HEADER TRANSFERASE 08-APR-11 2YFX
TITLE STRUCTURE OF L1196M MUTANT ANAPLASTIC LYMPHOMA KINASE IN COMPLEX WITH
TITLE 2 CRIZOTINIB
COMPND MOL_ID: 1;
COMPND 2 MOLECULE: TYROSINE-PROTEIN KINASE RECEPTOR;
COMPND 3 CHAIN: A;
COMPND 4 FRAGMENT: KINASE DOMAIN, RESIDUES 105-423;
COMPND 5 SYNONYM: ANAPLASTIC LYMPHOMA KINASE;
COMPND 6 EC: 2.7.10.1;
COMPND 7 ENGINEERED: YES;
COMPND 8 MUTATION: YES
SOURCE MOL_ID: 1;
SOURCE 2 ORGANISM_SCIENTIFIC: HOMO SAPIENS;
SOURCE 3 ORGANISM_COMMON: HUMAN;
SOURCE 4 ORGANISM_TAXID: 9606;
SOURCE 5 EXPRESSION_SYSTEM: SPODOPTERA FRUGIPERDA;
SOURCE 6 EXPRESSION_SYSTEM_COMMON: FALL ARMYWORM;
SOURCE 7 EXPRESSION_SYSTEM_TAXID: 7108;
SOURCE 8 EXPRESSION_SYSTEM_CELL_LINE: SF9;
SOURCE 9 EXPRESSION_SYSTEM_VECTOR_TYPE: BACULOVIRUS;
SOURCE 10 EXPRESSION_SYSTEM_PLASMID: PFASTBAC
KEYWDS NUCLEOTIDE-BINDING, TRANSFERASE, RECEPTOR
EXPDTA X-RAY DIFFRACTION
AUTHOR M.MCTIGUE,Y.DENG,W.LIU,A.BROOUN
REVDAT 4 20-DEC-23 2YFX 1 REMARK
REVDAT 3 08-MAY-19 2YFX 1 REMARK
REVDAT 2 19-MAR-14 2YFX 1 JRNL REMARK VERSN
REVDAT 1 04-MAY-11 2YFX 0
JRNL AUTH Q.HUANG,T.W.JOHNSON,S.BAILEY,A.BROOUN,K.D.BUNKER,B.J.BURKE,
JRNL AUTH 2 M.R.COLLINS,A.S.COOK,J.J.CUI,K.N.DACK,J.G.DEAL,Y.DENG,
JRNL AUTH 3 D.DINH,L.D.ENGSTROM,M.HE,J.HOFFMAN,R.L.HOFFMAN,P.S.JOHNSON,
JRNL AUTH 4 R.S.KANIA,H.LAM,J.L.LAM,P.T.LE,Q.LI,L.LINGARDO,W.LIU,M.W.LU,
JRNL AUTH 5 M.MCTIGUE,C.L.PALMER,P.F.RICHARDSON,N.W.SACH,H.SHEN,T.SMEAL,
JRNL AUTH 6 G.L.SMITH,A.E.STEWART,S.TIMOFEEVSKI,K.TSAPARIKOS,H.WANG,
JRNL AUTH 7 H.ZHU,J.ZHU,H.Y.ZOU,M.P.EDWARDS
JRNL TITL DESIGN OF POTENT AND SELECTIVE INHIBITORS TO OVERCOME
JRNL TITL 2 CLINICAL ANAPLASTIC LYMPHOMA KINASE MUTATIONS RESISTANT TO
JRNL TITL 3 CRIZOTINIB.
JRNL REF J.MED.CHEM. V. 57 1170 2014
JRNL REFN ISSN 0022-2623
JRNL PMID 24432909
JRNL DOI 10.1021/JM401805H
REMARK 2
REMARK 2 RESOLUTION. 1.70 ANGSTROMS.
REMARK 3
REMARK 3 REFINEMENT.
REMARK 3 PROGRAM : CNS 2005
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 : NULL
REMARK 3
REMARK 3 DATA USED IN REFINEMENT.
REMARK 3 RESOLUTION RANGE HIGH (ANGSTROMS) : 1.70
REMARK 3 RESOLUTION RANGE LOW (ANGSTROMS) : 36.04
REMARK 3 DATA CUTOFF (SIGMA(F)) : 0.000
REMARK 3 DATA CUTOFF HIGH (ABS(F)) : 1136270.830
REMARK 3 DATA CUTOFF LOW (ABS(F)) : 0.0000
REMARK 3 COMPLETENESS (WORKING+TEST) (%) : 99.1
REMARK 3 NUMBER OF REFLECTIONS : 34791
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 SET) : 0.208
REMARK 3 FREE R VALUE : 0.234
REMARK 3 FREE R VALUE TEST SET SIZE (%) : 5.000
REMARK 3 FREE R VALUE TEST SET COUNT : 1744
REMARK 3 ESTIMATED ERROR OF FREE R VALUE : 0.006
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) : 1.70
REMARK 3 BIN RESOLUTION RANGE LOW (A) : 1.81
REMARK 3 BIN COMPLETENESS (WORKING+TEST) (%) : 99.90
REMARK 3 REFLECTIONS IN BIN (WORKING SET) : 5425
REMARK 3 BIN R VALUE (WORKING SET) : 0.2360
REMARK 3 BIN FREE R VALUE : 0.2660
REMARK 3 BIN FREE R VALUE TEST SET SIZE (%) : 5.60
REMARK 3 BIN FREE R VALUE TEST SET COUNT : 321
REMARK 3 ESTIMATED ERROR OF BIN FREE R VALUE : 0.015
REMARK 3
REMARK 3 NUMBER OF NON-HYDROGEN ATOMS USED IN REFINEMENT.
REMARK 3 PROTEIN ATOMS : 2300
REMARK 3 NUCLEIC ACID ATOMS : 0
REMARK 3 HETEROGEN ATOMS : 30
REMARK 3 SOLVENT ATOMS : 237
REMARK 3
REMARK 3 B VALUES.
REMARK 3 FROM WILSON PLOT (A**2) : 23.30
REMARK 3 MEAN B VALUE (OVERALL, A**2) : 28.20
REMARK 3 OVERALL ANISOTROPIC B VALUE.
REMARK 3 B11 (A**2) : -0.80000
REMARK 3 B22 (A**2) : -3.78000
REMARK 3 B33 (A**2) : 4.57000
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) : 0.19
REMARK 3 ESD FROM SIGMAA (A) : 0.11
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) : 0.23
REMARK 3 ESD FROM C-V SIGMAA (A) : 0.14
REMARK 3
REMARK 3 RMS DEVIATIONS FROM IDEAL VALUES.
REMARK 3 BOND LENGTHS (A) : 0.004
REMARK 3 BOND ANGLES (DEGREES) : 0.800
REMARK 3 DIHEDRAL ANGLES (DEGREES) : 18.80
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) : 1.380 ; 1.500
REMARK 3 MAIN-CHAIN ANGLE (A**2) : 2.210 ; 2.000
REMARK 3 SIDE-CHAIN BOND (A**2) : 2.380 ; 2.000
REMARK 3 SIDE-CHAIN ANGLE (A**2) : 3.580 ; 2.500
REMARK 3
REMARK 3 BULK SOLVENT MODELING.
REMARK 3 METHOD USED : FLAT MODEL
REMARK 3 KSOL : 0.39
REMARK 3 BSOL : 50.78
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.PARAM
REMARK 3 PARAMETER FILE 2 : DNA-RNA_REP.PARAM
REMARK 3 PARAMETER FILE 3 : WATER_REP.PARAM
REMARK 3 PARAMETER FILE 4 : ION.PARAM
REMARK 3 PARAMETER FILE 5 : UNL.PARAM
REMARK 3 PARAMETER FILE 6 : NULL
REMARK 3 TOPOLOGY FILE 1 : PROTEIN.TOP
REMARK 3 TOPOLOGY FILE 2 : DNA-RNA.TOP
REMARK 3 TOPOLOGY FILE 3 : WATER.TOP
REMARK 3 TOPOLOGY FILE 4 : ION.TOP
REMARK 3 TOPOLOGY FILE 5 : UNL.TOP
REMARK 3 TOPOLOGY FILE 6 : NULL
REMARK 3
REMARK 3 OTHER REFINEMENT REMARKS: NULL
REMARK 4
REMARK 4 2YFX COMPLIES WITH FORMAT V. 3.30, 13-JUL-11
REMARK 100
REMARK 100 THIS ENTRY HAS BEEN PROCESSED BY PDBE ON 08-APR-11.
REMARK 100 THE DEPOSITION ID IS D_1290047977.
REMARK 200
REMARK 200 EXPERIMENTAL DETAILS
REMARK 200 EXPERIMENT TYPE : X-RAY DIFFRACTION
REMARK 200 DATE OF DATA COLLECTION : 12-APR-10
REMARK 200 TEMPERATURE (KELVIN) : 98
REMARK 200 PH : 5.6
REMARK 200 NUMBER OF CRYSTALS USED : 1
REMARK 200
REMARK 200 SYNCHROTRON (Y/N) : Y
REMARK 200 RADIATION SOURCE : APS
REMARK 200 BEAMLINE : 17-ID
REMARK 200 X-RAY GENERATOR MODEL : NULL
REMARK 200 MONOCHROMATIC OR LAUE (M/L) : M
REMARK 200 WAVELENGTH OR RANGE (A) : 1.0
REMARK 200 MONOCHROMATOR : NULL
REMARK 200 OPTICS : NULL
REMARK 200
REMARK 200 DETECTOR TYPE : PIXEL
REMARK 200 DETECTOR MANUFACTURER : DECTRIS PILATUS 6M
REMARK 200 INTENSITY-INTEGRATION SOFTWARE : XDS
REMARK 200 DATA SCALING SOFTWARE : SCALA
REMARK 200
REMARK 200 NUMBER OF UNIQUE REFLECTIONS : 43152
REMARK 200 RESOLUTION RANGE HIGH (A) : 1.570
REMARK 200 RESOLUTION RANGE LOW (A) : 105.250
REMARK 200 REJECTION CRITERIA (SIGMA(I)) : 1.000
REMARK 200
REMARK 200 OVERALL.
REMARK 200 COMPLETENESS FOR RANGE (%) : 98.2
REMARK 200 DATA REDUNDANCY : 6.200
REMARK 200 R MERGE (I) : 0.05000
REMARK 200 R SYM (I) : NULL
REMARK 200 <I/SIGMA(I)> FOR THE DATA SET : 18.3000
REMARK 200
REMARK 200 IN THE HIGHEST RESOLUTION SHELL.
REMARK 200 HIGHEST RESOLUTION SHELL, RANGE HIGH (A) : 1.57
REMARK 200 HIGHEST RESOLUTION SHELL, RANGE LOW (A) : 1.66
REMARK 200 COMPLETENESS FOR SHELL (%) : 91.5
REMARK 200 DATA REDUNDANCY IN SHELL : 2.20
REMARK 200 R MERGE FOR SHELL (I) : 0.34000
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: CNX
REMARK 200 STARTING MODEL: PDB ENTRY 2XP2
REMARK 200
REMARK 200 REMARK: NONE
REMARK 280
REMARK 280 CRYSTAL
REMARK 280 SOLVENT CONTENT, VS (%): 44.60
REMARK 280 MATTHEWS COEFFICIENT, VM (ANGSTROMS**3/DA): 2.20
REMARK 280
REMARK 280 CRYSTALLIZATION CONDITIONS: HANGING DROP VAPOR DIFFUSION AT 13
REMARK 280 DEGREES C. EQUAL VOLUMES OF PURIFIED PROTEIN SOLUTION
REMARK 280 (APPROXIMATELY 7 MG/ML)CONTAINING 0.8 MM CRIZOTINIB WERE
REMARK 280 COMBINED WITH A SOLUTION CONTAINING: 0.15 M AMMONIUM SULFATE, 10%
REMARK 280 MONOMETHYLETHER PEG5K AND 0.1M MES PH 5.6., VAPOR DIFFUSION,
REMARK 280 HANGING DROP, TEMPERATURE 286K
REMARK 290
REMARK 290 CRYSTALLOGRAPHIC SYMMETRY
REMARK 290 SYMMETRY OPERATORS FOR SPACE GROUP: P 21 21 21
REMARK 290
REMARK 290 SYMOP SYMMETRY
REMARK 290 NNNMMM OPERATOR
REMARK 290 1555 X,Y,Z
REMARK 290 2555 -X+1/2,-Y,Z+1/2
REMARK 290 3555 -X,Y+1/2,-Z+1/2
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 25.86050
REMARK 290 SMTRY2 2 0.000000 -1.000000 0.000000 0.00000
REMARK 290 SMTRY3 2 0.000000 0.000000 1.000000 52.62650
REMARK 290 SMTRY1 3 -1.000000 0.000000 0.000000 0.00000
REMARK 290 SMTRY2 3 0.000000 1.000000 0.000000 28.58700
REMARK 290 SMTRY3 3 0.000000 0.000000 -1.000000 52.62650
REMARK 290 SMTRY1 4 1.000000 0.000000 0.000000 25.86050
REMARK 290 SMTRY2 4 0.000000 -1.000000 0.000000 28.58700
REMARK 290 SMTRY3 4 0.000000 0.000000 -1.000000 0.00000
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: 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 400
REMARK 400 COMPOUND
REMARK 400 ENGINEERED RESIDUE IN CHAIN A, LEU 208 TO MET
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 1085
REMARK 465 ALA A 1086
REMARK 465 HIS A 1087
REMARK 465 HIS A 1088
REMARK 465 HIS A 1089
REMARK 465 HIS A 1090
REMARK 465 HIS A 1091
REMARK 465 HIS A 1092
REMARK 465 GLY A 1123
REMARK 465 HIS A 1124
REMARK 465 SER A 1136
REMARK 465 GLY A 1137
REMARK 465 MET A 1138
REMARK 465 PRO A 1139
REMARK 465 ASN A 1140
REMARK 465 ASP A 1141
REMARK 465 PRO A 1142
REMARK 465 SER A 1143
REMARK 465 ALA A 1280
REMARK 465 SER A 1281
REMARK 465 TYR A 1282
REMARK 465 TYR A 1283
REMARK 465 ARG A 1284
REMARK 465 LYS A 1285
REMARK 465 GLY A 1402
REMARK 465 PRO A 1403
REMARK 465 LEU A 1404
REMARK 465 VAL A 1405
REMARK 465 GLU A 1406
REMARK 465 GLU A 1407
REMARK 465 GLU A 1408
REMARK 465 GLU A 1409
REMARK 465 LYS A 1410
REMARK 465 VAL A 1411
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 TYR A1401 CA C O CB CG CD1 CD2
REMARK 470 TYR A1401 CE1 CE2 CZ OH
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 ALA A1126 -157.71 -68.86
REMARK 500 ARG A1248 -9.23 78.32
REMARK 500 ASP A1249 52.70 -150.31
REMARK 500 GLU A1400 76.96 -56.41
REMARK 500
REMARK 500 REMARK: NULL
REMARK 525
REMARK 525 SOLVENT
REMARK 525
REMARK 525 THE SOLVENT MOLECULES HAVE CHAIN IDENTIFIERS THAT
REMARK 525 INDICATE THE POLYMER CHAIN WITH WHICH THEY ARE MOST
REMARK 525 CLOSELY ASSOCIATED. THE REMARK LISTS ALL THE SOLVENT
REMARK 525 MOLECULES WHICH ARE MORE THAN 5A AWAY FROM THE
REMARK 525 NEAREST POLYMER CHAIN (M = MODEL NUMBER;
REMARK 525 RES=RESIDUE NAME; C=CHAIN IDENTIFIER; SSEQ=SEQUENCE
REMARK 525 NUMBER; I=INSERTION CODE):
REMARK 525
REMARK 525 M RES CSSEQI
REMARK 525 HOH A2030 DISTANCE = 5.83 ANGSTROMS
REMARK 800
REMARK 800 SITE
REMARK 800 SITE_IDENTIFIER: AC1
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: BINDING SITE FOR RESIDUE VGH A 9000
REMARK 900
REMARK 900 RELATED ENTRIES
REMARK 900 RELATED ID: 2XP2 RELATED DB: PDB
REMARK 900 STRUCTURE OF THE HUMAN ANAPLASTIC LYMPHOMA KINASE IN COMPLEX WITH
REMARK 900 CRIZOTINIB (PF-02341066)
REMARK 900 RELATED ID: 2YHV RELATED DB: PDB
REMARK 900 STRUCTURE OF L1196M MUTANT ANAPLASTIC LYMPHOMA KINASE
REMARK 900 RELATED ID: 4ANL RELATED DB: PDB
REMARK 900 STRUCTURE OF G1269A MUTANT ANAPLASTIC LYMPHOMA KINASE
REMARK 900 RELATED ID: 4ANQ RELATED DB: PDB
REMARK 900 STRUCTURE OF G1269A MUTANT ANAPLASTIC LYMPHOMA KINASE IN COMPLEX
REMARK 900 WITH CRIZOTINIB
REMARK 900 RELATED ID: 4CCB RELATED DB: PDB
REMARK 900 STRUCTURE OF THE HUMAN ANAPLASTIC LYMPHOMA KINASE IN COMPLEX WITH 3-
REMARK 900 ((R)-1-(5-FLUORO-2-(2H-1,2,3- TRIAZOL-2-YL)PHENYL)ETHOXY)-5-(5-
REMARK 900 METHYL-1H-PYRAZOL- 4-YL)PYRIDIN-2-AMINE
REMARK 900 RELATED ID: 4CCU RELATED DB: PDB
REMARK 900 STRUCTURE OF THE HUMAN ANAPLASTIC LYMPHOMA KINASE IN COMPLEX WITH 2-
REMARK 900 (5-(6-AMINO-5-((R)-1-(5-FLUORO-2 -(2H-1,2,3-TRIAZOL-2-YL)PHENYL)
REMARK 900 ETHOXY)PYRIDIN-3- YL)-4-METHYLTHIAZOL-2-YL)PROPAN-2-OL
REMARK 900 RELATED ID: 4CD0 RELATED DB: PDB
REMARK 900 STRUCTURE OF L1196M MUTANT HUMAN ANAPLASTIC LYMPHOMA KINASE IN
REMARK 900 COMPLEX WITH 2-(5-(6-AMINO-5-((R)-1-(5 -FLUORO-2-(2H-1,2,3-TRIAZOL-
REMARK 900 2-YL)PHENYL)ETHOXY) PYRIDIN-3-YL)-4-METHYLTHIAZOL-2-YL)PROPANE-1,2-
REMARK 900 DIOL
DBREF 2YFX A 1093 1411 UNP B6EXY4 B6EXY4_HUMAN 105 423
SEQADV 2YFX MET A 1085 UNP B6EXY4 EXPRESSION TAG
SEQADV 2YFX ALA A 1086 UNP B6EXY4 EXPRESSION TAG
SEQADV 2YFX HIS A 1087 UNP B6EXY4 EXPRESSION TAG
SEQADV 2YFX HIS A 1088 UNP B6EXY4 EXPRESSION TAG
SEQADV 2YFX HIS A 1089 UNP B6EXY4 EXPRESSION TAG
SEQADV 2YFX HIS A 1090 UNP B6EXY4 EXPRESSION TAG
SEQADV 2YFX HIS A 1091 UNP B6EXY4 EXPRESSION TAG
SEQADV 2YFX HIS A 1092 UNP B6EXY4 EXPRESSION TAG
SEQADV 2YFX MET A 1196 UNP B6EXY4 LEU 208 ENGINEERED MUTATION
SEQRES 1 A 327 MET ALA HIS HIS HIS HIS HIS HIS ASN PRO ASN TYR CYS
SEQRES 2 A 327 PHE ALA GLY LYS THR SER SER ILE SER ASP LEU LYS GLU
SEQRES 3 A 327 VAL PRO ARG LYS ASN ILE THR LEU ILE ARG GLY LEU GLY
SEQRES 4 A 327 HIS GLY ALA PHE GLY GLU VAL TYR GLU GLY GLN VAL SER
SEQRES 5 A 327 GLY MET PRO ASN ASP PRO SER PRO LEU GLN VAL ALA VAL
SEQRES 6 A 327 LYS THR LEU PRO GLU VAL CYS SER GLU GLN ASP GLU LEU
SEQRES 7 A 327 ASP PHE LEU MET GLU ALA LEU ILE ILE SER LYS PHE ASN
SEQRES 8 A 327 HIS GLN ASN ILE VAL ARG CYS ILE GLY VAL SER LEU GLN
SEQRES 9 A 327 SER LEU PRO ARG PHE ILE LEU MET GLU LEU MET ALA GLY
SEQRES 10 A 327 GLY ASP LEU LYS SER PHE LEU ARG GLU THR ARG PRO ARG
SEQRES 11 A 327 PRO SER GLN PRO SER SER LEU ALA MET LEU ASP LEU LEU
SEQRES 12 A 327 HIS VAL ALA ARG ASP ILE ALA CYS GLY CYS GLN TYR LEU
SEQRES 13 A 327 GLU GLU ASN HIS PHE ILE HIS ARG ASP ILE ALA ALA ARG
SEQRES 14 A 327 ASN CYS LEU LEU THR CYS PRO GLY PRO GLY ARG VAL ALA
SEQRES 15 A 327 LYS ILE GLY ASP PHE GLY MET ALA ARG ASP ILE TYR ARG
SEQRES 16 A 327 ALA SER TYR TYR ARG LYS GLY GLY CYS ALA MET LEU PRO
SEQRES 17 A 327 VAL LYS TRP MET PRO PRO GLU ALA PHE MET GLU GLY ILE
SEQRES 18 A 327 PHE THR SER LYS THR ASP THR TRP SER PHE GLY VAL LEU
SEQRES 19 A 327 LEU TRP GLU ILE PHE SER LEU GLY TYR MET PRO TYR PRO
SEQRES 20 A 327 SER LYS SER ASN GLN GLU VAL LEU GLU PHE VAL THR SER
SEQRES 21 A 327 GLY GLY ARG MET ASP PRO PRO LYS ASN CYS PRO GLY PRO
SEQRES 22 A 327 VAL TYR ARG ILE MET THR GLN CYS TRP GLN HIS GLN PRO
SEQRES 23 A 327 GLU ASP ARG PRO ASN PHE ALA ILE ILE LEU GLU ARG ILE
SEQRES 24 A 327 GLU TYR CYS THR GLN ASP PRO ASP VAL ILE ASN THR ALA
SEQRES 25 A 327 LEU PRO ILE GLU TYR GLY PRO LEU VAL GLU GLU GLU GLU
SEQRES 26 A 327 LYS VAL
HET VGH A9000 30
HETNAM VGH 3-[(1R)-1-(2,6-DICHLORO-3-FLUOROPHENYL)ETHOXY]-5-(1-
HETNAM 2 VGH PIPERIDIN-4-YL-1H-PYRAZOL-4-YL)PYRIDIN-2-AMINE
HETSYN VGH CRIZOTINIB
FORMUL 2 VGH C21 H22 CL2 F N5 O
FORMUL 3 HOH *237(H2 O)
HELIX 1 1 SER A 1104 LEU A 1108 5 5
HELIX 2 2 PRO A 1112 ILE A 1116 5 5
HELIX 3 3 SER A 1157 PHE A 1174 1 18
HELIX 4 4 LEU A 1204 THR A 1211 1 8
HELIX 5 5 ALA A 1222 ASN A 1243 1 22
HELIX 6 6 ALA A 1251 ARG A 1253 5 3
HELIX 7 7 PHE A 1271 ARG A 1279 1 9
HELIX 8 8 GLY A 1287 LEU A 1291 5 5
HELIX 9 9 PRO A 1292 MET A 1296 5 5
HELIX 10 10 PRO A 1297 GLY A 1304 1 8
HELIX 11 11 THR A 1307 SER A 1324 1 18
HELIX 12 12 SER A 1334 SER A 1344 1 11
HELIX 13 13 PRO A 1355 TRP A 1366 1 12
HELIX 14 14 GLN A 1369 ARG A 1373 5 5
HELIX 15 15 ASN A 1375 ASP A 1389 1 15
HELIX 16 16 ASP A 1389 ASN A 1394 1 6
SHEET 1 AA 2 TYR A1096 PHE A1098 0
SHEET 2 AA 2 LYS A1101 SER A1103 -1 O LYS A1101 N PHE A1098
SHEET 1 AB 5 THR A1117 GLY A1121 0
SHEET 2 AB 5 VAL A1130 GLN A1134 -1 O GLU A1132 N ILE A1119
SHEET 3 AB 5 GLN A1146 THR A1151 -1 O VAL A1147 N GLY A1133
SHEET 4 AB 5 PHE A1193 GLU A1197 -1 O ILE A1194 N LYS A1150
SHEET 5 AB 5 CYS A1182 SER A1186 -1 N ILE A1183 O LEU A1195
SHEET 1 AC 3 GLY A1202 ASP A1203 0
SHEET 2 AC 3 CYS A1255 LEU A1257 -1 N LEU A1257 O GLY A1202
SHEET 3 AC 3 ALA A1266 ILE A1268 -1 O LYS A1267 N LEU A1256
CISPEP 1 LEU A 1190 PRO A 1191 0 -3.97
SITE 1 AC1 14 LEU A1122 ALA A1148 MET A1196 GLU A1197
SITE 2 AC1 14 MET A1199 ALA A1200 GLY A1202 ARG A1253
SITE 3 AC1 14 ASN A1254 LEU A1256 GLY A1269 ASP A1270
SITE 4 AC1 14 HOH A2094 HOH A2097
CRYST1 51.721 57.174 105.253 90.00 90.00 90.00 P 21 21 21 4
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 0.019335 0.000000 0.000000 0.00000
SCALE2 0.000000 0.017490 0.000000 0.00000
SCALE3 0.000000 0.000000 0.009501 0.00000
(ATOM LINES ARE NOT SHOWN.)
END
