HEADER TRANSFERASE 24-JAN-08 3C1X
TITLE CRYSTAL STRUCTURE OF THE TYROSINE KINASE DOMAIN OF THE HEPATOCYTE
TITLE 2 GROWTH FACTOR RECEPTOR C-MET IN COMPLEX WITH A PYRROLOTRIAZINE BASED
TITLE 3 INHIBITOR
COMPND MOL_ID: 1;
COMPND 2 MOLECULE: HEPATOCYTE GROWTH FACTOR RECEPTOR;
COMPND 3 CHAIN: A;
COMPND 4 FRAGMENT: TYROSINE KINASE DOMAIN, UNP RESIDUES 1049-1360;
COMPND 5 SYNONYM: MET PROTO-ONCOGENE TYROSINE KINASE, C-MET, HGF RECEPTOR,
COMPND 6 HGF/SF RECEPTOR, SF RECEPTOR, SCATTER FACTOR RECEPTOR;
COMPND 7 EC: 2.7.10.1;
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: MET;
SOURCE 6 EXPRESSION_SYSTEM: SPODOPTERA FRUGIPERDA;
SOURCE 7 EXPRESSION_SYSTEM_COMMON: FALL ARMYWORM;
SOURCE 8 EXPRESSION_SYSTEM_TAXID: 7108;
SOURCE 9 EXPRESSION_SYSTEM_CELL_LINE: SPODOPTERA FRUGIPERDA 9 (SF9);
SOURCE 10 EXPRESSION_SYSTEM_VECTOR_TYPE: BACULOVIRUS;
SOURCE 11 EXPRESSION_SYSTEM_VECTOR: PACHLT-A
KEYWDS RECEPTOR TYROSINE KINASE, SIGNAL TRANSDUCTION, GRB2, SHC, ATP-
KEYWDS 2 BINDING, GLYCOPROTEIN, MEMBRANE, NUCLEOTIDE-BINDING, PHOSPHOPROTEIN,
KEYWDS 3 PROTO-ONCOGENE, TRANSFERASE, TRANSMEMBRANE, TYROSINE-PROTEIN KINASE
EXPDTA X-RAY DIFFRACTION
AUTHOR J.SACK
REVDAT 5 21-FEB-24 3C1X 1 REMARK
REVDAT 4 20-OCT-21 3C1X 1 REMARK SEQADV
REVDAT 3 24-FEB-09 3C1X 1 VERSN
REVDAT 2 06-MAY-08 3C1X 1 JRNL
REVDAT 1 18-MAR-08 3C1X 0
JRNL AUTH G.M.SCHROEDER,X.T.CHEN,D.K.WILLIAMS,D.S.NIRSCHL,Z.W.CAI,
JRNL AUTH 2 D.WEI,J.S.TOKARSKI,Y.AN,J.SACK,Z.CHEN,T.HUYNH,W.VACCARO,
JRNL AUTH 3 M.POSS,B.WAUTLET,J.GULLO-BROWN,K.KELLAR,V.MANNE,J.T.HUNT,
JRNL AUTH 4 T.W.WONG,L.J.LOMBARDO,J.FARGNOLI,R.M.BORZILLERI
JRNL TITL IDENTIFICATION OF PYRROLO[2,1-F][1,2,4]TRIAZINE-BASED
JRNL TITL 2 INHIBITORS OF MET KINASE.
JRNL REF BIOORG.MED.CHEM.LETT. V. 18 1945 2008
JRNL REFN ISSN 0960-894X
JRNL PMID 18289854
JRNL DOI 10.1016/J.BMCL.2008.01.121
REMARK 2
REMARK 2 RESOLUTION. 2.17 ANGSTROMS.
REMARK 3
REMARK 3 REFINEMENT.
REMARK 3 PROGRAM : BUSTER-TNT 2.1.1
REMARK 3 AUTHORS : BRICOGNE,BLANC,BRANDL,FLENSBURG,KELLER,
REMARK 3 : PACIOREK,ROVERSI,SMART,VONRHEIN,WOMACK,
REMARK 3 : MATTHEWS,TEN EYCK,TRONRUD
REMARK 3
REMARK 3 DATA USED IN REFINEMENT.
REMARK 3 RESOLUTION RANGE HIGH (ANGSTROMS) : 2.17
REMARK 3 RESOLUTION RANGE LOW (ANGSTROMS) : 37.76
REMARK 3 DATA CUTOFF (SIGMA(F)) : 0.000
REMARK 3 COMPLETENESS FOR RANGE (%) : 80.5
REMARK 3 NUMBER OF REFLECTIONS : 13241
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) : 0.208
REMARK 3 R VALUE (WORKING SET) : 0.205
REMARK 3 FREE R VALUE : 0.262
REMARK 3 FREE R VALUE TEST SET SIZE (%) : 5.970
REMARK 3 FREE R VALUE TEST SET COUNT : 791
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 : 9
REMARK 3 BIN RESOLUTION RANGE HIGH (ANGSTROMS) : 2.17
REMARK 3 BIN RESOLUTION RANGE LOW (ANGSTROMS) : 2.31
REMARK 3 BIN COMPLETENESS (WORKING+TEST) (%) : 80.48
REMARK 3 REFLECTIONS IN BIN (WORKING + TEST SET) : 1622
REMARK 3 BIN R VALUE (WORKING + TEST SET) : 0.2553
REMARK 3 REFLECTIONS IN BIN (WORKING SET) : 1545
REMARK 3 BIN R VALUE (WORKING SET) : 0.2524
REMARK 3 BIN FREE R VALUE : 0.3134
REMARK 3 BIN FREE R VALUE TEST SET SIZE (%) : 4.75
REMARK 3 BIN FREE R VALUE TEST SET COUNT : 77
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 : 2309
REMARK 3 NUCLEIC ACID ATOMS : 0
REMARK 3 HETEROGEN ATOMS : 39
REMARK 3 SOLVENT ATOMS : 92
REMARK 3
REMARK 3 B VALUES.
REMARK 3 FROM WILSON PLOT (A**2) : 43.35
REMARK 3 MEAN B VALUE (OVERALL, A**2) : 54.86
REMARK 3 OVERALL ANISOTROPIC B VALUE.
REMARK 3 B11 (A**2) : -2.98288
REMARK 3 B22 (A**2) : 4.35454
REMARK 3 B33 (A**2) : -1.37166
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) : NULL
REMARK 3 DPI (BLOW EQ-10) BASED ON R VALUE (A) : NULL
REMARK 3 DPI (BLOW EQ-9) BASED ON FREE R VALUE (A) : NULL
REMARK 3 DPI (CRUICKSHANK) BASED ON R VALUE (A) : NULL
REMARK 3 DPI (CRUICKSHANK) BASED ON FREE R VALUE (A) : NULL
REMARK 3
REMARK 3 REFERENCES: BLOW, D. (2002) ACTA CRYST D58, 792-797
REMARK 3 CRUICKSHANK, D.W.J. (1999) ACTA CRYST D55, 583-601
REMARK 3
REMARK 3 CORRELATION COEFFICIENTS.
REMARK 3 CORRELATION COEFFICIENT FO-FC : NULL
REMARK 3 CORRELATION COEFFICIENT FO-FC FREE : NULL
REMARK 3
REMARK 3 NUMBER OF GEOMETRIC FUNCTION TERMS DEFINED : 15
REMARK 3 TERM COUNT WEIGHT FUNCTION.
REMARK 3 BOND LENGTHS : 2410 ; 2.000 ; NULL
REMARK 3 BOND ANGLES : 3255 ; 2.000 ; NULL
REMARK 3 TORSION ANGLES : 463 ; 0.000 ; NULL
REMARK 3 TRIGONAL CARBON PLANES : 61 ; 2.000 ; NULL
REMARK 3 GENERAL PLANES : 344 ; 5.000 ; NULL
REMARK 3 ISOTROPIC THERMAL FACTORS : 2410 ; 20.000 ; NULL
REMARK 3 BAD NON-BONDED CONTACTS : 75 ; 5.000 ; NULL
REMARK 3 IMPROPER TORSIONS : NULL ; NULL ; NULL
REMARK 3 PSEUDOROTATION ANGLES : NULL ; NULL ; NULL
REMARK 3 CHIRAL IMPROPER TORSION : NULL ; NULL ; NULL
REMARK 3 SUM OF OCCUPANCIES : NULL ; NULL ; NULL
REMARK 3 UTILITY DISTANCES : NULL ; NULL ; NULL
REMARK 3 UTILITY ANGLES : NULL ; NULL ; NULL
REMARK 3 UTILITY TORSION : NULL ; NULL ; NULL
REMARK 3 IDEAL-DIST CONTACT TERM : NULL ; NULL ; NULL
REMARK 3
REMARK 3 RMS DEVIATIONS FROM IDEAL VALUES.
REMARK 3 BOND LENGTHS (A) : 0.004
REMARK 3 BOND ANGLES (DEGREES) : 0.75
REMARK 3 PEPTIDE OMEGA TORSION ANGLES (DEGREES) : NULL
REMARK 3 OTHER TORSION ANGLES (DEGREES) : NULL
REMARK 3
REMARK 3 TLS DETAILS
REMARK 3 NUMBER OF TLS GROUPS : NULL
REMARK 3
REMARK 3 OTHER REFINEMENT REMARKS: NULL
REMARK 4
REMARK 4 3C1X COMPLIES WITH FORMAT V. 3.30, 13-JUL-11
REMARK 100
REMARK 100 THIS ENTRY HAS BEEN PROCESSED BY RCSB ON 28-JAN-08.
REMARK 100 THE DEPOSITION ID IS D_1000046238.
REMARK 200
REMARK 200 EXPERIMENTAL DETAILS
REMARK 200 EXPERIMENT TYPE : X-RAY DIFFRACTION
REMARK 200 DATE OF DATA COLLECTION : 23-OCT-04
REMARK 200 TEMPERATURE (KELVIN) : 100
REMARK 200 PH : NULL
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) : 1.00
REMARK 200 MONOCHROMATOR : NULL
REMARK 200 OPTICS : NULL
REMARK 200
REMARK 200 DETECTOR TYPE : CCD
REMARK 200 DETECTOR MANUFACTURER : ADSC
REMARK 200 INTENSITY-INTEGRATION SOFTWARE : DENZO
REMARK 200 DATA SCALING SOFTWARE : SCALEPACK
REMARK 200
REMARK 200 NUMBER OF UNIQUE REFLECTIONS : 13241
REMARK 200 RESOLUTION RANGE HIGH (A) : 2.170
REMARK 200 RESOLUTION RANGE LOW (A) : 50.000
REMARK 200 REJECTION CRITERIA (SIGMA(I)) : 0.000
REMARK 200
REMARK 200 OVERALL.
REMARK 200 COMPLETENESS FOR RANGE (%) : 78.1
REMARK 200 DATA REDUNDANCY : 3.000
REMARK 200 R MERGE (I) : 0.10800
REMARK 200 R SYM (I) : NULL
REMARK 200 <I/SIGMA(I)> FOR THE DATA SET : 10.1000
REMARK 200
REMARK 200 IN THE HIGHEST RESOLUTION SHELL.
REMARK 200 HIGHEST RESOLUTION SHELL, RANGE HIGH (A) : 2.17
REMARK 200 HIGHEST RESOLUTION SHELL, RANGE LOW (A) : 2.37
REMARK 200 COMPLETENESS FOR SHELL (%) : 65.5
REMARK 200 DATA REDUNDANCY IN SHELL : 2.10
REMARK 200 R MERGE FOR SHELL (I) : 0.36100
REMARK 200 R SYM FOR SHELL (I) : NULL
REMARK 200 <I/SIGMA(I)> FOR SHELL : 1.700
REMARK 200
REMARK 200 DIFFRACTION PROTOCOL: SINGLE WAVELENGTH
REMARK 200 METHOD USED TO DETERMINE THE STRUCTURE: MOLECULAR REPLACEMENT
REMARK 200 SOFTWARE USED: AMORE
REMARK 200 STARTING MODEL: NULL
REMARK 200
REMARK 200 REMARK: NULL
REMARK 280
REMARK 280 CRYSTAL
REMARK 280 SOLVENT CONTENT, VS (%): 30.95
REMARK 280 MATTHEWS COEFFICIENT, VM (ANGSTROMS**3/DA): 1.78
REMARK 280
REMARK 280 CRYSTALLIZATION CONDITIONS: NULL
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 21.39050
REMARK 290 SMTRY2 2 0.000000 -1.000000 0.000000 0.00000
REMARK 290 SMTRY3 2 0.000000 0.000000 1.000000 75.51100
REMARK 290 SMTRY1 3 -1.000000 0.000000 0.000000 0.00000
REMARK 290 SMTRY2 3 0.000000 1.000000 0.000000 23.07650
REMARK 290 SMTRY3 3 0.000000 0.000000 -1.000000 75.51100
REMARK 290 SMTRY1 4 1.000000 0.000000 0.000000 21.39050
REMARK 290 SMTRY2 4 0.000000 -1.000000 0.000000 23.07650
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 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 988
REMARK 465 SER A 989
REMARK 465 PRO A 990
REMARK 465 ILE A 991
REMARK 465 ASP A 992
REMARK 465 PRO A 993
REMARK 465 MET A 994
REMARK 465 GLY A 995
REMARK 465 HIS A 996
REMARK 465 HIS A 997
REMARK 465 HIS A 998
REMARK 465 HIS A 999
REMARK 465 HIS A 1000
REMARK 465 HIS A 1001
REMARK 465 GLY A 1002
REMARK 465 ARG A 1003
REMARK 465 ARG A 1004
REMARK 465 ARG A 1005
REMARK 465 ALA A 1006
REMARK 465 SER A 1007
REMARK 465 VAL A 1008
REMARK 465 ALA A 1009
REMARK 465 ALA A 1010
REMARK 465 GLY A 1011
REMARK 465 ILE A 1012
REMARK 465 LEU A 1013
REMARK 465 VAL A 1014
REMARK 465 PRO A 1015
REMARK 465 ARG A 1016
REMARK 465 GLY A 1017
REMARK 465 SER A 1018
REMARK 465 PRO A 1019
REMARK 465 GLY A 1020
REMARK 465 LEU A 1021
REMARK 465 ASP A 1022
REMARK 465 GLY A 1023
REMARK 465 ILE A 1024
REMARK 465 CYS A 1025
REMARK 465 SER A 1026
REMARK 465 ILE A 1027
REMARK 465 GLU A 1028
REMARK 465 GLU A 1029
REMARK 465 LEU A 1030
REMARK 465 SER A 1031
REMARK 465 THR A 1032
REMARK 465 SER A 1033
REMARK 465 LEU A 1034
REMARK 465 TYR A 1035
REMARK 465 LYS A 1036
REMARK 465 LYS A 1037
REMARK 465 ALA A 1038
REMARK 465 GLY A 1039
REMARK 465 SER A 1040
REMARK 465 GLU A 1041
REMARK 465 ASN A 1042
REMARK 465 LEU A 1043
REMARK 465 TYR A 1044
REMARK 465 PHE A 1045
REMARK 465 GLN A 1046
REMARK 465 GLY A 1047
REMARK 465 ALA A 1048
REMARK 465 ASN A 1049
REMARK 465 GLY A 1224
REMARK 465 LEU A 1225
REMARK 465 ALA A 1226
REMARK 465 ARG A 1227
REMARK 465 ASP A 1228
REMARK 465 MET A 1229
REMARK 465 TYR A 1230
REMARK 465 ASP A 1231
REMARK 465 LYS A 1232
REMARK 465 GLU A 1233
REMARK 465 PHE A 1234
REMARK 465 ASP A 1235
REMARK 465 SER A 1236
REMARK 465 VAL A 1237
REMARK 465 HIS A 1238
REMARK 465 ASN A 1239
REMARK 465 LYS A 1240
REMARK 465 THR A 1241
REMARK 465 GLY A 1242
REMARK 465 ALA A 1243
REMARK 465 LYS A 1244
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 PRO A1060 C - N - CD ANGL. DEV. = -16.1 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 HIS A1052 38.87 -99.98
REMARK 500 LEU A1058 -123.81 -64.75
REMARK 500 PRO A1060 -88.38 -30.04
REMARK 500 GLU A1061 31.58 -59.63
REMARK 500 LEU A1062 -67.47 -137.20
REMARK 500 VAL A1063 44.06 -102.45
REMARK 500 HIS A1068 13.52 -67.81
REMARK 500 SER A1074 39.88 -75.32
REMARK 500 SER A1075 -1.59 -177.53
REMARK 500 HIS A1079 79.68 -113.19
REMARK 500 HIS A1088 -41.33 -176.47
REMARK 500 ASP A1099 101.18 -57.58
REMARK 500 ASN A1100 -102.68 76.36
REMARK 500 LYS A1103 107.34 -54.00
REMARK 500 ASN A1113 -96.17 -44.95
REMARK 500 ARG A1114 -124.52 -169.04
REMARK 500 ASP A1117 176.28 90.56
REMARK 500 SER A1152 101.52 173.37
REMARK 500 ARG A1203 -12.42 82.48
REMARK 500 ASP A1204 46.97 -148.15
REMARK 500 GLN A1258 17.62 36.30
REMARK 500 ASN A1288 -39.69 -26.44
REMARK 500 THR A1289 99.29 39.99
REMARK 500 PHE A1290 -93.48 -57.81
REMARK 500 ASP A1291 29.41 19.99
REMARK 500 ASN A1358 -6.37 72.48
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 CKK A 1500
DBREF 3C1X A 1049 1360 UNP P08581 MET_HUMAN 1049 1360
SEQADV 3C1X MET A 988 UNP P08581 EXPRESSION TAG
SEQADV 3C1X SER A 989 UNP P08581 EXPRESSION TAG
SEQADV 3C1X PRO A 990 UNP P08581 EXPRESSION TAG
SEQADV 3C1X ILE A 991 UNP P08581 EXPRESSION TAG
SEQADV 3C1X ASP A 992 UNP P08581 EXPRESSION TAG
SEQADV 3C1X PRO A 993 UNP P08581 EXPRESSION TAG
SEQADV 3C1X MET A 994 UNP P08581 EXPRESSION TAG
SEQADV 3C1X GLY A 995 UNP P08581 EXPRESSION TAG
SEQADV 3C1X HIS A 996 UNP P08581 EXPRESSION TAG
SEQADV 3C1X HIS A 997 UNP P08581 EXPRESSION TAG
SEQADV 3C1X HIS A 998 UNP P08581 EXPRESSION TAG
SEQADV 3C1X HIS A 999 UNP P08581 EXPRESSION TAG
SEQADV 3C1X HIS A 1000 UNP P08581 EXPRESSION TAG
SEQADV 3C1X HIS A 1001 UNP P08581 EXPRESSION TAG
SEQADV 3C1X GLY A 1002 UNP P08581 EXPRESSION TAG
SEQADV 3C1X ARG A 1003 UNP P08581 EXPRESSION TAG
SEQADV 3C1X ARG A 1004 UNP P08581 EXPRESSION TAG
SEQADV 3C1X ARG A 1005 UNP P08581 EXPRESSION TAG
SEQADV 3C1X ALA A 1006 UNP P08581 EXPRESSION TAG
SEQADV 3C1X SER A 1007 UNP P08581 EXPRESSION TAG
SEQADV 3C1X VAL A 1008 UNP P08581 EXPRESSION TAG
SEQADV 3C1X ALA A 1009 UNP P08581 EXPRESSION TAG
SEQADV 3C1X ALA A 1010 UNP P08581 EXPRESSION TAG
SEQADV 3C1X GLY A 1011 UNP P08581 EXPRESSION TAG
SEQADV 3C1X ILE A 1012 UNP P08581 EXPRESSION TAG
SEQADV 3C1X LEU A 1013 UNP P08581 EXPRESSION TAG
SEQADV 3C1X VAL A 1014 UNP P08581 EXPRESSION TAG
SEQADV 3C1X PRO A 1015 UNP P08581 EXPRESSION TAG
SEQADV 3C1X ARG A 1016 UNP P08581 EXPRESSION TAG
SEQADV 3C1X GLY A 1017 UNP P08581 EXPRESSION TAG
SEQADV 3C1X SER A 1018 UNP P08581 EXPRESSION TAG
SEQADV 3C1X PRO A 1019 UNP P08581 EXPRESSION TAG
SEQADV 3C1X GLY A 1020 UNP P08581 EXPRESSION TAG
SEQADV 3C1X LEU A 1021 UNP P08581 EXPRESSION TAG
SEQADV 3C1X ASP A 1022 UNP P08581 EXPRESSION TAG
SEQADV 3C1X GLY A 1023 UNP P08581 EXPRESSION TAG
SEQADV 3C1X ILE A 1024 UNP P08581 EXPRESSION TAG
SEQADV 3C1X CYS A 1025 UNP P08581 EXPRESSION TAG
SEQADV 3C1X SER A 1026 UNP P08581 EXPRESSION TAG
SEQADV 3C1X ILE A 1027 UNP P08581 EXPRESSION TAG
SEQADV 3C1X GLU A 1028 UNP P08581 EXPRESSION TAG
SEQADV 3C1X GLU A 1029 UNP P08581 EXPRESSION TAG
SEQADV 3C1X LEU A 1030 UNP P08581 EXPRESSION TAG
SEQADV 3C1X SER A 1031 UNP P08581 EXPRESSION TAG
SEQADV 3C1X THR A 1032 UNP P08581 EXPRESSION TAG
SEQADV 3C1X SER A 1033 UNP P08581 EXPRESSION TAG
SEQADV 3C1X LEU A 1034 UNP P08581 EXPRESSION TAG
SEQADV 3C1X TYR A 1035 UNP P08581 EXPRESSION TAG
SEQADV 3C1X LYS A 1036 UNP P08581 EXPRESSION TAG
SEQADV 3C1X LYS A 1037 UNP P08581 EXPRESSION TAG
SEQADV 3C1X ALA A 1038 UNP P08581 EXPRESSION TAG
SEQADV 3C1X GLY A 1039 UNP P08581 EXPRESSION TAG
SEQADV 3C1X SER A 1040 UNP P08581 EXPRESSION TAG
SEQADV 3C1X GLU A 1041 UNP P08581 EXPRESSION TAG
SEQADV 3C1X ASN A 1042 UNP P08581 EXPRESSION TAG
SEQADV 3C1X LEU A 1043 UNP P08581 EXPRESSION TAG
SEQADV 3C1X TYR A 1044 UNP P08581 EXPRESSION TAG
SEQADV 3C1X PHE A 1045 UNP P08581 EXPRESSION TAG
SEQADV 3C1X GLN A 1046 UNP P08581 EXPRESSION TAG
SEQADV 3C1X GLY A 1047 UNP P08581 EXPRESSION TAG
SEQADV 3C1X ALA A 1048 UNP P08581 EXPRESSION TAG
SEQADV 3C1X PHE A 1194 UNP P08581 TYR 1194 ENGINEERED MUTATION
SEQADV 3C1X PHE A 1234 UNP P08581 TYR 1234 ENGINEERED MUTATION
SEQADV 3C1X ASP A 1235 UNP P08581 TYR 1235 ENGINEERED MUTATION
SEQADV 3C1X LEU A 1272 UNP P08581 VAL 1272 ENGINEERED MUTATION
SEQRES 1 A 373 MET SER PRO ILE ASP PRO MET GLY HIS HIS HIS HIS HIS
SEQRES 2 A 373 HIS GLY ARG ARG ARG ALA SER VAL ALA ALA GLY ILE LEU
SEQRES 3 A 373 VAL PRO ARG GLY SER PRO GLY LEU ASP GLY ILE CYS SER
SEQRES 4 A 373 ILE GLU GLU LEU SER THR SER LEU TYR LYS LYS ALA GLY
SEQRES 5 A 373 SER GLU ASN LEU TYR PHE GLN GLY ALA ASN THR VAL HIS
SEQRES 6 A 373 ILE ASP LEU SER ALA LEU ASN PRO GLU LEU VAL GLN ALA
SEQRES 7 A 373 VAL GLN HIS VAL VAL ILE GLY PRO SER SER LEU ILE VAL
SEQRES 8 A 373 HIS PHE ASN GLU VAL ILE GLY ARG GLY HIS PHE GLY CYS
SEQRES 9 A 373 VAL TYR HIS GLY THR LEU LEU ASP ASN ASP GLY LYS LYS
SEQRES 10 A 373 ILE HIS CYS ALA VAL LYS SER LEU ASN ARG ILE THR ASP
SEQRES 11 A 373 ILE GLY GLU VAL SER GLN PHE LEU THR GLU GLY ILE ILE
SEQRES 12 A 373 MET LYS ASP PHE SER HIS PRO ASN VAL LEU SER LEU LEU
SEQRES 13 A 373 GLY ILE CYS LEU ARG SER GLU GLY SER PRO LEU VAL VAL
SEQRES 14 A 373 LEU PRO TYR MET LYS HIS GLY ASP LEU ARG ASN PHE ILE
SEQRES 15 A 373 ARG ASN GLU THR HIS ASN PRO THR VAL LYS ASP LEU ILE
SEQRES 16 A 373 GLY PHE GLY LEU GLN VAL ALA LYS GLY MET LYS PHE LEU
SEQRES 17 A 373 ALA SER LYS LYS PHE VAL HIS ARG ASP LEU ALA ALA ARG
SEQRES 18 A 373 ASN CYS MET LEU ASP GLU LYS PHE THR VAL LYS VAL ALA
SEQRES 19 A 373 ASP PHE GLY LEU ALA ARG ASP MET TYR ASP LYS GLU PHE
SEQRES 20 A 373 ASP SER VAL HIS ASN LYS THR GLY ALA LYS LEU PRO VAL
SEQRES 21 A 373 LYS TRP MET ALA LEU GLU SER LEU GLN THR GLN LYS PHE
SEQRES 22 A 373 THR THR LYS SER ASP VAL TRP SER PHE GLY VAL LEU LEU
SEQRES 23 A 373 TRP GLU LEU MET THR ARG GLY ALA PRO PRO TYR PRO ASP
SEQRES 24 A 373 VAL ASN THR PHE ASP ILE THR VAL TYR LEU LEU GLN GLY
SEQRES 25 A 373 ARG ARG LEU LEU GLN PRO GLU TYR CYS PRO ASP PRO LEU
SEQRES 26 A 373 TYR GLU VAL MET LEU LYS CYS TRP HIS PRO LYS ALA GLU
SEQRES 27 A 373 MET ARG PRO SER PHE SER GLU LEU VAL SER ARG ILE SER
SEQRES 28 A 373 ALA ILE PHE SER THR PHE ILE GLY GLU HIS TYR VAL HIS
SEQRES 29 A 373 VAL ASN ALA THR TYR VAL ASN VAL LYS
HET CKK A1500 39
HETNAM CKK N-{[4-({5-[(4-AMINOPIPERIDIN-1-YL)METHYL]PYRROLO[2,1-
HETNAM 2 CKK F][1,2,4]TRIAZIN-4-YL}OXY)-3-FLUOROPHENYL]CARBAMOYL}-
HETNAM 3 CKK 2-(4-FLUOROPHENYL)ACETAMIDE
FORMUL 2 CKK C27 H27 F2 N7 O3
FORMUL 3 HOH *92(H2 O)
HELIX 1 1 ASN A 1059 GLN A 1064 1 6
HELIX 2 2 ILE A 1118 ILE A 1129 1 12
HELIX 3 3 ASP A 1164 ASN A 1171 1 8
HELIX 4 4 THR A 1177 LYS A 1198 1 22
HELIX 5 5 ALA A 1206 ARG A 1208 5 3
HELIX 6 6 PRO A 1246 MET A 1250 5 5
HELIX 7 7 ALA A 1251 GLN A 1258 1 8
HELIX 8 8 THR A 1261 THR A 1278 1 18
HELIX 9 9 ASP A 1291 GLN A 1298 1 8
HELIX 10 10 PRO A 1309 TRP A 1320 1 12
HELIX 11 11 LYS A 1323 ARG A 1327 5 5
HELIX 12 12 SER A 1329 THR A 1343 1 15
SHEET 1 A 5 LEU A1076 GLY A1085 0
SHEET 2 A 5 CYS A1091 ASP A1099 -1 O THR A1096 N ILE A1077
SHEET 3 A 5 LYS A1103 SER A1111 -1 O LYS A1103 N ASP A1099
SHEET 4 A 5 LEU A1154 PRO A1158 -1 O LEU A1157 N ALA A1108
SHEET 5 A 5 GLY A1144 CYS A1146 -1 N GLY A1144 O VAL A1156
SHEET 1 B 2 CYS A1210 LEU A1212 0
SHEET 2 B 2 VAL A1218 VAL A1220 -1 O LYS A1219 N MET A1211
CISPEP 1 THR A 1289 PHE A 1290 0 3.93
SITE 1 AC1 17 ALA A1108 LYS A1110 GLU A1127 MET A1131
SITE 2 AC1 17 LEU A1140 LEU A1157 PRO A1158 TYR A1159
SITE 3 AC1 17 MET A1160 ASP A1164 LEU A1195 HIS A1202
SITE 4 AC1 17 ARG A1208 MET A1211 ALA A1221 ASP A1222
SITE 5 AC1 17 PHE A1223
CRYST1 42.781 46.153 151.022 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 0.023375 0.000000 0.000000 0.00000
SCALE2 0.000000 0.021667 0.000000 0.00000
SCALE3 0.000000 0.000000 0.006622 0.00000
(ATOM LINES ARE NOT SHOWN.)
END
