HEADER TRANSFERASE/TRANSFERASE INHIBITOR 02-APR-12 4EHG
TITLE B-RAF KINASE DOMAIN IN COMPLEX WITH AN AMINOPYRIDIMINE-BASED INHIBITOR
COMPND MOL_ID: 1;
COMPND 2 MOLECULE: SERINE/THREONINE-PROTEIN KINASE B-RAF;
COMPND 3 CHAIN: A, B;
COMPND 4 FRAGMENT: KINASE DOMAIN;
COMPND 5 SYNONYM: PROTO-ONCOGENE B-RAF, P94, V-RAF MURINE SARCOMA VIRAL
COMPND 6 ONCOGENE HOMOLOG B1;
COMPND 7 EC: 2.7.11.1;
COMPND 8 ENGINEERED: YES;
COMPND 9 MUTATION: YES
SOURCE MOL_ID: 1;
SOURCE 2 ORGANISM_SCIENTIFIC: HOMO SAPIENS;
SOURCE 3 ORGANISM_COMMON: HUMAN;
SOURCE 4 ORGANISM_TAXID: 9606;
SOURCE 5 GENE: BRAF, BRAF1, RAFB1;
SOURCE 6 EXPRESSION_SYSTEM: TRICHOPLUSIA NI;
SOURCE 7 EXPRESSION_SYSTEM_TAXID: 7111
KEYWDS KINASE, TRANSFERASE-TRANSFERASE INHIBITOR COMPLEX
EXPDTA X-RAY DIFFRACTION
AUTHOR W.C.VOEGTLI
REVDAT 2 28-FEB-24 4EHG 1 REMARK SEQADV
REVDAT 1 24-APR-13 4EHG 0
JRNL AUTH S.MATHIEU,S.N.GRADL,L.REN,Z.WEN,I.ALIAGAS,J.GUNZNER-TOSTE,
JRNL AUTH 2 W.LEE,R.PULK,G.ZHAO,B.ALICKE,J.W.BOGGS,A.J.BUCKMELTER,
JRNL AUTH 3 E.F.CHOO,V.DINKEL,S.L.GLOOR,S.E.GOULD,J.D.HANSEN,G.HASTINGS,
JRNL AUTH 4 G.HATZIVASSILIOU,E.R.LAIRD,D.MORENO,Y.RAN,W.C.VOEGTLI,
JRNL AUTH 5 S.WENGLOWSKY,J.GRINA,J.RUDOLPH
JRNL TITL POTENT AND SELECTIVE AMINOPYRIMIDINE-BASED B-RAF INHIBITORS
JRNL TITL 2 WITH FAVORABLE PHYSICOCHEMICAL AND PHARMACOKINETIC
JRNL TITL 3 PROPERTIES.
JRNL REF J.MED.CHEM. V. 55 2869 2012
JRNL REFN ISSN 0022-2623
JRNL PMID 22335519
JRNL DOI 10.1021/JM300016V
REMARK 2
REMARK 2 RESOLUTION. 3.50 ANGSTROMS.
REMARK 3
REMARK 3 REFINEMENT.
REMARK 3 PROGRAM : REFMAC
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) : 3.50
REMARK 3 RESOLUTION RANGE LOW (ANGSTROMS) : 29.57
REMARK 3 DATA CUTOFF (SIGMA(F)) : 0.000
REMARK 3 COMPLETENESS FOR RANGE (%) : NULL
REMARK 3 NUMBER OF REFLECTIONS : 10158
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) : 0.215
REMARK 3 R VALUE (WORKING SET) : 0.212
REMARK 3 FREE R VALUE : 0.270
REMARK 3 FREE R VALUE TEST SET SIZE (%) : 4.800
REMARK 3 FREE R VALUE TEST SET COUNT : 511
REMARK 3
REMARK 3 FIT IN THE HIGHEST RESOLUTION BIN.
REMARK 3 TOTAL NUMBER OF BINS USED : 20
REMARK 3 BIN RESOLUTION RANGE HIGH (A) : 3.50
REMARK 3 BIN RESOLUTION RANGE LOW (A) : 3.59
REMARK 3 REFLECTION IN BIN (WORKING SET) : 774
REMARK 3 BIN COMPLETENESS (WORKING+TEST) (%) : 100.0
REMARK 3 BIN R VALUE (WORKING SET) : 0.2440
REMARK 3 BIN FREE R VALUE SET COUNT : 28
REMARK 3 BIN FREE R VALUE : 0.2400
REMARK 3
REMARK 3 NUMBER OF NON-HYDROGEN ATOMS USED IN REFINEMENT.
REMARK 3 PROTEIN ATOMS : 4175
REMARK 3 NUCLEIC ACID ATOMS : 0
REMARK 3 HETEROGEN ATOMS : 58
REMARK 3 SOLVENT ATOMS : 0
REMARK 3
REMARK 3 B VALUES.
REMARK 3 FROM WILSON PLOT (A**2) : NULL
REMARK 3 MEAN B VALUE (OVERALL, A**2) : 28.27
REMARK 3 OVERALL ANISOTROPIC B VALUE.
REMARK 3 B11 (A**2) : 0.07000
REMARK 3 B22 (A**2) : 0.07000
REMARK 3 B33 (A**2) : -0.14000
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): NULL
REMARK 3 ESU BASED ON FREE R VALUE (A): 0.620
REMARK 3 ESU BASED ON MAXIMUM LIKELIHOOD (A): 0.442
REMARK 3 ESU FOR B VALUES BASED ON MAXIMUM LIKELIHOOD (A**2): 27.670
REMARK 3
REMARK 3 CORRELATION COEFFICIENTS.
REMARK 3 CORRELATION COEFFICIENT FO-FC : 0.894
REMARK 3 CORRELATION COEFFICIENT FO-FC FREE : 0.814
REMARK 3
REMARK 3 RMS DEVIATIONS FROM IDEAL VALUES COUNT RMS WEIGHT
REMARK 3 BOND LENGTHS REFINED ATOMS (A): 4327 ; 0.012 ; 0.022
REMARK 3 BOND LENGTHS OTHERS (A): NULL ; NULL ; NULL
REMARK 3 BOND ANGLES REFINED ATOMS (DEGREES): 5841 ; 1.531 ; 1.978
REMARK 3 BOND ANGLES OTHERS (DEGREES): NULL ; NULL ; NULL
REMARK 3 TORSION ANGLES, PERIOD 1 (DEGREES): 518 ; 7.431 ; 5.000
REMARK 3 TORSION ANGLES, PERIOD 2 (DEGREES): 187 ;40.734 ;23.904
REMARK 3 TORSION ANGLES, PERIOD 3 (DEGREES): 790 ;21.601 ;15.000
REMARK 3 TORSION ANGLES, PERIOD 4 (DEGREES): 26 ;19.257 ;15.000
REMARK 3 CHIRAL-CENTER RESTRAINTS (A**3): 637 ; 0.104 ; 0.200
REMARK 3 GENERAL PLANES REFINED ATOMS (A): 3220 ; 0.004 ; 0.020
REMARK 3 GENERAL PLANES OTHERS (A): NULL ; NULL ; NULL
REMARK 3 NON-BONDED CONTACTS REFINED ATOMS (A): 2198 ; 0.248 ; 0.200
REMARK 3 NON-BONDED CONTACTS OTHERS (A): NULL ; NULL ; NULL
REMARK 3 NON-BONDED TORSION REFINED ATOMS (A): 2983 ; 0.322 ; 0.200
REMARK 3 NON-BONDED TORSION OTHERS (A): NULL ; NULL ; NULL
REMARK 3 H-BOND (X...Y) REFINED ATOMS (A): 156 ; 0.185 ; 0.200
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): 40 ; 0.215 ; 0.200
REMARK 3 SYMMETRY VDW OTHERS (A): NULL ; NULL ; NULL
REMARK 3 SYMMETRY H-BOND REFINED ATOMS (A): 5 ; 0.132 ; 0.200
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): 2650 ; 0.638 ; 1.500
REMARK 3 MAIN-CHAIN BOND OTHER ATOMS (A**2): NULL ; NULL ; NULL
REMARK 3 MAIN-CHAIN ANGLE REFINED ATOMS (A**2): 4202 ; 1.146 ; 2.000
REMARK 3 MAIN-CHAIN ANGLE OTHER ATOMS (A**2): NULL ; NULL ; NULL
REMARK 3 SIDE-CHAIN BOND REFINED ATOMS (A**2): 1896 ; 0.988 ; 3.000
REMARK 3 SIDE-CHAIN BOND OTHER ATOMS (A**2): NULL ; NULL ; NULL
REMARK 3 SIDE-CHAIN ANGLE REFINED ATOMS (A**2): 1639 ; 1.741 ; 4.500
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 : NULL
REMARK 3
REMARK 3 BULK SOLVENT MODELLING.
REMARK 3 METHOD USED : BABINET MODEL WITH 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: NULL
REMARK 4
REMARK 4 4EHG COMPLIES WITH FORMAT V. 3.30, 13-JUL-11
REMARK 100
REMARK 100 THIS ENTRY HAS BEEN PROCESSED BY RCSB ON 11-APR-12.
REMARK 100 THE DEPOSITION ID IS D_1000071622.
REMARK 200
REMARK 200 EXPERIMENTAL DETAILS
REMARK 200 EXPERIMENT TYPE : X-RAY DIFFRACTION
REMARK 200 DATE OF DATA COLLECTION : 15-JAN-09
REMARK 200 TEMPERATURE (KELVIN) : 100
REMARK 200 PH : 8.5
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) : 0.979
REMARK 200 MONOCHROMATOR : SINGLE CRYSTAL SI
REMARK 200 OPTICS : NULL
REMARK 200
REMARK 200 DETECTOR TYPE : CCD
REMARK 200 DETECTOR MANUFACTURER : ADSC QUANTUM 315R
REMARK 200 INTENSITY-INTEGRATION SOFTWARE : MOSFLM
REMARK 200 DATA SCALING SOFTWARE : SCALA
REMARK 200
REMARK 200 NUMBER OF UNIQUE REFLECTIONS : 10670
REMARK 200 RESOLUTION RANGE HIGH (A) : 3.500
REMARK 200 RESOLUTION RANGE LOW (A) : 30.000
REMARK 200 REJECTION CRITERIA (SIGMA(I)) : 0.000
REMARK 200
REMARK 200 OVERALL.
REMARK 200 COMPLETENESS FOR RANGE (%) : 98.4
REMARK 200 DATA REDUNDANCY : 3.800
REMARK 200 R MERGE (I) : 0.11900
REMARK 200 R SYM (I) : NULL
REMARK 200 <I/SIGMA(I)> FOR THE DATA SET : 5.8000
REMARK 200
REMARK 200 IN THE HIGHEST RESOLUTION SHELL.
REMARK 200 HIGHEST RESOLUTION SHELL, RANGE HIGH (A) : 3.50
REMARK 200 HIGHEST RESOLUTION SHELL, RANGE LOW (A) : 3.69
REMARK 200 COMPLETENESS FOR SHELL (%) : 99.7
REMARK 200 DATA REDUNDANCY IN SHELL : 3.80
REMARK 200 R MERGE FOR SHELL (I) : 0.26000
REMARK 200 R SYM FOR SHELL (I) : NULL
REMARK 200 <I/SIGMA(I)> FOR SHELL : 2.800
REMARK 200
REMARK 200 DIFFRACTION PROTOCOL: SINGLE WAVELENGTH
REMARK 200 METHOD USED TO DETERMINE THE STRUCTURE: MOLECULAR REPLACEMENT
REMARK 200 SOFTWARE USED: REFMAC
REMARK 200 STARTING MODEL: NULL
REMARK 200
REMARK 200 REMARK: NULL
REMARK 280
REMARK 280 CRYSTAL
REMARK 280 SOLVENT CONTENT, VS (%): 57.42
REMARK 280 MATTHEWS COEFFICIENT, VM (ANGSTROMS**3/DA): 2.89
REMARK 280
REMARK 280 CRYSTALLIZATION CONDITIONS: 12% PEG 8000, 400 MM AMMONIUM SULFATE,
REMARK 280 100 MM MES/MALIC ACID/ TRIS, PH 8.5, VAPOR DIFFUSION, HANGING
REMARK 280 DROP, TEMPERATURE 293K
REMARK 290
REMARK 290 CRYSTALLOGRAPHIC SYMMETRY
REMARK 290 SYMMETRY OPERATORS FOR SPACE GROUP: P 41 21 2
REMARK 290
REMARK 290 SYMOP SYMMETRY
REMARK 290 NNNMMM OPERATOR
REMARK 290 1555 X,Y,Z
REMARK 290 2555 -X,-Y,Z+1/2
REMARK 290 3555 -Y+1/2,X+1/2,Z+1/4
REMARK 290 4555 Y+1/2,-X+1/2,Z+3/4
REMARK 290 5555 -X+1/2,Y+1/2,-Z+1/4
REMARK 290 6555 X+1/2,-Y+1/2,-Z+3/4
REMARK 290 7555 Y,X,-Z
REMARK 290 8555 -Y,-X,-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 80.65250
REMARK 290 SMTRY1 3 0.000000 -1.000000 0.000000 50.24950
REMARK 290 SMTRY2 3 1.000000 0.000000 0.000000 50.24950
REMARK 290 SMTRY3 3 0.000000 0.000000 1.000000 40.32625
REMARK 290 SMTRY1 4 0.000000 1.000000 0.000000 50.24950
REMARK 290 SMTRY2 4 -1.000000 0.000000 0.000000 50.24950
REMARK 290 SMTRY3 4 0.000000 0.000000 1.000000 120.97875
REMARK 290 SMTRY1 5 -1.000000 0.000000 0.000000 50.24950
REMARK 290 SMTRY2 5 0.000000 1.000000 0.000000 50.24950
REMARK 290 SMTRY3 5 0.000000 0.000000 -1.000000 40.32625
REMARK 290 SMTRY1 6 1.000000 0.000000 0.000000 50.24950
REMARK 290 SMTRY2 6 0.000000 -1.000000 0.000000 50.24950
REMARK 290 SMTRY3 6 0.000000 0.000000 -1.000000 120.97875
REMARK 290 SMTRY1 7 0.000000 1.000000 0.000000 0.00000
REMARK 290 SMTRY2 7 1.000000 0.000000 0.000000 0.00000
REMARK 290 SMTRY3 7 0.000000 0.000000 -1.000000 0.00000
REMARK 290 SMTRY1 8 0.000000 -1.000000 0.000000 0.00000
REMARK 290 SMTRY2 8 -1.000000 0.000000 0.000000 0.00000
REMARK 290 SMTRY3 8 0.000000 0.000000 -1.000000 80.65250
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 AUTHOR DETERMINED BIOLOGICAL UNIT: DIMERIC
REMARK 350 SOFTWARE DETERMINED QUATERNARY STRUCTURE: DIMERIC
REMARK 350 SOFTWARE USED: PISA
REMARK 350 TOTAL BURIED SURFACE AREA: 2170 ANGSTROM**2
REMARK 350 SURFACE AREA OF THE COMPLEX: 24320 ANGSTROM**2
REMARK 350 CHANGE IN SOLVENT FREE ENERGY: -8.0 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 MET A 420
REMARK 465 ASP A 421
REMARK 465 ARG A 422
REMARK 465 GLY A 423
REMARK 465 SER A 424
REMARK 465 HIS A 425
REMARK 465 HIS A 426
REMARK 465 HIS A 427
REMARK 465 HIS A 428
REMARK 465 HIS A 429
REMARK 465 HIS A 430
REMARK 465 GLY A 431
REMARK 465 SER A 432
REMARK 465 GLU A 433
REMARK 465 ASP A 434
REMARK 465 ARG A 435
REMARK 465 ASN A 436
REMARK 465 ARG A 437
REMARK 465 MET A 438
REMARK 465 LYS A 439
REMARK 465 THR A 440
REMARK 465 LEU A 441
REMARK 465 GLY A 442
REMARK 465 ARG A 443
REMARK 465 ARG A 444
REMARK 465 ASP A 445
REMARK 465 SER A 446
REMARK 465 SER A 447
REMARK 465 LYS A 601
REMARK 465 SER A 602
REMARK 465 ARG A 603
REMARK 465 TRP A 604
REMARK 465 SER A 605
REMARK 465 GLY A 606
REMARK 465 SER A 607
REMARK 465 HIS A 608
REMARK 465 GLN A 609
REMARK 465 PHE A 610
REMARK 465 GLU A 611
REMARK 465 GLN A 612
REMARK 465 LEU A 613
REMARK 465 SER A 614
REMARK 465 ILE A 724
REMARK 465 HIS A 725
REMARK 465 ARG A 726
REMARK 465 MET B 420
REMARK 465 ASP B 421
REMARK 465 ARG B 422
REMARK 465 GLY B 423
REMARK 465 SER B 424
REMARK 465 HIS B 425
REMARK 465 HIS B 426
REMARK 465 HIS B 427
REMARK 465 HIS B 428
REMARK 465 HIS B 429
REMARK 465 HIS B 430
REMARK 465 GLY B 431
REMARK 465 SER B 432
REMARK 465 GLU B 433
REMARK 465 ASP B 434
REMARK 465 ARG B 435
REMARK 465 ASN B 436
REMARK 465 ARG B 437
REMARK 465 MET B 438
REMARK 465 LYS B 439
REMARK 465 THR B 440
REMARK 465 LEU B 441
REMARK 465 GLY B 442
REMARK 465 ARG B 443
REMARK 465 ARG B 444
REMARK 465 ASP B 445
REMARK 465 SER B 446
REMARK 465 SER B 447
REMARK 465 ALA B 598
REMARK 465 THR B 599
REMARK 465 GLU B 600
REMARK 465 LYS B 601
REMARK 465 SER B 602
REMARK 465 ARG B 603
REMARK 465 TRP B 604
REMARK 465 SER B 605
REMARK 465 GLY B 606
REMARK 465 SER B 607
REMARK 465 HIS B 608
REMARK 465 GLN B 609
REMARK 465 PHE B 610
REMARK 465 GLU B 611
REMARK 465 GLN B 612
REMARK 465 LEU B 613
REMARK 465 ILE B 724
REMARK 465 HIS B 725
REMARK 465 ARG B 726
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 O ASP A 576 ND2 ASN A 581 2.11
REMARK 500
REMARK 500 REMARK: NULL
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 LEU B 495 CA - CB - CG ANGL. DEV. = 13.8 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 449 131.85 -32.99
REMARK 500 SER A 467 85.04 38.97
REMARK 500 TRP A 476 106.48 -165.55
REMARK 500 LEU A 485 42.40 -68.50
REMARK 500 ASN A 486 78.95 -32.12
REMARK 500 ALA A 489 87.13 42.13
REMARK 500 THR A 491 33.94 84.39
REMARK 500 GLN A 493 68.88 -114.47
REMARK 500 ARG A 506 -5.08 -56.50
REMARK 500 LYS A 522 -70.45 -54.34
REMARK 500 ARG A 575 -24.44 63.93
REMARK 500 ASP A 576 56.82 -141.25
REMARK 500 GLU A 586 39.39 36.99
REMARK 500 LEU A 588 -8.99 -165.38
REMARK 500 ASP A 594 70.69 73.83
REMARK 500 PHE A 595 -9.00 -143.13
REMARK 500 LEU A 597 -87.95 57.49
REMARK 500 ALA A 598 55.57 10.50
REMARK 500 GLN A 628 -94.48 38.35
REMARK 500 SER A 657 -18.69 -47.59
REMARK 500 SER A 679 -12.67 -46.12
REMARK 500 SER A 683 -32.51 -32.56
REMARK 500 SER A 720 33.99 -73.89
REMARK 500 LEU A 721 -54.63 -147.76
REMARK 500 GLN B 461 116.18 -10.84
REMARK 500 ILE B 463 -58.98 -147.32
REMARK 500 SER B 465 -106.34 -91.97
REMARK 500 SER B 467 -23.39 -153.22
REMARK 500 TRP B 476 102.27 -174.57
REMARK 500 ASN B 486 55.14 33.06
REMARK 500 THR B 488 152.64 -47.42
REMARK 500 THR B 491 33.35 97.73
REMARK 500 LEU B 514 123.93 -37.31
REMARK 500 GLN B 524 146.79 164.10
REMARK 500 ARG B 575 -6.56 68.62
REMARK 500 ASP B 576 47.96 -165.30
REMARK 500 GLU B 586 24.57 49.12
REMARK 500 SER B 616 72.39 -164.62
REMARK 500 ILE B 625 -70.71 -49.88
REMARK 500 MET B 627 51.81 -101.38
REMARK 500 ASP B 629 -141.05 -148.06
REMARK 500 TYR B 656 18.01 55.37
REMARK 500 SER B 657 -16.99 -39.58
REMARK 500 SER B 683 -61.77 34.17
REMARK 500 LYS B 698 130.42 -34.06
REMARK 500 LEU B 721 49.35 -159.68
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 RI9 A 801
REMARK 800
REMARK 800 SITE_IDENTIFIER: AC2
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: BINDING SITE FOR RESIDUE RI9 B 801
REMARK 900
REMARK 900 RELATED ENTRIES
REMARK 900 RELATED ID: 4EHE RELATED DB: PDB
DBREF 4EHG A 432 726 UNP P15056 BRAF_HUMAN 432 726
DBREF 4EHG B 432 726 UNP P15056 BRAF_HUMAN 432 726
SEQADV 4EHG MET A 420 UNP P15056 EXPRESSION TAG
SEQADV 4EHG ASP A 421 UNP P15056 EXPRESSION TAG
SEQADV 4EHG ARG A 422 UNP P15056 EXPRESSION TAG
SEQADV 4EHG GLY A 423 UNP P15056 EXPRESSION TAG
SEQADV 4EHG SER A 424 UNP P15056 EXPRESSION TAG
SEQADV 4EHG HIS A 425 UNP P15056 EXPRESSION TAG
SEQADV 4EHG HIS A 426 UNP P15056 EXPRESSION TAG
SEQADV 4EHG HIS A 427 UNP P15056 EXPRESSION TAG
SEQADV 4EHG HIS A 428 UNP P15056 EXPRESSION TAG
SEQADV 4EHG HIS A 429 UNP P15056 EXPRESSION TAG
SEQADV 4EHG HIS A 430 UNP P15056 EXPRESSION TAG
SEQADV 4EHG GLY A 431 UNP P15056 EXPRESSION TAG
SEQADV 4EHG GLU A 600 UNP P15056 VAL 600 ENGINEERED MUTATION
SEQADV 4EHG MET B 420 UNP P15056 EXPRESSION TAG
SEQADV 4EHG ASP B 421 UNP P15056 EXPRESSION TAG
SEQADV 4EHG ARG B 422 UNP P15056 EXPRESSION TAG
SEQADV 4EHG GLY B 423 UNP P15056 EXPRESSION TAG
SEQADV 4EHG SER B 424 UNP P15056 EXPRESSION TAG
SEQADV 4EHG HIS B 425 UNP P15056 EXPRESSION TAG
SEQADV 4EHG HIS B 426 UNP P15056 EXPRESSION TAG
SEQADV 4EHG HIS B 427 UNP P15056 EXPRESSION TAG
SEQADV 4EHG HIS B 428 UNP P15056 EXPRESSION TAG
SEQADV 4EHG HIS B 429 UNP P15056 EXPRESSION TAG
SEQADV 4EHG HIS B 430 UNP P15056 EXPRESSION TAG
SEQADV 4EHG GLY B 431 UNP P15056 EXPRESSION TAG
SEQADV 4EHG GLU B 600 UNP P15056 VAL 600 ENGINEERED MUTATION
SEQRES 1 A 307 MET ASP ARG GLY SER HIS HIS HIS HIS HIS HIS GLY SER
SEQRES 2 A 307 GLU ASP ARG ASN ARG MET LYS THR LEU GLY ARG ARG ASP
SEQRES 3 A 307 SER SER ASP ASP TRP GLU ILE PRO ASP GLY GLN ILE THR
SEQRES 4 A 307 VAL GLY GLN ARG ILE GLY SER GLY SER PHE GLY THR VAL
SEQRES 5 A 307 TYR LYS GLY LYS TRP HIS GLY ASP VAL ALA VAL LYS MET
SEQRES 6 A 307 LEU ASN VAL THR ALA PRO THR PRO GLN GLN LEU GLN ALA
SEQRES 7 A 307 PHE LYS ASN GLU VAL GLY VAL LEU ARG LYS THR ARG HIS
SEQRES 8 A 307 VAL ASN ILE LEU LEU PHE MET GLY TYR SER THR LYS PRO
SEQRES 9 A 307 GLN LEU ALA ILE VAL THR GLN TRP CYS GLU GLY SER SER
SEQRES 10 A 307 LEU TYR HIS HIS LEU HIS ILE ILE GLU THR LYS PHE GLU
SEQRES 11 A 307 MET ILE LYS LEU ILE ASP ILE ALA ARG GLN THR ALA GLN
SEQRES 12 A 307 GLY MET ASP TYR LEU HIS ALA LYS SER ILE ILE HIS ARG
SEQRES 13 A 307 ASP LEU LYS SER ASN ASN ILE PHE LEU HIS GLU ASP LEU
SEQRES 14 A 307 THR VAL LYS ILE GLY ASP PHE GLY LEU ALA THR GLU LYS
SEQRES 15 A 307 SER ARG TRP SER GLY SER HIS GLN PHE GLU GLN LEU SER
SEQRES 16 A 307 GLY SER ILE LEU TRP MET ALA PRO GLU VAL ILE ARG MET
SEQRES 17 A 307 GLN ASP LYS ASN PRO TYR SER PHE GLN SER ASP VAL TYR
SEQRES 18 A 307 ALA PHE GLY ILE VAL LEU TYR GLU LEU MET THR GLY GLN
SEQRES 19 A 307 LEU PRO TYR SER ASN ILE ASN ASN ARG ASP GLN ILE ILE
SEQRES 20 A 307 PHE MET VAL GLY ARG GLY TYR LEU SER PRO ASP LEU SER
SEQRES 21 A 307 LYS VAL ARG SER ASN CYS PRO LYS ALA MET LYS ARG LEU
SEQRES 22 A 307 MET ALA GLU CYS LEU LYS LYS LYS ARG ASP GLU ARG PRO
SEQRES 23 A 307 LEU PHE PRO GLN ILE LEU ALA SER ILE GLU LEU LEU ALA
SEQRES 24 A 307 ARG SER LEU PRO LYS ILE HIS ARG
SEQRES 1 B 307 MET ASP ARG GLY SER HIS HIS HIS HIS HIS HIS GLY SER
SEQRES 2 B 307 GLU ASP ARG ASN ARG MET LYS THR LEU GLY ARG ARG ASP
SEQRES 3 B 307 SER SER ASP ASP TRP GLU ILE PRO ASP GLY GLN ILE THR
SEQRES 4 B 307 VAL GLY GLN ARG ILE GLY SER GLY SER PHE GLY THR VAL
SEQRES 5 B 307 TYR LYS GLY LYS TRP HIS GLY ASP VAL ALA VAL LYS MET
SEQRES 6 B 307 LEU ASN VAL THR ALA PRO THR PRO GLN GLN LEU GLN ALA
SEQRES 7 B 307 PHE LYS ASN GLU VAL GLY VAL LEU ARG LYS THR ARG HIS
SEQRES 8 B 307 VAL ASN ILE LEU LEU PHE MET GLY TYR SER THR LYS PRO
SEQRES 9 B 307 GLN LEU ALA ILE VAL THR GLN TRP CYS GLU GLY SER SER
SEQRES 10 B 307 LEU TYR HIS HIS LEU HIS ILE ILE GLU THR LYS PHE GLU
SEQRES 11 B 307 MET ILE LYS LEU ILE ASP ILE ALA ARG GLN THR ALA GLN
SEQRES 12 B 307 GLY MET ASP TYR LEU HIS ALA LYS SER ILE ILE HIS ARG
SEQRES 13 B 307 ASP LEU LYS SER ASN ASN ILE PHE LEU HIS GLU ASP LEU
SEQRES 14 B 307 THR VAL LYS ILE GLY ASP PHE GLY LEU ALA THR GLU LYS
SEQRES 15 B 307 SER ARG TRP SER GLY SER HIS GLN PHE GLU GLN LEU SER
SEQRES 16 B 307 GLY SER ILE LEU TRP MET ALA PRO GLU VAL ILE ARG MET
SEQRES 17 B 307 GLN ASP LYS ASN PRO TYR SER PHE GLN SER ASP VAL TYR
SEQRES 18 B 307 ALA PHE GLY ILE VAL LEU TYR GLU LEU MET THR GLY GLN
SEQRES 19 B 307 LEU PRO TYR SER ASN ILE ASN ASN ARG ASP GLN ILE ILE
SEQRES 20 B 307 PHE MET VAL GLY ARG GLY TYR LEU SER PRO ASP LEU SER
SEQRES 21 B 307 LYS VAL ARG SER ASN CYS PRO LYS ALA MET LYS ARG LEU
SEQRES 22 B 307 MET ALA GLU CYS LEU LYS LYS LYS ARG ASP GLU ARG PRO
SEQRES 23 B 307 LEU PHE PRO GLN ILE LEU ALA SER ILE GLU LEU LEU ALA
SEQRES 24 B 307 ARG SER LEU PRO LYS ILE HIS ARG
HET RI9 A 801 29
HET RI9 B 801 29
HETNAM RI9 N-{2,4-DIFLUORO-3-[({6-[(2-HYDROXYETHYL)
HETNAM 2 RI9 AMINO]PYRIMIDIN-4-YL}CARBAMOYL)AMINO]PHENYL}PROPANE-1-
HETNAM 3 RI9 SULFONAMIDE
FORMUL 3 RI9 2(C16 H20 F2 N6 O4 S)
HELIX 1 1 GLN A 493 ARG A 506 1 14
HELIX 2 2 LEU A 537 ILE A 543 1 7
HELIX 3 3 GLU A 549 LYS A 570 1 22
HELIX 4 4 ALA A 621 ARG A 626 1 6
HELIX 5 5 SER A 634 GLY A 652 1 19
HELIX 6 6 ASN A 661 ARG A 671 1 11
HELIX 7 7 ASP A 677 VAL A 681 5 5
HELIX 8 8 PRO A 686 LEU A 697 1 12
HELIX 9 9 LYS A 700 ARG A 704 5 5
HELIX 10 10 LEU A 706 SER A 720 1 15
HELIX 11 11 GLN B 494 ARG B 506 1 13
HELIX 12 12 LEU B 537 ILE B 543 1 7
HELIX 13 13 GLU B 549 LYS B 570 1 22
HELIX 14 14 LYS B 578 ASN B 580 5 3
HELIX 15 15 ALA B 621 ARG B 626 1 6
HELIX 16 16 SER B 634 GLY B 652 1 19
HELIX 17 17 ASN B 661 GLY B 672 1 12
HELIX 18 18 ASP B 677 VAL B 681 5 5
HELIX 19 19 PRO B 686 LYS B 698 1 13
HELIX 20 20 LYS B 700 ARG B 704 5 5
HELIX 21 21 LEU B 706 SER B 720 1 15
SHEET 1 A 5 THR A 458 GLY A 466 0
SHEET 2 A 5 GLY A 469 LYS A 475 -1 O VAL A 471 N ILE A 463
SHEET 3 A 5 ASP A 479 MET A 484 -1 O VAL A 480 N GLY A 474
SHEET 4 A 5 ALA A 526 GLN A 530 -1 O THR A 529 N ALA A 481
SHEET 5 A 5 PHE A 516 SER A 520 -1 N GLY A 518 O VAL A 528
SHEET 1 B 3 GLY A 534 SER A 536 0
SHEET 2 B 3 ILE A 582 HIS A 585 -1 O LEU A 584 N SER A 535
SHEET 3 B 3 THR A 589 ILE A 592 -1 O THR A 589 N HIS A 585
SHEET 1 C 4 THR B 470 LYS B 475 0
SHEET 2 C 4 ASP B 479 MET B 484 -1 O VAL B 480 N GLY B 474
SHEET 3 C 4 ALA B 526 GLN B 530 -1 O ILE B 527 N LYS B 483
SHEET 4 C 4 PHE B 516 SER B 520 -1 N GLY B 518 O VAL B 528
SHEET 1 D 3 GLY B 534 SER B 536 0
SHEET 2 D 3 ILE B 582 HIS B 585 -1 O LEU B 584 N SER B 535
SHEET 3 D 3 THR B 589 ILE B 592 -1 O LYS B 591 N PHE B 583
CISPEP 1 PRO A 490 THR A 491 0 23.51
CISPEP 2 PRO A 492 GLN A 493 0 1.10
CISPEP 3 THR A 599 GLU A 600 0 5.11
CISPEP 4 PRO B 490 THR B 491 0 23.91
CISPEP 5 PRO B 492 GLN B 493 0 4.56
SITE 1 AC1 14 ALA A 481 VAL A 482 LYS A 483 LEU A 514
SITE 2 AC1 14 ILE A 527 GLN A 530 TRP A 531 CYS A 532
SITE 3 AC1 14 GLY A 534 PHE A 583 ASP A 594 PHE A 595
SITE 4 AC1 14 GLY A 596 ARG B 671
SITE 1 AC2 15 ALA B 481 VAL B 482 LYS B 483 LEU B 505
SITE 2 AC2 15 LEU B 514 THR B 529 GLN B 530 TRP B 531
SITE 3 AC2 15 CYS B 532 GLY B 534 SER B 535 PHE B 583
SITE 4 AC2 15 ASP B 594 PHE B 595 GLY B 596
CRYST1 100.499 100.499 161.305 90.00 90.00 90.00 P 41 21 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 0.009950 0.000000 0.000000 0.00000
SCALE2 0.000000 0.009950 0.000000 0.00000
SCALE3 0.000000 0.000000 0.006199 0.00000
(ATOM LINES ARE NOT SHOWN.)
END
