HEADER TRANSFERASE/TRANSFERASE INHIBITOR 23-JUL-12 4G9C
TITLE HUMAN B-RAF KINASE DOMAIN BOUND TO A TYPE II PYRAZOLOPYRIDINE
TITLE 2 INHIBITOR
COMPND MOL_ID: 1;
COMPND 2 MOLECULE: SERINE/THREONINE-PROTEIN KINASE B-RAF;
COMPND 3 CHAIN: A, B;
COMPND 4 FRAGMENT: KINASE DOMAIN (UNP RESIDUES 432-726);
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
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;
SOURCE 8 EXPRESSION_SYSTEM_STRAIN: HIGH FIVE
KEYWDS DFG-OUT, INHIBITOR, TYPE II, TRANSFERASE, KINASE, TRANSFERASE-
KEYWDS 2 TRANSFERASE INHIBITOR COMPLEX
EXPDTA X-RAY DIFFRACTION
AUTHOR W.C.VOEGTLI,H.L.STURGIS
REVDAT 2 28-FEB-24 4G9C 1 REMARK SEQADV
REVDAT 1 14-NOV-12 4G9C 0
JRNL AUTH S.WENGLOWSKY,D.MORENO,E.R.LAIRD,S.L.GLOOR,L.REN,T.RISOM,
JRNL AUTH 2 J.RUDOLPH,H.L.STURGIS,W.C.VOEGTLI
JRNL TITL PYRAZOLOPYRIDINE INHIBITORS OF B-RAF(V600E). PART 4:
JRNL TITL 2 RATIONAL DESIGN AND KINASE SELECTIVITY PROFILE OF CELL
JRNL TITL 3 POTENT TYPE II INHIBITORS.
JRNL REF BIOORG.MED.CHEM.LETT. V. 22 6237 2012
JRNL REFN ISSN 0960-894X
JRNL PMID 22954737
JRNL DOI 10.1016/J.BMCL.2012.08.007
REMARK 2
REMARK 2 RESOLUTION. 3.50 ANGSTROMS.
REMARK 3
REMARK 3 REFINEMENT.
REMARK 3 PROGRAM : CNS
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 DATA USED IN REFINEMENT.
REMARK 3 RESOLUTION RANGE HIGH (ANGSTROMS) : 3.50
REMARK 3 RESOLUTION RANGE LOW (ANGSTROMS) : 29.76
REMARK 3 DATA CUTOFF (SIGMA(F)) : 0.000
REMARK 3 DATA CUTOFF HIGH (ABS(F)) : 4777125.660
REMARK 3 DATA CUTOFF LOW (ABS(F)) : 0.0000
REMARK 3 COMPLETENESS (WORKING+TEST) (%) : 95.3
REMARK 3 NUMBER OF REFLECTIONS : 11851
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) : 0.262
REMARK 3 R VALUE (WORKING SET) : 0.260
REMARK 3 FREE R VALUE : 0.291
REMARK 3 FREE R VALUE TEST SET SIZE (%) : 6.100
REMARK 3 FREE R VALUE TEST SET COUNT : 723
REMARK 3 ESTIMATED ERROR OF FREE R VALUE : 0.011
REMARK 3
REMARK 3 FIT/AGREEMENT OF MODEL WITH ALL DATA.
REMARK 3 R VALUE (WORKING + TEST SET, NO CUTOFF) : 0.2740
REMARK 3 R VALUE (WORKING SET, NO CUTOFF) : 0.2720
REMARK 3 FREE R VALUE (NO CUTOFF) : 0.303
REMARK 3 FREE R VALUE TEST SET SIZE (%, NO CUTOFF) : 6.100
REMARK 3 FREE R VALUE TEST SET COUNT (NO CUTOFF) : 723
REMARK 3 ESTIMATED ERROR OF FREE R VALUE (NO CUTOFF) : 0.0110
REMARK 3 TOTAL NUMBER OF REFLECTIONS (NO CUTOFF) : 11851
REMARK 3
REMARK 3 FIT IN THE HIGHEST RESOLUTION BIN.
REMARK 3 TOTAL NUMBER OF BINS USED : 6
REMARK 3 BIN RESOLUTION RANGE HIGH (A) : 3.50
REMARK 3 BIN RESOLUTION RANGE LOW (A) : 3.72
REMARK 3 BIN COMPLETENESS (WORKING+TEST) (%) : 96.80
REMARK 3 REFLECTIONS IN BIN (WORKING SET) : 1831
REMARK 3 BIN R VALUE (WORKING SET) : 0.2960
REMARK 3 BIN FREE R VALUE : 0.3360
REMARK 3 BIN FREE R VALUE TEST SET SIZE (%) : 6.00
REMARK 3 BIN FREE R VALUE TEST SET COUNT : 117
REMARK 3 ESTIMATED ERROR OF BIN FREE R VALUE : 0.031
REMARK 3
REMARK 3 NUMBER OF NON-HYDROGEN ATOMS USED IN REFINEMENT.
REMARK 3 PROTEIN ATOMS : 4215
REMARK 3 NUCLEIC ACID ATOMS : 0
REMARK 3 HETEROGEN ATOMS : 72
REMARK 3 SOLVENT ATOMS : 0
REMARK 3
REMARK 3 B VALUES.
REMARK 3 FROM WILSON PLOT (A**2) : 155.5
REMARK 3 MEAN B VALUE (OVERALL, A**2) : 52.20
REMARK 3 OVERALL ANISOTROPIC B VALUE.
REMARK 3 B11 (A**2) : -9.14000
REMARK 3 B22 (A**2) : -9.14000
REMARK 3 B33 (A**2) : 18.29000
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) : 0.40
REMARK 3 ESD FROM SIGMAA (A) : 0.50
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) : 0.47
REMARK 3 ESD FROM C-V SIGMAA (A) : 0.52
REMARK 3
REMARK 3 RMS DEVIATIONS FROM IDEAL VALUES.
REMARK 3 BOND LENGTHS (A) : 0.007
REMARK 3 BOND ANGLES (DEGREES) : 0.900
REMARK 3 DIHEDRAL ANGLES (DEGREES) : 22.60
REMARK 3 IMPROPER ANGLES (DEGREES) : 0.600
REMARK 3
REMARK 3 ISOTROPIC THERMAL MODEL : RESTRAINED
REMARK 3
REMARK 3 ISOTROPIC THERMAL FACTOR RESTRAINTS. RMS SIGMA
REMARK 3 MAIN-CHAIN BOND (A**2) : 1.700 ; 1.500
REMARK 3 MAIN-CHAIN ANGLE (A**2) : 3.150 ; 2.000
REMARK 3 SIDE-CHAIN BOND (A**2) : 1.500 ; 2.000
REMARK 3 SIDE-CHAIN ANGLE (A**2) : 2.660 ; 2.500
REMARK 3
REMARK 3 BULK SOLVENT MODELING.
REMARK 3 METHOD USED : FLAT MODEL
REMARK 3 KSOL : 0.31
REMARK 3 BSOL : 43.67
REMARK 3
REMARK 3 NCS MODEL : CONSTR
REMARK 3
REMARK 3 NCS RESTRAINTS. RMS SIGMA/WEIGHT
REMARK 3 GROUP 1 POSITIONAL (A) : NULL ; NULL
REMARK 3 GROUP 1 B-FACTOR (A**2) : NULL ; NULL
REMARK 3
REMARK 3 PARAMETER FILE 1 : PROTEIN_REP.PARA
REMARK 3 PARAMETER FILE 2 : AR00460174.PAR
REMARK 3 PARAMETER FILE 3 : NULL
REMARK 3 TOPOLOGY FILE 1 : PROTEIN.TOP
REMARK 3 TOPOLOGY FILE 2 : AR00460174.TOP
REMARK 3 TOPOLOGY FILE 3 : NULL
REMARK 3
REMARK 3 OTHER REFINEMENT REMARKS: NULL
REMARK 4
REMARK 4 4G9C COMPLIES WITH FORMAT V. 3.30, 13-JUL-11
REMARK 100
REMARK 100 THIS ENTRY HAS BEEN PROCESSED BY RCSB ON 27-JUL-12.
REMARK 100 THE DEPOSITION ID IS D_1000073901.
REMARK 200
REMARK 200 EXPERIMENTAL DETAILS
REMARK 200 EXPERIMENT TYPE : X-RAY DIFFRACTION
REMARK 200 DATE OF DATA COLLECTION : 22-JUL-08
REMARK 200 TEMPERATURE (KELVIN) : 100
REMARK 200 PH : 9.0
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 : SYNCHROTRON SILICON CRYSTAL
REMARK 200 OPTICS : NULL
REMARK 200
REMARK 200 DETECTOR TYPE : CCD
REMARK 200 DETECTOR MANUFACTURER : ADSC QUANTUM 315
REMARK 200 INTENSITY-INTEGRATION SOFTWARE : MOSFLM
REMARK 200 DATA SCALING SOFTWARE : SCALA
REMARK 200
REMARK 200 NUMBER OF UNIQUE REFLECTIONS : 11862
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 (%) : 96.5
REMARK 200 DATA REDUNDANCY : 3.100
REMARK 200 R MERGE (I) : 0.11100
REMARK 200 R SYM (I) : NULL
REMARK 200 <I/SIGMA(I)> FOR THE DATA SET : 6.2000
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 (%) : 97.4
REMARK 200 DATA REDUNDANCY IN SHELL : 3.20
REMARK 200 R MERGE FOR SHELL (I) : 0.36900
REMARK 200 R SYM FOR SHELL (I) : NULL
REMARK 200 <I/SIGMA(I)> FOR SHELL : 2.000
REMARK 200
REMARK 200 DIFFRACTION PROTOCOL: SINGLE WAVELENGTH
REMARK 200 METHOD USED TO DETERMINE THE STRUCTURE: MOLECULAR REPLACEMENT
REMARK 200 SOFTWARE USED: CNS
REMARK 200 STARTING MODEL: NULL
REMARK 200
REMARK 200 REMARK: NULL
REMARK 280
REMARK 280 CRYSTAL
REMARK 280 SOLVENT CONTENT, VS (%): 62.63
REMARK 280 MATTHEWS COEFFICIENT, VM (ANGSTROMS**3/DA): 3.29
REMARK 280
REMARK 280 CRYSTALLIZATION CONDITIONS: 100 MM TRIS PH 9.0, PEG 8000, VAPOR
REMARK 280 DIFFUSION, HANGING 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 80.92500
REMARK 290 SMTRY1 3 0.000000 -1.000000 0.000000 53.52500
REMARK 290 SMTRY2 3 1.000000 0.000000 0.000000 53.52500
REMARK 290 SMTRY3 3 0.000000 0.000000 1.000000 40.46250
REMARK 290 SMTRY1 4 0.000000 1.000000 0.000000 53.52500
REMARK 290 SMTRY2 4 -1.000000 0.000000 0.000000 53.52500
REMARK 290 SMTRY3 4 0.000000 0.000000 1.000000 121.38750
REMARK 290 SMTRY1 5 -1.000000 0.000000 0.000000 53.52500
REMARK 290 SMTRY2 5 0.000000 1.000000 0.000000 53.52500
REMARK 290 SMTRY3 5 0.000000 0.000000 -1.000000 40.46250
REMARK 290 SMTRY1 6 1.000000 0.000000 0.000000 53.52500
REMARK 290 SMTRY2 6 0.000000 -1.000000 0.000000 53.52500
REMARK 290 SMTRY3 6 0.000000 0.000000 -1.000000 121.38750
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 80.92500
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 300 REMARK: PROTEIN EXISTS IN AN EQUILIBRIUM BETWEEN MONOMER AND DIMER
REMARK 300 STATE IN SOLUTION
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 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 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 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 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 ILE B 724
REMARK 465 HIS B 725
REMARK 465 ARG B 726
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 522 CG CD CE NZ
REMARK 470 LYS B 522 CG 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 TRP A 476 92.97 -164.45
REMARK 500 ARG A 509 93.10 -166.32
REMARK 500 LYS A 522 167.19 -43.07
REMARK 500 PRO A 523 97.48 -21.35
REMARK 500 GLN A 524 -26.57 114.35
REMARK 500 LEU A 525 118.07 83.05
REMARK 500 GLN A 530 154.67 -48.28
REMARK 500 ILE A 543 -67.21 -103.96
REMARK 500 ASP A 576 31.92 -162.46
REMARK 500 ASP A 587 -14.84 78.31
REMARK 500 THR A 589 79.82 59.79
REMARK 500 ASP A 594 68.22 -114.62
REMARK 500 THR A 599 66.08 89.35
REMARK 500 VAL A 600 -92.17 77.81
REMARK 500 SER A 614 -116.68 -63.56
REMARK 500 MET A 627 60.79 71.75
REMARK 500 GLN A 628 -91.55 -62.40
REMARK 500 ASP A 629 43.71 -100.70
REMARK 500 LYS A 630 -38.02 68.04
REMARK 500 LEU A 721 10.06 -170.81
REMARK 500 PRO A 722 -9.99 -56.15
REMARK 500 ILE B 463 -68.85 -95.38
REMARK 500 TRP B 476 91.56 -165.70
REMARK 500 ARG B 509 92.87 -166.42
REMARK 500 LYS B 522 167.04 -44.17
REMARK 500 PRO B 523 97.60 -21.47
REMARK 500 GLN B 524 -27.09 113.37
REMARK 500 LEU B 525 117.34 83.30
REMARK 500 GLN B 530 154.13 -47.37
REMARK 500 ILE B 543 -67.80 -103.75
REMARK 500 ARG B 575 -0.43 78.89
REMARK 500 ASP B 576 31.05 -162.01
REMARK 500 ASP B 587 -15.10 76.67
REMARK 500 THR B 589 79.33 59.46
REMARK 500 ASP B 594 70.68 -114.09
REMARK 500 LEU B 597 -87.03 -102.49
REMARK 500 THR B 599 151.53 73.00
REMARK 500 SER B 614 -116.41 -65.14
REMARK 500 MET B 627 61.09 71.50
REMARK 500 GLN B 628 -90.33 -62.51
REMARK 500 ASP B 629 44.09 -101.52
REMARK 500 LYS B 630 -37.80 67.41
REMARK 500 LEU B 721 10.02 -171.46
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 LEU B 597 ALA B 598 101.50
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 0WP A 801
REMARK 800
REMARK 800 SITE_IDENTIFIER: AC2
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: BINDING SITE FOR RESIDUE 0WP B 801
REMARK 900
REMARK 900 RELATED ENTRIES
REMARK 900 RELATED ID: 4G9R RELATED DB: PDB
DBREF 4G9C A 432 726 UNP P15056 BRAF_HUMAN 432 726
DBREF 4G9C B 432 726 UNP P15056 BRAF_HUMAN 432 726
SEQADV 4G9C MET A 420 UNP P15056 EXPRESSION TAG
SEQADV 4G9C ASP A 421 UNP P15056 EXPRESSION TAG
SEQADV 4G9C ARG A 422 UNP P15056 EXPRESSION TAG
SEQADV 4G9C GLY A 423 UNP P15056 EXPRESSION TAG
SEQADV 4G9C SER A 424 UNP P15056 EXPRESSION TAG
SEQADV 4G9C HIS A 425 UNP P15056 EXPRESSION TAG
SEQADV 4G9C HIS A 426 UNP P15056 EXPRESSION TAG
SEQADV 4G9C HIS A 427 UNP P15056 EXPRESSION TAG
SEQADV 4G9C HIS A 428 UNP P15056 EXPRESSION TAG
SEQADV 4G9C HIS A 429 UNP P15056 EXPRESSION TAG
SEQADV 4G9C HIS A 430 UNP P15056 EXPRESSION TAG
SEQADV 4G9C GLY A 431 UNP P15056 EXPRESSION TAG
SEQADV 4G9C MET B 420 UNP P15056 EXPRESSION TAG
SEQADV 4G9C ASP B 421 UNP P15056 EXPRESSION TAG
SEQADV 4G9C ARG B 422 UNP P15056 EXPRESSION TAG
SEQADV 4G9C GLY B 423 UNP P15056 EXPRESSION TAG
SEQADV 4G9C SER B 424 UNP P15056 EXPRESSION TAG
SEQADV 4G9C HIS B 425 UNP P15056 EXPRESSION TAG
SEQADV 4G9C HIS B 426 UNP P15056 EXPRESSION TAG
SEQADV 4G9C HIS B 427 UNP P15056 EXPRESSION TAG
SEQADV 4G9C HIS B 428 UNP P15056 EXPRESSION TAG
SEQADV 4G9C HIS B 429 UNP P15056 EXPRESSION TAG
SEQADV 4G9C HIS B 430 UNP P15056 EXPRESSION TAG
SEQADV 4G9C GLY B 431 UNP P15056 EXPRESSION TAG
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 VAL 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 VAL 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 0WP A 801 36
HET 0WP B 801 36
HETNAM 0WP 3-{[3-(2-CYANOPROPAN-2-YL)BENZOYL]AMINO}-2,6-DIFLUORO-
HETNAM 2 0WP N-(3-METHOXY-2H-PYRAZOLO[3,4-B]PYRIDIN-5-YL)BENZAMIDE
FORMUL 3 0WP 2(C25 H20 F2 N6 O3)
HELIX 1 1 THR A 491 ARG A 506 1 16
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 MET A 627 1 7
HELIX 5 5 SER A 634 GLY A 652 1 19
HELIX 6 6 ASN A 661 GLY A 672 1 12
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 ALA A 718 1 13
HELIX 11 11 THR B 491 ARG B 506 1 16
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 ALA B 621 MET B 627 1 7
HELIX 15 15 SER B 634 GLY B 652 1 19
HELIX 16 16 ASN B 661 GLY B 672 1 12
HELIX 17 17 ASP B 677 VAL B 681 5 5
HELIX 18 18 PRO B 686 LEU B 697 1 12
HELIX 19 19 LYS B 700 ARG B 704 5 5
HELIX 20 20 LEU B 706 ALA B 718 1 13
SHEET 1 A 5 THR A 458 GLY A 464 0
SHEET 2 A 5 VAL A 471 LYS A 475 -1 O VAL A 471 N GLY A 464
SHEET 3 A 5 ASP A 479 MET A 484 -1 O VAL A 482 N TYR A 472
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 MET A 517 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 VAL A 590 ILE A 592 -1 O LYS A 591 N PHE A 583
SHEET 1 C 5 THR B 458 GLY B 464 0
SHEET 2 C 5 THR B 470 LYS B 475 -1 O VAL B 471 N GLY B 464
SHEET 3 C 5 ASP B 479 MET B 484 -1 O VAL B 482 N TYR B 472
SHEET 4 C 5 ALA B 526 GLN B 530 -1 O THR B 529 N ALA B 481
SHEET 5 C 5 PHE B 516 SER B 520 -1 N MET B 517 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 VAL B 590 ILE B 592 -1 O LYS B 591 N PHE B 583
SITE 1 AC1 18 ILE A 463 ALA A 481 LYS A 483 GLU A 501
SITE 2 AC1 18 VAL A 504 LEU A 505 ILE A 513 LEU A 514
SITE 3 AC1 18 ILE A 527 THR A 529 GLN A 530 TRP A 531
SITE 4 AC1 18 CYS A 532 ILE A 572 HIS A 574 PHE A 583
SITE 5 AC1 18 ASP A 594 PHE A 595
SITE 1 AC2 17 ILE B 463 ALA B 481 LYS B 483 GLU B 501
SITE 2 AC2 17 LEU B 505 LEU B 514 ILE B 527 THR B 529
SITE 3 AC2 17 GLN B 530 TRP B 531 CYS B 532 ILE B 573
SITE 4 AC2 17 HIS B 574 PHE B 583 GLY B 593 ASP B 594
SITE 5 AC2 17 PHE B 595
CRYST1 107.050 107.050 161.850 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 0.009341 0.000000 0.000000 0.00000
SCALE2 0.000000 0.009341 0.000000 0.00000
SCALE3 0.000000 0.000000 0.006179 0.00000
(ATOM LINES ARE NOT SHOWN.)
END
