HEADER TRANSFERASE/TRANSFERASE INHIBITOR 22-JUN-11 3SKC
TITLE HUMAN B-RAF KINASE IN COMPLEX WITH AN AMIDE LINKED 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: HUMAN B-RAF KINASE 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: HI5
KEYWDS KINASE, ATP-COMPETITIVE INHIBITOR, TRANSFERASE, RAS, MEK, C-RAF,
KEYWDS 2 TRANSFERASE-TRANSFERASE INHIBITOR COMPLEX
EXPDTA X-RAY DIFFRACTION
AUTHOR W.C.VOEGTLI,H.L.STURGIS
REVDAT 3 28-FEB-24 3SKC 1 REMARK SEQADV
REVDAT 2 14-DEC-11 3SKC 1 JRNL
REVDAT 1 17-AUG-11 3SKC 0
JRNL AUTH S.WENGLOWSKY,K.A.AHRENDT,A.J.BUCKMELTER,B.FENG,S.L.GLOOR,
JRNL AUTH 2 S.GRADL,J.GRINA,J.D.HANSEN,E.R.LAIRD,P.LUNGHOFER,S.MATHIEU,
JRNL AUTH 3 D.MORENO,B.NEWHOUSE,L.REN,T.RISOM,J.RUDOLPH,J.SEO,
JRNL AUTH 4 H.L.STURGIS,W.C.VOEGTLI,Z.WEN
JRNL TITL PYRAZOLOPYRIDINE INHIBITORS OF B-RAFV600E. PART 2:
JRNL TITL 2 STRUCTURE-ACTIVITY RELATIONSHIPS.
JRNL REF BIOORG.MED.CHEM.LETT. V. 21 5533 2011
JRNL REFN ISSN 0960-894X
JRNL PMID 21802293
JRNL DOI 10.1016/J.BMCL.2011.06.097
REMARK 2
REMARK 2 RESOLUTION. 3.20 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) : 3.20
REMARK 3 RESOLUTION RANGE LOW (ANGSTROMS) : 29.30
REMARK 3 DATA CUTOFF (SIGMA(F)) : 0.000
REMARK 3 DATA CUTOFF HIGH (ABS(F)) : 2139817.240
REMARK 3 DATA CUTOFF LOW (ABS(F)) : 0.0000
REMARK 3 COMPLETENESS (WORKING+TEST) (%) : 99.4
REMARK 3 NUMBER OF REFLECTIONS : 15245
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) : 0.235
REMARK 3 R VALUE (WORKING SET) : 0.233
REMARK 3 FREE R VALUE : 0.271
REMARK 3 FREE R VALUE TEST SET SIZE (%) : 5.900
REMARK 3 FREE R VALUE TEST SET COUNT : 905
REMARK 3 ESTIMATED ERROR OF FREE R VALUE : 0.009
REMARK 3
REMARK 3 FIT/AGREEMENT OF MODEL WITH ALL DATA.
REMARK 3 R VALUE (WORKING + TEST SET, NO CUTOFF) : 0.2390
REMARK 3 R VALUE (WORKING SET, NO CUTOFF) : 0.2360
REMARK 3 FREE R VALUE (NO CUTOFF) : 0.274
REMARK 3 FREE R VALUE TEST SET SIZE (%, NO CUTOFF) : 5.900
REMARK 3 FREE R VALUE TEST SET COUNT (NO CUTOFF) : 905
REMARK 3 ESTIMATED ERROR OF FREE R VALUE (NO CUTOFF) : 0.0090
REMARK 3 TOTAL NUMBER OF REFLECTIONS (NO CUTOFF) : 15245
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) : 3.20
REMARK 3 BIN RESOLUTION RANGE LOW (A) : 3.40
REMARK 3 BIN COMPLETENESS (WORKING+TEST) (%) : 98.90
REMARK 3 REFLECTIONS IN BIN (WORKING SET) : 2318
REMARK 3 BIN R VALUE (WORKING SET) : 0.3180
REMARK 3 BIN FREE R VALUE : 0.3910
REMARK 3 BIN FREE R VALUE TEST SET SIZE (%) : 5.80
REMARK 3 BIN FREE R VALUE TEST SET COUNT : 143
REMARK 3 ESTIMATED ERROR OF BIN FREE R VALUE : 0.033
REMARK 3
REMARK 3 NUMBER OF NON-HYDROGEN ATOMS USED IN REFINEMENT.
REMARK 3 PROTEIN ATOMS : 4291
REMARK 3 NUCLEIC ACID ATOMS : 0
REMARK 3 HETEROGEN ATOMS : 64
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) : 46.10
REMARK 3 OVERALL ANISOTROPIC B VALUE.
REMARK 3 B11 (A**2) : -3.24000
REMARK 3 B22 (A**2) : -3.24000
REMARK 3 B33 (A**2) : 6.49000
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) : 0.39
REMARK 3 ESD FROM SIGMAA (A) : 0.48
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) : 0.48
REMARK 3 ESD FROM C-V SIGMAA (A) : 0.53
REMARK 3
REMARK 3 RMS DEVIATIONS FROM IDEAL VALUES.
REMARK 3 BOND LENGTHS (A) : 0.010
REMARK 3 BOND ANGLES (DEGREES) : 1.200
REMARK 3 DIHEDRAL ANGLES (DEGREES) : 24.00
REMARK 3 IMPROPER ANGLES (DEGREES) : 0.670
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) : 1.470 ; 1.500
REMARK 3 MAIN-CHAIN ANGLE (A**2) : 2.680 ; 2.000
REMARK 3 SIDE-CHAIN BOND (A**2) : 1.550 ; 2.000
REMARK 3 SIDE-CHAIN ANGLE (A**2) : 2.650 ; 2.500
REMARK 3
REMARK 3 BULK SOLVENT MODELING.
REMARK 3 METHOD USED : FLAT MODEL
REMARK 3 KSOL : 0.33
REMARK 3 BSOL : 24.74
REMARK 3
REMARK 3 NCS MODEL : NONE
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 : AR00461060.PAR
REMARK 3 PARAMETER FILE 3 : WATER_REP.PARAM
REMARK 3 PARAMETER FILE 4 : NULL
REMARK 3 TOPOLOGY FILE 1 : PROTEIN.TOP
REMARK 3 TOPOLOGY FILE 2 : AR00461060.TOP
REMARK 3 TOPOLOGY FILE 3 : WATER.TOP
REMARK 3 TOPOLOGY FILE 4 : NULL
REMARK 3
REMARK 3 OTHER REFINEMENT REMARKS: BULK SOLVENT MODEL USED
REMARK 4
REMARK 4 3SKC COMPLIES WITH FORMAT V. 3.30, 13-JUL-11
REMARK 100
REMARK 100 THIS ENTRY HAS BEEN PROCESSED BY RCSB ON 29-JUN-11.
REMARK 100 THE DEPOSITION ID IS D_1000066308.
REMARK 200
REMARK 200 EXPERIMENTAL DETAILS
REMARK 200 EXPERIMENT TYPE : X-RAY DIFFRACTION
REMARK 200 DATE OF DATA COLLECTION : 06-AUG-08
REMARK 200 TEMPERATURE (KELVIN) : 100
REMARK 200 PH : 9.0
REMARK 200 NUMBER OF CRYSTALS USED : NULL
REMARK 200
REMARK 200 SYNCHROTRON (Y/N) : N
REMARK 200 RADIATION SOURCE : ROTATING ANODE
REMARK 200 BEAMLINE : NULL
REMARK 200 X-RAY GENERATOR MODEL : RIGAKU FR-E+ SUPERBRIGHT
REMARK 200 MONOCHROMATIC OR LAUE (M/L) : M
REMARK 200 WAVELENGTH OR RANGE (A) : 1.54
REMARK 200 MONOCHROMATOR : NULL
REMARK 200 OPTICS : OSMIC CONFOCAL
REMARK 200
REMARK 200 DETECTOR TYPE : IMAGE PLATE
REMARK 200 DETECTOR MANUFACTURER : RIGAKU RAXIS IV++
REMARK 200 INTENSITY-INTEGRATION SOFTWARE : MOSFLM
REMARK 200 DATA SCALING SOFTWARE : SCALA
REMARK 200
REMARK 200 NUMBER OF UNIQUE REFLECTIONS : 15245
REMARK 200 RESOLUTION RANGE HIGH (A) : 3.200
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 (%) : 99.4
REMARK 200 DATA REDUNDANCY : 3.800
REMARK 200 R MERGE (I) : 0.86000
REMARK 200 R SYM (I) : NULL
REMARK 200 <I/SIGMA(I)> FOR THE DATA SET : 8.3000
REMARK 200
REMARK 200 IN THE HIGHEST RESOLUTION SHELL.
REMARK 200 HIGHEST RESOLUTION SHELL, RANGE HIGH (A) : 3.20
REMARK 200 HIGHEST RESOLUTION SHELL, RANGE LOW (A) : 3.37
REMARK 200 COMPLETENESS FOR SHELL (%) : 99.2
REMARK 200 DATA REDUNDANCY IN SHELL : 3.90
REMARK 200 R MERGE FOR SHELL (I) : 0.33100
REMARK 200 R SYM FOR SHELL (I) : NULL
REMARK 200 <I/SIGMA(I)> FOR SHELL : 2.300
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 (%): 60.70
REMARK 280 MATTHEWS COEFFICIENT, VM (ANGSTROMS**3/DA): 3.13
REMARK 280
REMARK 280 CRYSTALLIZATION CONDITIONS: PEG 10000, 100 MM TRIS PH 9.0, 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 75.73500
REMARK 290 SMTRY1 3 0.000000 -1.000000 0.000000 53.95000
REMARK 290 SMTRY2 3 1.000000 0.000000 0.000000 53.95000
REMARK 290 SMTRY3 3 0.000000 0.000000 1.000000 37.86750
REMARK 290 SMTRY1 4 0.000000 1.000000 0.000000 53.95000
REMARK 290 SMTRY2 4 -1.000000 0.000000 0.000000 53.95000
REMARK 290 SMTRY3 4 0.000000 0.000000 1.000000 113.60250
REMARK 290 SMTRY1 5 -1.000000 0.000000 0.000000 53.95000
REMARK 290 SMTRY2 5 0.000000 1.000000 0.000000 53.95000
REMARK 290 SMTRY3 5 0.000000 0.000000 -1.000000 37.86750
REMARK 290 SMTRY1 6 1.000000 0.000000 0.000000 53.95000
REMARK 290 SMTRY2 6 0.000000 -1.000000 0.000000 53.95000
REMARK 290 SMTRY3 6 0.000000 0.000000 -1.000000 113.60250
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 75.73500
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 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 LEU A 597
REMARK 465 ALA A 598
REMARK 465 THR A 599
REMARK 465 VAL A 600
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 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 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
REMARK 500
REMARK 500 THE FOLLOWING ATOMS THAT ARE RELATED BY CRYSTALLOGRAPHIC
REMARK 500 SYMMETRY ARE IN CLOSE CONTACT. AN ATOM LOCATED WITHIN 0.15
REMARK 500 ANGSTROMS OF A SYMMETRY RELATED ATOM IS ASSUMED TO BE ON A
REMARK 500 SPECIAL POSITION AND IS, THEREFORE, LISTED IN REMARK 375
REMARK 500 INSTEAD OF REMARK 500. ATOMS WITH NON-BLANK ALTERNATE
REMARK 500 LOCATION INDICATORS ARE NOT INCLUDED IN THE CALCULATIONS.
REMARK 500
REMARK 500 DISTANCE CUTOFF:
REMARK 500 2.2 ANGSTROMS FOR CONTACTS NOT INVOLVING HYDROGEN ATOMS
REMARK 500 1.6 ANGSTROMS FOR CONTACTS INVOLVING HYDROGEN ATOMS
REMARK 500
REMARK 500 ATM1 RES C SSEQI ATM2 RES C SSEQI SSYMOP DISTANCE
REMARK 500 NH2 ARG B 662 NH2 ARG B 662 7645 2.17
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 449 145.36 -34.26
REMARK 500 ASP A 454 153.98 -46.36
REMARK 500 ILE A 463 -45.24 -135.57
REMARK 500 SER A 465 -167.47 -109.88
REMARK 500 PHE A 468 7.27 40.83
REMARK 500 ASN A 486 65.31 27.74
REMARK 500 THR A 488 51.39 36.92
REMARK 500 ALA A 489 99.69 63.01
REMARK 500 THR A 491 40.70 90.48
REMARK 500 GLN A 493 66.41 -101.36
REMARK 500 ARG A 509 88.96 -151.96
REMARK 500 LYS A 522 -86.18 -54.85
REMARK 500 GLN A 530 150.99 -44.59
REMARK 500 ASP A 576 41.25 -161.15
REMARK 500 LYS A 578 166.62 172.84
REMARK 500 ASP A 587 16.94 52.95
REMARK 500 ASP A 594 74.85 94.82
REMARK 500 PHE A 595 -134.09 -82.48
REMARK 500 SER A 614 -26.66 -166.13
REMARK 500 SER A 616 40.44 -157.77
REMARK 500 MET A 627 86.94 -50.62
REMARK 500 ASP B 449 146.10 -36.24
REMARK 500 ASP B 454 152.02 -46.32
REMARK 500 ILE B 463 -45.99 -134.59
REMARK 500 SER B 467 -63.93 -90.32
REMARK 500 ASN B 486 64.19 26.14
REMARK 500 THR B 488 49.66 37.70
REMARK 500 ALA B 489 100.75 63.81
REMARK 500 THR B 491 41.90 90.01
REMARK 500 GLN B 493 66.48 -101.14
REMARK 500 LYS B 522 -84.51 -56.20
REMARK 500 GLN B 530 151.23 -46.79
REMARK 500 ASP B 576 41.90 -163.68
REMARK 500 LYS B 578 165.70 172.40
REMARK 500 GLU B 586 32.23 39.73
REMARK 500 ASP B 587 15.33 53.73
REMARK 500 ASP B 594 39.50 86.44
REMARK 500 LYS B 601 -57.13 -163.72
REMARK 500 SER B 602 17.33 -66.98
REMARK 500 ARG B 603 -6.14 -150.80
REMARK 500 LEU B 613 49.48 -63.29
REMARK 500 SER B 614 -26.01 -168.63
REMARK 500 SER B 616 39.42 -156.00
REMARK 500 MET B 627 85.42 -48.96
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 GLN A 493 GLN A 494 149.80
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 BR2 A 801
REMARK 800
REMARK 800 SITE_IDENTIFIER: AC2
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: BINDING SITE FOR RESIDUE BR2 B 801
DBREF 3SKC A 432 726 UNP P15056 BRAF_HUMAN 432 726
DBREF 3SKC B 432 726 UNP P15056 BRAF_HUMAN 432 726
SEQADV 3SKC MET A 420 UNP P15056 EXPRESSION TAG
SEQADV 3SKC ASP A 421 UNP P15056 EXPRESSION TAG
SEQADV 3SKC ARG A 422 UNP P15056 EXPRESSION TAG
SEQADV 3SKC GLY A 423 UNP P15056 EXPRESSION TAG
SEQADV 3SKC SER A 424 UNP P15056 EXPRESSION TAG
SEQADV 3SKC HIS A 425 UNP P15056 EXPRESSION TAG
SEQADV 3SKC HIS A 426 UNP P15056 EXPRESSION TAG
SEQADV 3SKC HIS A 427 UNP P15056 EXPRESSION TAG
SEQADV 3SKC HIS A 428 UNP P15056 EXPRESSION TAG
SEQADV 3SKC HIS A 429 UNP P15056 EXPRESSION TAG
SEQADV 3SKC HIS A 430 UNP P15056 EXPRESSION TAG
SEQADV 3SKC GLY A 431 UNP P15056 EXPRESSION TAG
SEQADV 3SKC MET B 420 UNP P15056 EXPRESSION TAG
SEQADV 3SKC ASP B 421 UNP P15056 EXPRESSION TAG
SEQADV 3SKC ARG B 422 UNP P15056 EXPRESSION TAG
SEQADV 3SKC GLY B 423 UNP P15056 EXPRESSION TAG
SEQADV 3SKC SER B 424 UNP P15056 EXPRESSION TAG
SEQADV 3SKC HIS B 425 UNP P15056 EXPRESSION TAG
SEQADV 3SKC HIS B 426 UNP P15056 EXPRESSION TAG
SEQADV 3SKC HIS B 427 UNP P15056 EXPRESSION TAG
SEQADV 3SKC HIS B 428 UNP P15056 EXPRESSION TAG
SEQADV 3SKC HIS B 429 UNP P15056 EXPRESSION TAG
SEQADV 3SKC HIS B 430 UNP P15056 EXPRESSION TAG
SEQADV 3SKC 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 BR2 A 801 32
HET BR2 B 801 32
HETNAM BR2 2,6-DIFLUORO-N-[(5S)-3-METHOXY-5H-PYRAZOLO[3,4-
HETNAM 2 BR2 B]PYRIDIN-5-YL]-3-[(PHENYLSULFONYL)AMINO]BENZAMIDE
FORMUL 3 BR2 2(C20 H15 F2 N5 O4 S)
HELIX 1 1 GLN A 494 ARG A 506 1 13
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 LYS A 578 ASN A 580 5 3
HELIX 5 5 SER A 616 MET A 620 5 5
HELIX 6 6 ALA A 621 ARG A 626 1 6
HELIX 7 7 SER A 634 GLY A 652 1 19
HELIX 8 8 ASN A 661 ARG A 671 1 11
HELIX 9 9 ASP A 677 VAL A 681 5 5
HELIX 10 10 PRO A 686 LEU A 697 1 12
HELIX 11 11 LYS A 700 ARG A 704 5 5
HELIX 12 12 LEU A 706 SER A 720 1 15
HELIX 13 13 GLN B 494 ARG B 506 1 13
HELIX 14 14 LEU B 537 ILE B 543 1 7
HELIX 15 15 GLU B 549 LYS B 570 1 22
HELIX 16 16 LYS B 578 ASN B 580 5 3
HELIX 17 17 SER B 607 LEU B 613 1 7
HELIX 18 18 SER B 616 MET B 620 5 5
HELIX 19 19 ALA B 621 ARG B 626 1 6
HELIX 20 20 SER B 634 GLY B 652 1 19
HELIX 21 21 ASN B 661 ARG B 671 1 11
HELIX 22 22 ASP B 677 VAL B 681 5 5
HELIX 23 23 PRO B 686 LEU B 697 1 12
HELIX 24 24 LYS B 700 ARG B 704 5 5
HELIX 25 25 LEU B 706 SER B 720 1 15
SHEET 1 A 5 THR A 458 ARG A 462 0
SHEET 2 A 5 THR A 470 LYS A 475 -1 O LYS A 473 N GLN A 461
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 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 LYS A 591 N PHE A 583
SHEET 1 C 5 THR B 458 ARG B 462 0
SHEET 2 C 5 THR B 470 LYS B 475 -1 O LYS B 473 N GLN B 461
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 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 5.53
CISPEP 2 PRO A 492 GLN A 493 0 -8.21
CISPEP 3 PRO B 490 THR B 491 0 5.48
CISPEP 4 PRO B 492 GLN B 493 0 -7.97
SITE 1 AC1 12 ALA A 481 LYS A 483 LEU A 505 LEU A 514
SITE 2 AC1 12 PHE A 516 ILE A 527 THR A 529 GLN A 530
SITE 3 AC1 12 TRP A 531 CYS A 532 ASP A 594 PHE A 595
SITE 1 AC2 12 ALA B 481 LYS B 483 LEU B 505 LEU B 514
SITE 2 AC2 12 THR B 529 GLN B 530 TRP B 531 CYS B 532
SITE 3 AC2 12 PHE B 583 ASP B 594 PHE B 595 GLY B 596
CRYST1 107.900 107.900 151.470 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 0.009268 0.000000 0.000000 0.00000
SCALE2 0.000000 0.009268 0.000000 0.00000
SCALE3 0.000000 0.000000 0.006602 0.00000
(ATOM LINES ARE NOT SHOWN.)
END
