 0.000000 -1.000000 0.00000
REMARK 290
REMARK 290 REMARK: NULL
REMARK 300
REMARK 300 BIOMOLECULE: 1, 2, 3, 4, 5, 6
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 350
REMARK 350 BIOMOLECULE: 3
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: C
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: 4
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: D
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: 5
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: E
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: 6
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: F
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 GLY A 200
REMARK 465 ARG A 201
REMARK 465 GLU A 322
REMARK 465 ASP A 323
REMARK 465 GLU B 322
REMARK 465 ASP B 323
REMARK 465 VAL C 321
REMARK 465 GLU C 322
REMARK 465 ASP C 323
REMARK 465 GLU D 322
REMARK 465 ASP D 323
REMARK 465 GLU E 322
REMARK 465 ASP E 323
REMARK 465 VAL F 321
REMARK 465 GLU F 322
REMARK 465 ASP F 323
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 194 CG CD CE NZ
REMARK 470 LYS A 197 CG CD CE NZ
REMARK 470 MET A 199 CG SD CE
REMARK 470 LYS C 194 CG CD CE NZ
REMARK 470 ASP C 195 CG OD1 OD2
REMARK 470 LYS C 197 CG CD CE NZ
REMARK 470 ARG C 201 CG CD NE CZ NH1 NH2
REMARK 470 ASP C 236 CG OD1 OD2
REMARK 470 ARG D 201 CG CD NE CZ NH1 NH2
REMARK 470 ASP D 236 CG OD1 OD2
REMARK 470 ASP E 236 CG OD1 OD2
REMARK 470 LYS F 194 CG CD CE NZ
REMARK 470 LYS F 197 CG CD CE NZ
REMARK 470 ARG F 201 CG CD NE CZ NH1 NH2
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 PROTEIN: ENGH AND HUBER, 1999
REMARK 500 EXPECTED VALUES NUCLEIC ACID: CLOWNEY ET AL 1996
REMARK 500
REMARK 500 M RES CSSEQI ATM1 ATM2 ATM3
REMARK 500 GLY E 200 N - CA - C ANGL. DEV. = 20.7 DEGREES
REMARK 500 ARG F 215 NE - CZ - NH1 ANGL. DEV. = 5.6 DEGREES
REMARK 500 ARG F 215 NE - CZ - NH2 ANGL. DEV. = -8.3 DEGREES
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 ASP A 172 -128.21 55.68
REMARK 500 THR A 191 155.10 92.85
REMARK 500 ALA A 193 150.44 83.47
REMARK 500 ASP B 172 -134.19 51.32
REMARK 500 ALA B 193 174.97 77.47
REMARK 500 ASP C 172 -123.99 55.67
REMARK 500 THR C 191 169.88 69.64
REMARK 500 LYS C 197 11.49 118.04
REMARK 500 ARG C 201 -73.42 -50.13
REMARK 500 ASP D 172 -109.62 34.15
REMARK 500 THR D 191 -51.55 60.38
REMARK 500 ALA D 193 -158.00 -51.87
REMARK 500 MET D 199 -61.35 63.65
REMARK 500 SER D 202 39.25 71.74
REMARK 500 PHE D 318 -25.48 -172.40
REMARK 500 ASP E 172 -118.19 54.38
REMARK 500 THR E 191 -2.63 68.57
REMARK 500 ASP F 172 -125.84 46.24
REMARK 500 THR F 191 -98.72 -125.58
REMARK 500 THR F 196 -72.10 -82.86
REMARK 500 LYS F 197 151.64 -16.33
REMARK 500 SER F 202 29.82 158.80
REMARK 500 GLU F 240 -23.01 -23.97
REMARK 500 VAL F 258 -102.37 -106.56
REMARK 500 THR F 259 144.53 133.45
REMARK 500
REMARK 500 REMARK: NULL
REMARK 500
REMARK 500 GEOMETRY AND STEREOCHEMISTRY
REMARK 500 SUBTOPIC: PLANAR GROUPS
REMARK 500
REMARK 500 PLANAR GROUPS IN THE FOLLOWING RESIDUES HAVE A TOTAL
REMARK 500 RMS DISTANCE OF ALL ATOMS FROM THE BEST-FIT PLANE
REMARK 500 BY MORE THAN AN EXPECTED VALUE OF 6*RMSD, WITH AN
REMARK 500 RMSD 0.02 ANGSTROMS, OR AT LEAST ONE ATOM HAS
REMARK 500 AN RMSD GREATER THAN THIS VALUE
REMARK 500 (M=MODEL NUMBER; RES=RESIDUE NAME; C=CHAIN IDENTIFIER;
REMARK 500 SSEQ=SEQUENCE NUMBER; I=INSERTION CODE).
REMARK 500
REMARK 500 M RES CSSEQI RMS TYPE
REMARK 500 ARG B 248 0.29 SIDE CHAIN
REMARK 500 ARG C 215 0.29 SIDE CHAIN
REMARK 500 ARG F 176 0.30 SIDE CHAIN
REMARK 500 ARG F 215 0.20 SIDE CHAIN
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 19H A 401
REMARK 800
REMARK 800 SITE_IDENTIFIER: AC2
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: BINDING SITE FOR RESIDUE PGE A 402
REMARK 800
REMARK 800 SITE_IDENTIFIER: AC3
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: BINDING SITE FOR RESIDUE 19H B 401
REMARK 800
REMARK 800 SITE_IDENTIFIER: AC4
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: BINDING SITE FOR RESIDUE PGE B 402
REMARK 800
REMARK 800 SITE_IDENTIFIER: AC5
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: BINDING SITE FOR RESIDUE PGE B 403
REMARK 800
REMARK 800 SITE_IDENTIFIER: AC6
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: BINDING SITE FOR RESIDUE EDO B 404
REMARK 800
REMARK 800 SITE_IDENTIFIER: AC7
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: BINDING SITE FOR RESIDUE 19H C 400
REMARK 800
REMARK 800 SITE_IDENTIFIER: AC8
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: BINDING SITE FOR RESIDUE 19H D 400
REMARK 800
REMARK 800 SITE_IDENTIFIER: AC9
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: BINDING SITE FOR RESIDUE 19H E 400
REMARK 800
REMARK 800 SITE_IDENTIFIER: BC1
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: BINDING SITE FOR RESIDUE 19H F 400
REMARK 900
REMARK 900 RELATED ENTRIES
REMARK 900 RELATED ID: 4HW3 RELATED DB: PDB
REMARK 900 RELATED ID: 4HW4 RELATED DB: PDB
DBREF 4HW2 A 172 323 UNP Q07820 MCL1_HUMAN 172 323
DBREF 4HW2 B 172 323 UNP Q07820 MCL1_HUMAN 172 323
DBREF 4HW2 C 172 323 UNP Q07820 MCL1_HUMAN 172 323
DBREF 4HW2 D 172 323 UNP Q07820 MCL1_HUMAN 172 323
DBREF 4HW2 E 172 323 UNP Q07820 MCL1_HUMAN 172 323
DBREF 4HW2 F 172 323 UNP Q07820 MCL1_HUMAN 172 323
SEQADV 4HW2 GLY A 171 UNP Q07820 EXPRESSION TAG
SEQADV 4HW2 GLY B 171 UNP Q07820 EXPRESSION TAG
SEQADV 4HW2 GLY C 171 UNP Q07820 EXPRESSION TAG
SEQADV 4HW2 GLY D 171 UNP Q07820 EXPRESSION TAG
SEQADV 4HW2 GLY E 171 UNP Q07820 EXPRESSION TAG
SEQADV 4HW2 GLY F 171 UNP Q07820 EXPRESSION TAG
SEQRES 1 A 153 GLY ASP GLU LEU TYR ARG GLN SER LEU GLU ILE ILE SER
SEQRES 2 A 153 ARG TYR LEU ARG GLU GLN ALA THR GLY ALA LYS ASP THR
SEQRES 3 A 153 LYS PRO MET GLY ARG SER GLY ALA THR SER ARG LYS ALA
SEQRES 4 A 153 LEU GLU THR LEU ARG ARG VAL GLY ASP GLY VAL GLN ARG
SEQRES 5 A 153 ASN HIS GLU THR ALA PHE GLN GLY MET LEU ARG LYS LEU
SEQRES 6 A 153 ASP ILE LYS ASN GLU ASP ASP VAL LYS SER LEU SER ARG
SEQRES 7 A 153 VAL MET ILE HIS VAL PHE SER ASP GLY VAL THR ASN TRP
SEQRES 8 A 153 GLY ARG ILE VAL THR LEU ILE SER PHE GLY ALA PHE VAL
SEQRES 9 A 153 ALA LYS HIS LEU LYS THR ILE ASN GLN GLU SER CYS ILE
SEQRES 10 A 153 GLU PRO LEU ALA GLU SER ILE THR ASP VAL LEU VAL ARG
SEQRES 11 A 153 THR LYS ARG ASP TRP LEU VAL LYS GLN ARG GLY TRP ASP
SEQRES 12 A 153 GLY PHE VAL GLU PHE PHE HIS VAL GLU ASP
SEQRES 1 B 153 GLY ASP GLU LEU TYR ARG GLN SER LEU GLU ILE ILE SER
SEQRES 2 B 153 ARG TYR LEU ARG GLU GLN ALA THR GLY ALA LYS ASP THR
SEQRES 3 B 153 LYS PRO MET GLY ARG SER GLY ALA THR SER ARG LYS ALA
SEQRES 4 B 153 LEU GLU THR LEU ARG ARG VAL GLY ASP GLY VAL GLN ARG
SEQRES 5 B 153 ASN HIS GLU THR ALA PHE GLN GLY MET LEU ARG LYS LEU
SEQRES 6 B 153 ASP ILE LYS ASN GLU ASP ASP VAL LYS SER LEU SER ARG
SEQRES 7 B 153 VAL MET ILE HIS VAL PHE SER ASP GLY VAL THR ASN TRP
SEQRES 8 B 153 GLY ARG ILE VAL THR LEU ILE SER PHE GLY ALA PHE VAL
SEQRES 9 B 153 ALA LYS HIS LEU LYS THR ILE ASN GLN GLU SER CYS ILE
SEQRES 10 B 153 GLU PRO LEU ALA GLU SER ILE THR ASP VAL LEU VAL ARG
SEQRES 11 B 153 THR LYS ARG ASP TRP LEU VAL LYS GLN ARG GLY TRP ASP
SEQRES 12 B 153 GLY PHE VAL GLU PHE PHE HIS VAL GLU ASP
SEQRES 1 C 153 GLY ASP GLU LEU TYR ARG GLN SER LEU GLU ILE ILE SER
SEQRES 2 C 153 ARG TYR LEU ARG GLU GLN ALA THR GLY ALA LYS ASP THR
SEQRES 3 C 153 LYS PRO MET GLY ARG SER GLY ALA THR SER ARG LYS ALA
SEQRES 4 C 153 LEU GLU THR LEU ARG ARG VAL GLY ASP GLY VAL GLN ARG
SEQRES 5 C 153 ASN HIS GLU THR ALA PHE GLN GLY MET LEU ARG LYS LEU
SEQRES 6 C 153 ASP ILE LYS ASN GLU ASP ASP VAL LYS SER LEU SER ARG
SEQRES 7 C 153 VAL MET ILE HIS VAL PHE SER ASP GLY VAL THR ASN TRP
SEQRES 8 C 153 GLY ARG ILE VAL THR LEU ILE SER PHE GLY ALA PHE VAL
SEQRES 9 C 153 ALA LYS HIS LEU LYS THR ILE ASN GLN GLU SER CYS ILE
SEQRES 10 C 153 GLU PRO LEU ALA GLU SER ILE THR ASP VAL LEU VAL ARG
SEQRES 11 C 153 THR LYS ARG ASP TRP LEU VAL LYS GLN ARG GLY TRP ASP
SEQRES 12 C 153 GLY PHE VAL GLU PHE PHE HIS VAL GLU ASP
SEQRES 1 D 153 GLY ASP GLU LEU TYR ARG GLN SER LEU GLU ILE ILE SER
SEQRES 2 D 153 ARG TYR LEU ARG GLU GLN ALA THR GLY ALA LYS ASP THR
SEQRES 3 D 153 LYS PRO MET GLY ARG SER GLY ALA THR SER ARG LYS ALA
SEQRES 4 D 153 LEU GLU THR LEU ARG ARG VAL GLY ASP GLY VAL GLN ARG
SEQRES 5 D 153 ASN HIS GLU THR ALA PHE GLN GLY MET LEU ARG LYS LEU
SEQRES 6 D 153 ASP ILE LYS ASN GLU ASP ASP VAL LYS SER LEU SER ARG
SEQRES 7 D 153 VAL MET ILE HIS VAL PHE SER ASP GLY VAL THR ASN TRP
SEQRES 8 D 153 GLY ARG ILE VAL THR LEU ILE SER PHE GLY ALA PHE VAL
SEQRES 9 D 153 ALA LYS HIS LEU LYS THR ILE ASN GLN GLU SER CYS ILE
SEQRES 10 D 153 GLU PRO LEU ALA GLU SER ILE THR ASP VAL LEU VAL ARG
SEQRES 11 D 153 THR LYS ARG ASP TRP LEU VAL LYS GLN ARG GLY TRP ASP
SEQRES 12 D 153 GLY PHE VAL GLU PHE PHE HIS VAL GLU ASP
SEQRES 1 E 153 GLY ASP GLU LEU TYR ARG GLN SER LEU GLU ILE ILE SER
SEQRES 2 E 153 ARG TYR LEU ARG GLU GLN ALA THR GLY ALA LYS ASP THR
SEQRES 3 E 153 LYS PRO MET GLY ARG SER GLY ALA THR SER ARG LYS ALA
SEQRES 4 E 153 LEU GLU THR LEU ARG ARG VAL GLY ASP GLY VAL GLN ARG
SEQRES 5 E 153 ASN HIS GLU THR ALA PHE GLN GLY MET LEU ARG LYS LEU
SEQRES 6 E 153 ASP ILE LYS ASN GLU ASP ASP VAL LYS SER LEU SER ARG
SEQRES 7 E 153 VAL MET ILE HIS VAL PHE SER ASP GLY VAL THR ASN TRP
SEQRES 8 E 153 GLY ARG ILE VAL THR LEU ILE SER PHE GLY ALA PHE VAL
SEQRES 9 E 153 ALA LYS HIS LEU LYS THR ILE ASN GLN GLU SER CYS ILE
SEQRES 10 E 153 GLU PRO LEU ALA GLU SER ILE THR ASP VAL LEU VAL ARG
SEQRES 11 E 153 THR LYS ARG ASP TRP LEU VAL LYS GLN ARG GLY TRP ASP
SEQRES 12 E 153 GLY PHE VAL GLU PHE PHE HIS VAL GLU ASP
SEQRES 1 F 153 GLY ASP GLU LEU TYR ARG GLN SER LEU GLU ILE ILE SER
SEQRES 2 F 153 ARG TYR LEU ARG GLU GLN ALA THR GLY ALA LYS ASP THR
SEQRES 3 F 153 LYS PRO MET GLY ARG SER GLY ALA THR SER ARG LYS ALA
SEQRES 4 F 153 LEU GLU THR LEU ARG ARG VAL GLY ASP GLY VAL GLN ARG
SEQRES 5 F 153 ASN HIS GLU THR ALA PHE GLN GLY MET LEU ARG LYS LEU
SEQRES 6 F 153 ASP ILE LYS ASN GLU ASP ASP VAL LYS SER LEU SER ARG
SEQRES 7 F 153 VAL MET ILE HIS VAL PHE SER ASP GLY VAL THR ASN TRP
SEQRES 8 F 153 GLY ARG ILE VAL THR LEU ILE SER PHE GLY ALA PHE VAL
SEQRES 9 F 153 ALA LYS HIS LEU LYS THR ILE ASN GLN GLU SER CYS ILE
SEQRES 10 F 153 GLU PRO LEU ALA GLU SER ILE THR ASP VAL LEU VAL ARG
SEQRES 11 F 153 THR LYS ARG ASP TRP LEU VAL LYS GLN ARG GLY TRP ASP
SEQRES 12 F 153 GLY PHE VAL GLU PHE PHE HIS VAL GLU ASP
HET 19H A 401 26
HET PGE A 402 10
HET 19H B 401 26
HET PGE B 402 10
HET PGE B 403 10
HET EDO B 404 4
HET 19H C 400 26
HET 19H D 400 26
HET 19H E 400 26
HET 19H F 400 26
HETNAM 19H 6-CHLORO-3-[3-(4-CHLORO-3,5-DIMETHYLPHENOXY)PROPYL]-1H-
HETNAM 2 19H INDOLE-2-CARBOXYLIC ACID
HETNAM PGE TRIETHYLENE GLYCOL
HETNAM EDO 1,2-ETHANEDIOL
HETSYN EDO ETHYLENE GLYCOL
FORMUL 7 19H 6(C20 H19 CL2 N O3)
FORMUL 8 PGE 3(C6 H14 O4)
FORMUL 12 EDO C2 H6 O2
HELIX 1 1 ASP A 172 ALA A 190 1 19
HELIX 2 2 ALA A 204 HIS A 224 1 21
HELIX 3 3 HIS A 224 ASP A 236 1 13
HELIX 4 4 ASN A 239 LYS A 244 1 6
HELIX 5 5 LEU A 246 SER A 255 1 10
HELIX 6 6 ASN A 260 ILE A 281 1 22
HELIX 7 7 GLN A 283 SER A 285 5 3
HELIX 8 8 CYS A 286 GLN A 309 1 24
HELIX 9 9 GLY A 311 PHE A 319 1 9
HELIX 10 10 ASP B 172 ALA B 190 1 19
HELIX 11 11 SER B 202 HIS B 224 1 23
HELIX 12 12 HIS B 224 ASP B 236 1 13
HELIX 13 13 ASN B 239 SER B 245 1 7
HELIX 14 14 LEU B 246 SER B 255 1 10
HELIX 15 15 ASN B 260 ILE B 281 1 22
HELIX 16 16 GLN B 283 SER B 285 5 3
HELIX 17 17 CYS B 286 LYS B 302 1 17
HELIX 18 18 LYS B 302 GLN B 309 1 8
HELIX 19 19 ARG B 310 PHE B 319 1 10
HELIX 20 20 ASP C 172 ALA C 190 1 19
HELIX 21 21 SER C 202 HIS C 224 1 23
HELIX 22 22 HIS C 224 ASP C 236 1 13
HELIX 23 23 ASN C 239 LYS C 244 1 6
HELIX 24 24 SER C 245 SER C 255 1 11
HELIX 25 25 ASN C 260 ILE C 281 1 22
HELIX 26 26 GLN C 283 SER C 285 5 3
HELIX 27 27 CYS C 286 LYS C 302 1 17
HELIX 28 28 LYS C 302 GLN C 309 1 8
HELIX 29 29 ARG C 310 PHE C 319 1 10
HELIX 30 30 ASP D 172 ALA D 190 1 19
HELIX 31 31 SER D 202 HIS D 224 1 23
HELIX 32 32 HIS D 224 ASP D 236 1 13
HELIX 33 33 ASN D 239 SER D 245 1 7
HELIX 34 34 LEU D 246 SER D 255 1 10
HELIX 35 35 ASN D 260 ILE D 281 1 22
HELIX 36 36 GLN D 283 SER D 285 5 3
HELIX 37 37 CYS D 286 LYS D 302 1 17
HELIX 38 38 LYS D 302 GLN D 309 1 8
HELIX 39 39 ARG D 310 GLU D 317 1 8
HELIX 40 40 ASP E 172 ALA E 190 1 19
HELIX 41 41 ALA E 204 HIS E 224 1 21
HELIX 42 42 HIS E 224 ASP E 236 1 13
HELIX 43 43 ASN E 239 LYS E 244 1 6
HELIX 44 44 LEU E 246 SER E 255 1 10
HELIX 45 45 ASN E 260 ILE E 281 1 22
HELIX 46 46 GLN E 283 SER E 285 5 3
HELIX 47 47 CYS E 286 LYS E 302 1 17
HELIX 48 48 LYS E 302 GLN E 309 1 8
HELIX 49 49 ARG E 310 PHE E 319 1 10
HELIX 50 50 ASP F 172 THR F 191 1 20
HELIX 51 51 ALA F 204 HIS F 224 1 21
HELIX 52 52 HIS F 224 ASP F 236 1 13
HELIX 53 53 ASN F 239 SER F 245 1 7
HELIX 54 54 LEU F 246 SER F 255 1 10
HELIX 55 55 ASN F 260 ILE F 281 1 22
HELIX 56 56 GLN F 283 SER F 285 5 3
HELIX 57 57 CYS F 286 LYS F 302 1 17
HELIX 58 58 LYS F 302 GLN F 309 1 8
HELIX 59 59 ARG F 310 HIS F 320 1 11
CISPEP 1 ALA B 193 LYS B 194 0 -20.90
CISPEP 2 ALA D 193 LYS D 194 0 24.72
SITE 1 AC1 11 ALA A 227 PHE A 228 VAL A 249 MET A 250
SITE 2 AC1 11 VAL A 253 PHE A 254 ARG A 263 LEU A 267
SITE 3 AC1 11 PHE A 270 GLY A 271 ILE A 294
SITE 1 AC2 1 HIS A 224
SITE 1 AC3 8 ALA B 227 PHE B 228 MET B 250 VAL B 253
SITE 2 AC3 8 PHE B 254 ARG B 263 LEU B 267 PHE B 270
SITE 1 AC4 2 HIS B 224 THR B 266
SITE 1 AC5 4 ASN B 223 HIS B 224 GLY B 262 PHE B 318
SITE 1 AC6 4 ASN B 223 HIS B 224 THR B 226 ALA B 227
SITE 1 AC7 9 ALA C 227 PHE C 228 MET C 231 VAL C 253
SITE 2 AC7 9 PHE C 254 ARG C 263 LEU C 267 PHE C 270
SITE 3 AC7 9 GLY C 271
SITE 1 AC8 9 PHE D 228 MET D 231 LEU D 246 VAL D 253
SITE 2 AC8 9 PHE D 254 ARG D 263 LEU D 267 PHE D 270
SITE 3 AC8 9 GLY D 271
SITE 1 AC9 9 ALA E 227 MET E 231 LEU E 246 MET E 250
SITE 2 AC9 9 VAL E 253 PHE E 254 ARG E 263 LEU E 267
SITE 3 AC9 9 PHE E 270
SITE 1 BC1 11 LYS E 194 ARG E 207 ALA F 227 PHE F 228
SITE 2 BC1 11 MET F 231 MET F 250 VAL F 253 PHE F 254
SITE 3 BC1 11 ARG F 263 LEU F 267 PHE F 270
CRYST1 121.997 134.327 62.043 90.00 90.00 90.00 P 21 21 2 24
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 0.008197 0.000000 0.000000 0.00000
SCALE2 0.000000 0.007445 0.000000 0.00000
SCALE3 0.000000 0.000000 0.016118 0.00000
(ATOM LINES ARE NOT SHOWN.)
END
