HEADER TRANSFERASE 06-JUN-11 2YM7
TITLE CRYSTAL STRUCTURE OF CHECKPOINT KINASE 1 (CHK1) IN COMPLEX WITH
TITLE 2 INHIBITORS
COMPND MOL_ID: 1;
COMPND 2 MOLECULE: SERINE/THREONINE-PROTEIN KINASE CHK1;
COMPND 3 CHAIN: A;
COMPND 4 FRAGMENT: KINASE DOMAIN, RESIDUES 1-289;
COMPND 5 SYNONYM: CHECKPOINT KINASE 1;
COMPND 6 EC: 2.7.11.1;
COMPND 7 ENGINEERED: 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
KEYWDS TRANSFERASE, DNA REPAIR, CELL CYCLE
EXPDTA X-RAY DIFFRACTION
AUTHOR J.C.READER,T.P.MATTHEWS,S.KLAIR,K.M.J.CHEUNG,J.SCANLON,N.PROISY,
AUTHOR 2 G.ADDISON,J.ELLARD,N.PITON,S.TAYLOR,M.CHERRY,M.FISHER,K.BOXALL,
AUTHOR 3 S.BURNS,M.I.WALTON,I.M.WESTWOOD,A.HAYES,P.EVE,M.VALENTI,A.H.BRANDON,
AUTHOR 4 G.BOX,R.L.M.VANMONTFORT,D.H.WILLIAMS,G.W.AHERNE,F.I.RAYNAUD,
AUTHOR 5 S.A.ECCLES,M.D.GARRETT,I.COLLINS
REVDAT 3 20-DEC-23 2YM7 1 REMARK
REVDAT 2 28-JUN-17 2YM7 1 REMARK
REVDAT 1 11-JAN-12 2YM7 0
JRNL AUTH J.C.READER,T.P.MATTHEWS,S.KLAIR,K.M.J.CHEUNG,J.SCANLON,
JRNL AUTH 2 N.PROISY,G.ADDISON,J.ELLARD,N.PITON,S.TAYLOR,M.CHERRY,
JRNL AUTH 3 M.FISHER,K.BOXALL,S.BURNS,M.I.WALTON,I.M.WESTWOOD,A.HAYES,
JRNL AUTH 4 P.EVE,M.VALENTI,A.DE HAVEN BRANDON,G.BOX,R.L.M.VAN MONTFORT,
JRNL AUTH 5 D.H.WILLIAMS,G.W.AHERNE,F.I.RAYNAUD,S.A.ECCLES,M.D.GARRETT,
JRNL AUTH 6 I.COLLINS
JRNL TITL STRUCTURE-GUIDED EVOLUTION OF POTENT AND SELECTIVE CHK1
JRNL TITL 2 INHIBITORS THROUGH SCAFFOLD MORPHING.
JRNL REF J.MED.CHEM. V. 54 8328 2011
JRNL REFN ISSN 0022-2623
JRNL PMID 22111927
JRNL DOI 10.1021/JM2007326
REMARK 1
REMARK 1 REFERENCE 1
REMARK 1 AUTH T.P.MATTHEWS,S.KLAIR,S.BURNS,K.BOXALL,M.CHERRY,M.FISHER,
REMARK 1 AUTH 2 I.M.WESTWOOD,M.I.WALTON,T.MCHARDY,K.-M.J.CHEUNG,
REMARK 1 AUTH 3 R.VAN MONTFORT,D.WILLIAMS,G.W.AHERNE,M.D.GARRETT,J.READER,
REMARK 1 AUTH 4 I.COLLINS
REMARK 1 TITL IDENTIFICATION OF INHIBITORS OF CHECKPOINT KINASE 1 THROUGH
REMARK 1 TITL 2 TEMPLATE SCREENING
REMARK 1 REF J.MED.CHEM. V. 52 4810 2009
REMARK 1 REFN ISSN 0022-2623
REMARK 1 PMID 19572549
REMARK 1 DOI 10.1021/JM900314J
REMARK 1 REFERENCE 2
REMARK 1 AUTH T.P.MATTHEWS,T.MCHARDY,S.KLAIR,K.BOXALL,M.FISHER,M.CHERRY,
REMARK 1 AUTH 2 C.E.ALLEN,G.J.ADDISON,J.ELLARD,G.W.AHERNE,I.M.WESTWOOD,
REMARK 1 AUTH 3 R.L.M.VAN MONTFORT,M.D.GARRETT,J.C.READER,I.COLLINS
REMARK 1 TITL DESIGN AND EVALUATION OF 3,6-DI(HETERO)ARYL
REMARK 1 TITL 2 IMIDAZO(1,2-A)PYRAZINES AS INHIBITORS OF CHECKPOINT AND
REMARK 1 TITL 3 OTHER KINASES
REMARK 1 REF BIOORG.MED.CHEM.LETT. V. 20 4045 2010
REMARK 1 REFN ISSN 0960-894X
REMARK 1 PMID 20561787
REMARK 1 DOI 10.1016/J.BMCL.2010.05.096
REMARK 2
REMARK 2 RESOLUTION. 1.81 ANGSTROMS.
REMARK 3
REMARK 3 REFINEMENT.
REMARK 3 PROGRAM : PHENIX (PHENIX.REFINE)
REMARK 3 AUTHORS : PAUL ADAMS,PAVEL AFONINE,VINCENT CHEN,IAN
REMARK 3 : DAVIS,KRESHNA GOPAL,RALF GROSSE-KUNSTLEVE,
REMARK 3 : LI-WEI HUNG,ROBERT IMMORMINO,TOM IOERGER,
REMARK 3 : AIRLIE MCCOY,ERIK MCKEE,NIGEL MORIARTY,
REMARK 3 : REETAL PAI,RANDY READ,JANE RICHARDSON,
REMARK 3 : DAVID RICHARDSON,TOD ROMO,JIM SACCHETTINI,
REMARK 3 : NICHOLAS SAUTER,JACOB SMITH,LAURENT
REMARK 3 : STORONI,TOM TERWILLIGER,PETER ZWART
REMARK 3
REMARK 3 REFINEMENT TARGET : ML
REMARK 3
REMARK 3 DATA USED IN REFINEMENT.
REMARK 3 RESOLUTION RANGE HIGH (ANGSTROMS) : 1.81
REMARK 3 RESOLUTION RANGE LOW (ANGSTROMS) : 34.24
REMARK 3 MIN(FOBS/SIGMA_FOBS) : 1.300
REMARK 3 COMPLETENESS FOR RANGE (%) : 87.1
REMARK 3 NUMBER OF REFLECTIONS : 52393
REMARK 3
REMARK 3 FIT TO DATA USED IN REFINEMENT.
REMARK 3 R VALUE (WORKING + TEST SET) : 0.174
REMARK 3 R VALUE (WORKING SET) : 0.173
REMARK 3 FREE R VALUE : 0.204
REMARK 3 FREE R VALUE TEST SET SIZE (%) : 4.900
REMARK 3 FREE R VALUE TEST SET COUNT : 2572
REMARK 3
REMARK 3 FIT TO DATA USED IN REFINEMENT (IN BINS).
REMARK 3 BIN RESOLUTION RANGE COMPL. NWORK NFREE RWORK RFREE
REMARK 3 1 34.2470 - 4.7422 0.83 2614 145 0.1854 0.1852
REMARK 3 2 4.7422 - 3.7656 0.85 2668 165 0.1303 0.1754
REMARK 3 3 3.7656 - 3.2900 0.85 2693 169 0.1501 0.1764
REMARK 3 4 3.2900 - 2.9894 0.86 2713 136 0.1571 0.2330
REMARK 3 5 2.9894 - 2.7752 0.86 2712 183 0.1549 0.1623
REMARK 3 6 2.7752 - 2.6117 0.87 2730 138 0.1529 0.1749
REMARK 3 7 2.6117 - 2.4809 0.87 2781 154 0.1665 0.2183
REMARK 3 8 2.4809 - 2.3729 0.87 2792 135 0.1610 0.1991
REMARK 3 9 2.3729 - 2.2816 0.88 2808 123 0.1624 0.2063
REMARK 3 10 2.2816 - 2.2029 0.88 2809 126 0.1674 0.2082
REMARK 3 11 2.2029 - 2.1340 0.88 2783 145 0.1782 0.2326
REMARK 3 12 2.1340 - 2.0730 0.88 2838 148 0.1768 0.2107
REMARK 3 13 2.0730 - 2.0185 0.89 2821 148 0.1831 0.2514
REMARK 3 14 2.0185 - 1.9692 0.89 2856 124 0.2110 0.2070
REMARK 3 15 1.9692 - 1.9245 0.89 2838 130 0.2432 0.3007
REMARK 3 16 1.9245 - 1.8835 0.89 2831 138 0.2921 0.3062
REMARK 3 17 1.8835 - 1.8458 0.89 2879 132 0.3357 0.3816
REMARK 3 18 1.8458 - 1.8110 0.85 2655 133 0.3764 0.3867
REMARK 3
REMARK 3 BULK SOLVENT MODELLING.
REMARK 3 METHOD USED : FLAT BULK SOLVENT MODEL
REMARK 3 SOLVENT RADIUS : 0.90
REMARK 3 SHRINKAGE RADIUS : 0.61
REMARK 3 K_SOL : 0.42
REMARK 3 B_SOL : 51.57
REMARK 3
REMARK 3 ERROR ESTIMATES.
REMARK 3 COORDINATE ERROR (MAXIMUM-LIKELIHOOD BASED) : 0.210
REMARK 3 PHASE ERROR (DEGREES, MAXIMUM-LIKELIHOOD BASED) : 19.830
REMARK 3
REMARK 3 B VALUES.
REMARK 3 FROM WILSON PLOT (A**2) : 23.63
REMARK 3 MEAN B VALUE (OVERALL, A**2) : 31.60
REMARK 3 OVERALL ANISOTROPIC B VALUE.
REMARK 3 B11 (A**2) : -2.87310
REMARK 3 B22 (A**2) : 2.29520
REMARK 3 B33 (A**2) : 0.57790
REMARK 3 B12 (A**2) : 0.00000
REMARK 3 B13 (A**2) : -0.23660
REMARK 3 B23 (A**2) : 0.00000
REMARK 3
REMARK 3 TWINNING INFORMATION.
REMARK 3 FRACTION: NULL
REMARK 3 OPERATOR: NULL
REMARK 3
REMARK 3 DEVIATIONS FROM IDEAL VALUES.
REMARK 3 RMSD COUNT
REMARK 3 BOND : 0.006 2162
REMARK 3 ANGLE : 1.004 2919
REMARK 3 CHIRALITY : 0.068 313
REMARK 3 PLANARITY : 0.005 369
REMARK 3 DIHEDRAL : 14.237 833
REMARK 3
REMARK 3 TLS DETAILS
REMARK 3 NUMBER OF TLS GROUPS : 7
REMARK 3 TLS GROUP : 1
REMARK 3 SELECTION: CHAIN A AND (RESSEQ 7:51)
REMARK 3 ORIGIN FOR THE GROUP (A): 11.7293 -1.5232 0.1800
REMARK 3 T TENSOR
REMARK 3 T11: 0.4887 T22: 0.4352
REMARK 3 T33: 0.1422 T12: -0.0657
REMARK 3 T13: -0.0006 T23: -0.0603
REMARK 3 L TENSOR
REMARK 3 L11: 0.1241 L22: 0.2318
REMARK 3 L33: 0.2150 L12: 0.1105
REMARK 3 L13: -0.1605 L23: -0.1727
REMARK 3 S TENSOR
REMARK 3 S11: 0.1489 S12: 0.2292 S13: 0.0028
REMARK 3 S21: 0.2390 S22: -0.0130 S23: 0.0007
REMARK 3 S31: 0.2203 S32: 0.0466 S33: -0.0795
REMARK 3 TLS GROUP : 2
REMARK 3 SELECTION: CHAIN A AND (RESSEQ 52:85)
REMARK 3 ORIGIN FOR THE GROUP (A): 3.7759 2.1898 10.4777
REMARK 3 T TENSOR
REMARK 3 T11: 0.2770 T22: 0.5086
REMARK 3 T33: 0.0064 T12: -0.1241
REMARK 3 T13: -0.1009 T23: -0.0362
REMARK 3 L TENSOR
REMARK 3 L11: 0.2182 L22: 0.0634
REMARK 3 L33: 0.0322 L12: -0.0476
REMARK 3 L13: -0.0553 L23: 0.0005
REMARK 3 S TENSOR
REMARK 3 S11: -0.0472 S12: 0.6773 S13: 0.2391
REMARK 3 S21: -0.3095 S22: -0.0293 S23: 0.0998
REMARK 3 S31: 0.0263 S32: -0.3395 S33: -0.0058
REMARK 3 TLS GROUP : 3
REMARK 3 SELECTION: CHAIN A AND (RESSEQ 86:103)
REMARK 3 ORIGIN FOR THE GROUP (A): 27.3465 2.8031 17.2198
REMARK 3 T TENSOR
REMARK 3 T11: 0.2119 T22: 0.2526
REMARK 3 T33: 0.1670 T12: -0.0000
REMARK 3 T13: 0.0588 T23: -0.0491
REMARK 3 L TENSOR
REMARK 3 L11: 0.6334 L22: 1.1710
REMARK 3 L33: 0.4210 L12: 0.2886
REMARK 3 L13: -0.3271 L23: 0.3394
REMARK 3 S TENSOR
REMARK 3 S11: -0.1128 S12: 0.4363 S13: -0.1224
REMARK 3 S21: -0.1947 S22: 0.0844 S23: -0.3902
REMARK 3 S31: 0.0772 S32: -0.0766 S33: -0.0140
REMARK 3 TLS GROUP : 4
REMARK 3 SELECTION: CHAIN A AND (RESSEQ 104:161)
REMARK 3 ORIGIN FOR THE GROUP (A): 12.1029 7.6826 22.1434
REMARK 3 T TENSOR
REMARK 3 T11: 0.1231 T22: 0.1041
REMARK 3 T33: 0.1060 T12: 0.0015
REMARK 3 T13: -0.0130 T23: 0.0155
REMARK 3 L TENSOR
REMARK 3 L11: 0.6430 L22: 0.5860
REMARK 3 L33: 0.2212 L12: 0.1440
REMARK 3 L13: 0.1514 L23: 0.1580
REMARK 3 S TENSOR
REMARK 3 S11: -0.0809 S12: 0.1455 S13: 0.0800
REMARK 3 S21: -0.1522 S22: 0.0337 S23: 0.0743
REMARK 3 S31: -0.0491 S32: -0.0354 S33: -0.0263
REMARK 3 TLS GROUP : 5
REMARK 3 SELECTION: CHAIN A AND (RESSEQ 162:185)
REMARK 3 ORIGIN FOR THE GROUP (A): 7.5614 -3.0761 34.7026
REMARK 3 T TENSOR
REMARK 3 T11: 0.1450 T22: 0.1487
REMARK 3 T33: 0.1733 T12: -0.0106
REMARK 3 T13: 0.0251 T23: 0.0195
REMARK 3 L TENSOR
REMARK 3 L11: 0.1875 L22: 0.5669
REMARK 3 L33: 0.7029 L12: 0.2928
REMARK 3 L13: -0.1704 L23: -0.2185
REMARK 3 S TENSOR
REMARK 3 S11: -0.0828 S12: -0.0316 S13: -0.1727
REMARK 3 S21: 0.0572 S22: 0.0231 S23: 0.0900
REMARK 3 S31: 0.1468 S32: -0.1437 S33: 0.0352
REMARK 3 TLS GROUP : 6
REMARK 3 SELECTION: CHAIN A AND (RESSEQ 186:255)
REMARK 3 ORIGIN FOR THE GROUP (A): 22.9953 2.8172 36.8910
REMARK 3 T TENSOR
REMARK 3 T11: 0.1172 T22: 0.1601
REMARK 3 T33: 0.1371 T12: 0.0041
REMARK 3 T13: -0.0089 T23: 0.0443
REMARK 3 L TENSOR
REMARK 3 L11: 0.2323 L22: 0.3784
REMARK 3 L33: 0.2990 L12: 0.2658
REMARK 3 L13: -0.0551 L23: -0.1601
REMARK 3 S TENSOR
REMARK 3 S11: -0.0074 S12: -0.2407 S13: -0.1014
REMARK 3 S21: 0.0422 S22: -0.0733 S23: -0.0990
REMARK 3 S31: -0.0241 S32: 0.0882 S33: 0.0385
REMARK 3 TLS GROUP : 7
REMARK 3 SELECTION: CHAIN A AND (RESSEQ 256:271)
REMARK 3 ORIGIN FOR THE GROUP (A): 23.0999 18.7006 30.0982
REMARK 3 T TENSOR
REMARK 3 T11: 0.1757 T22: 0.1080
REMARK 3 T33: 0.2582 T12: 0.0112
REMARK 3 T13: 0.0441 T23: 0.0140
REMARK 3 L TENSOR
REMARK 3 L11: 0.0956 L22: 0.1179
REMARK 3 L33: 0.1214 L12: -0.0451
REMARK 3 L13: -0.0303 L23: 0.1010
REMARK 3 S TENSOR
REMARK 3 S11: 0.0847 S12: -0.0136 S13: 0.3266
REMARK 3 S21: 0.0258 S22: -0.0635 S23: -0.2287
REMARK 3 S31: -0.1386 S32: 0.0415 S33: -0.0626
REMARK 3
REMARK 3 NCS DETAILS
REMARK 3 NUMBER OF NCS GROUPS : NULL
REMARK 3
REMARK 3 OTHER REFINEMENT REMARKS: RESIDUES 1-6, 17-21, 41-50, 77, 78, 272
REMARK 3 -289 ARE DISORDERED
REMARK 4
REMARK 4 2YM7 COMPLIES WITH FORMAT V. 3.30, 13-JUL-11
REMARK 100
REMARK 100 THIS ENTRY HAS BEEN PROCESSED BY PDBE ON 06-JUN-11.
REMARK 100 THE DEPOSITION ID IS D_1290048553.
REMARK 200
REMARK 200 EXPERIMENTAL DETAILS
REMARK 200 EXPERIMENT TYPE : X-RAY DIFFRACTION
REMARK 200 DATE OF DATA COLLECTION : 25-OCT-06
REMARK 200 TEMPERATURE (KELVIN) : 100
REMARK 200 PH : NULL
REMARK 200 NUMBER OF CRYSTALS USED : 1
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 MICROMAX-007 HF
REMARK 200 MONOCHROMATIC OR LAUE (M/L) : M
REMARK 200 WAVELENGTH OR RANGE (A) : 1.5418
REMARK 200 MONOCHROMATOR : NULL
REMARK 200 OPTICS : NULL
REMARK 200
REMARK 200 DETECTOR TYPE : CCD
REMARK 200 DETECTOR MANUFACTURER : RIGAKU CCD
REMARK 200 INTENSITY-INTEGRATION SOFTWARE : MOSFLM
REMARK 200 DATA SCALING SOFTWARE : SCALA
REMARK 200
REMARK 200 NUMBER OF UNIQUE REFLECTIONS : 29617
REMARK 200 RESOLUTION RANGE HIGH (A) : 1.810
REMARK 200 RESOLUTION RANGE LOW (A) : 36.730
REMARK 200 REJECTION CRITERIA (SIGMA(I)) : 1.500
REMARK 200
REMARK 200 OVERALL.
REMARK 200 COMPLETENESS FOR RANGE (%) : 96.7
REMARK 200 DATA REDUNDANCY : 2.500
REMARK 200 R MERGE (I) : 0.05000
REMARK 200 R SYM (I) : NULL
REMARK 200 <I/SIGMA(I)> FOR THE DATA SET : 12.2000
REMARK 200
REMARK 200 IN THE HIGHEST RESOLUTION SHELL.
REMARK 200 HIGHEST RESOLUTION SHELL, RANGE HIGH (A) : 1.81
REMARK 200 HIGHEST RESOLUTION SHELL, RANGE LOW (A) : 1.91
REMARK 200 COMPLETENESS FOR SHELL (%) : 99.3
REMARK 200 DATA REDUNDANCY IN SHELL : 2.30
REMARK 200 R MERGE FOR SHELL (I) : 0.49000
REMARK 200 R SYM FOR SHELL (I) : NULL
REMARK 200 <I/SIGMA(I)> FOR SHELL : 1.600
REMARK 200
REMARK 200 DIFFRACTION PROTOCOL: SINGLE WAVELENGTH
REMARK 200 METHOD USED TO DETERMINE THE STRUCTURE: MOLECULAR REPLACEMENT
REMARK 200 SOFTWARE USED: PHASER
REMARK 200 STARTING MODEL: PDB ENTRY 2WMW
REMARK 200
REMARK 200 REMARK: NONE
REMARK 280
REMARK 280 CRYSTAL
REMARK 280 SOLVENT CONTENT, VS (%): 58.50
REMARK 280 MATTHEWS COEFFICIENT, VM (ANGSTROMS**3/DA): 2.96
REMARK 280
REMARK 280 CRYSTALLIZATION CONDITIONS: DL-MALIC ACID/PEG3350
REMARK 290
REMARK 290 CRYSTALLOGRAPHIC SYMMETRY
REMARK 290 SYMMETRY OPERATORS FOR SPACE GROUP: P 1 21 1
REMARK 290
REMARK 290 SYMOP SYMMETRY
REMARK 290 NNNMMM OPERATOR
REMARK 290 1555 X,Y,Z
REMARK 290 2555 -X,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 0.00000
REMARK 290 SMTRY2 2 0.000000 1.000000 0.000000 32.85500
REMARK 290 SMTRY3 2 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 1
REMARK 465 ALA A 2
REMARK 465 VAL A 3
REMARK 465 PRO A 4
REMARK 465 PHE A 5
REMARK 465 VAL A 6
REMARK 465 GLU A 17
REMARK 465 GLY A 18
REMARK 465 ALA A 19
REMARK 465 TYR A 20
REMARK 465 GLY A 21
REMARK 465 ASP A 41
REMARK 465 MET A 42
REMARK 465 LYS A 43
REMARK 465 ARG A 44
REMARK 465 ALA A 45
REMARK 465 VAL A 46
REMARK 465 ASP A 47
REMARK 465 CYS A 48
REMARK 465 PRO A 49
REMARK 465 GLU A 50
REMARK 465 GLY A 77
REMARK 465 ASN A 78
REMARK 465 GLY A 272
REMARK 465 ALA A 273
REMARK 465 LYS A 274
REMARK 465 ARG A 275
REMARK 465 PRO A 276
REMARK 465 ARG A 277
REMARK 465 VAL A 278
REMARK 465 THR A 279
REMARK 465 SER A 280
REMARK 465 GLY A 281
REMARK 465 GLY A 282
REMARK 465 VAL A 283
REMARK 465 SER A 284
REMARK 465 GLU A 285
REMARK 465 SER A 286
REMARK 465 PRO A 287
REMARK 465 SER A 288
REMARK 465 GLY A 289
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 180 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 ASP A 99 -2.62 71.06
REMARK 500 ARG A 129 -7.11 79.62
REMARK 500 ASP A 130 47.00 -152.21
REMARK 500 ASP A 130 47.00 -147.89
REMARK 500 ASP A 148 94.15 75.02
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 A2017 DISTANCE = 6.00 ANGSTROMS
REMARK 800
REMARK 800 SITE
REMARK 800 SITE_IDENTIFIER: AC1
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: BINDING SITE FOR RESIDUE YM7 A 1272
REMARK 800
REMARK 800 SITE_IDENTIFIER: AC2
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: BINDING SITE FOR RESIDUE YM7 A 1273
REMARK 800
REMARK 800 SITE_IDENTIFIER: AC3
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: BINDING SITE FOR RESIDUE EDO A 1274
REMARK 800
REMARK 800 SITE_IDENTIFIER: AC4
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: BINDING SITE FOR RESIDUE EDO A 1275
REMARK 800
REMARK 800 SITE_IDENTIFIER: AC5
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: BINDING SITE FOR RESIDUE EDO A 1276
REMARK 800
REMARK 800 SITE_IDENTIFIER: AC6
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: BINDING SITE FOR RESIDUE EDO A 1277
REMARK 900
REMARK 900 RELATED ENTRIES
REMARK 900 RELATED ID: 2XF0 RELATED DB: PDB
REMARK 900 CRYSTAL STRUCTURE OF CHECKPOINT KINASE 1 (CHK1) IN COMPLEX WITH
REMARK 900 INHIBITORS
REMARK 900 RELATED ID: 2BRB RELATED DB: PDB
REMARK 900 STRUCTURE-BASED DESIGN OF NOVEL CHK1 INHIBITORS: INSIGHTS INTO
REMARK 900 HYDROGEN BONDING AND PROTEIN-LIGAND AFFINITY
REMARK 900 RELATED ID: 2X8D RELATED DB: PDB
REMARK 900 DISCOVERY OF A NOVEL CLASS OF TRIAZOLONES AS CHECKPOINT KINASE
REMARK 900 INHIBITORS - HIT TO LEAD EXPLORATION
REMARK 900 RELATED ID: 2WMR RELATED DB: PDB
REMARK 900 CRYSTAL STRUCTURE OF CHECKPOINT KINASE 1 (CHK1) IN COMPLEX WITH
REMARK 900 INHIBITORS
REMARK 900 RELATED ID: 2CGV RELATED DB: PDB
REMARK 900 IDENTIFICATION OF CHEMICALLY DIVERSE CHK1 INHIBITORS BY RECEPTOR-
REMARK 900 BASED VIRTUAL SCREENING
REMARK 900 RELATED ID: 2BRN RELATED DB: PDB
REMARK 900 STRUCTURE-BASED DESIGN OF NOVEL CHK1 INHIBITORS: INSIGHTS INTO
REMARK 900 HYDROGEN BONDING AND PROTEIN-LIGAND AFFINITY
REMARK 900 RELATED ID: 2WMX RELATED DB: PDB
REMARK 900 CRYSTAL STRUCTURE OF CHECKPOINT KINASE 1 (CHK1) IN COMPLEX WITH
REMARK 900 INHIBITORS
REMARK 900 RELATED ID: 2YER RELATED DB: PDB
REMARK 900 SYNTHESIS AND EVALUATION OF TRIAZOLONES AS CHECKPOINT KINASE 1
REMARK 900 INHIBITORS
REMARK 900 RELATED ID: 2AYP RELATED DB: PDB
REMARK 900 CRYSTAL STRUCTURE OF CHK1 WITH AN INDOL INHIBITOR
REMARK 900 RELATED ID: 2CGU RELATED DB: PDB
REMARK 900 IDENTIFICATION OF CHEMICALLY DIVERSE CHK1 INHIBITORS BY RECEPTOR-
REMARK 900 BASED VIRTUAL SCREENING
REMARK 900 RELATED ID: 1NVS RELATED DB: PDB
REMARK 900 THE COMPLEX STRUCTURE OF CHECKPOINT KINASE CHK1/SB218078
REMARK 900 RELATED ID: 2YDJ RELATED DB: PDB
REMARK 900 DISCOVERY OF CHECKPOINT KINASE INHIBITOR AZD7762 BY STRUCTURE BASED
REMARK 900 DESIGN AND OPTIMIZATION OF THIOPHENE CARBOXAMIDE UREAS
REMARK 900 RELATED ID: 1NVQ RELATED DB: PDB
REMARK 900 THE COMPLEX STRUCTURE OF CHECKPOINT KINASE CHK1/UCN-01
REMARK 900 RELATED ID: 2BRM RELATED DB: PDB
REMARK 900 STRUCTURE-BASED DESIGN OF NOVEL CHK1 INHIBITORS: INSIGHTS INTO
REMARK 900 HYDROGEN BONDING AND PROTEIN-LIGAND AFFINITY
REMARK 900 RELATED ID: 2YM5 RELATED DB: PDB
REMARK 900 CRYSTAL STRUCTURE OF CHECKPOINT KINASE 1 (CHK1) IN COMPLEX WITH
REMARK 900 INHIBITORS
REMARK 900 RELATED ID: 2YDI RELATED DB: PDB
REMARK 900 DISCOVERY OF CHECKPOINT KINASE INHIBITOR AZD7762 BY STRUCTURE BASED
REMARK 900 DESIGN AND OPTIMIZATION OF THIOPHENE CARBOXAMIDE UREAS
REMARK 900 RELATED ID: 2WMT RELATED DB: PDB
REMARK 900 CRYSTAL STRUCTURE OF CHECKPOINT KINASE 1 (CHK1) IN COMPLEX WITH
REMARK 900 INHIBITORS
REMARK 900 RELATED ID: 2CGX RELATED DB: PDB
REMARK 900 IDENTIFICATION OF CHEMICALLY DIVERSE CHK1 INHIBITORS BY RECEPTOR-
REMARK 900 BASED VIRTUAL SCREENING
REMARK 900 RELATED ID: 2C3J RELATED DB: PDB
REMARK 900 IDENTIFICATION OF A BURIED POCKET FOR POTENT AND SELECTIVE
REMARK 900 INHIBITION OF CHK1: PREDICTION AND VERIFICATION
REMARK 900 RELATED ID: 2BRO RELATED DB: PDB
REMARK 900 STRUCTURE-BASED DESIGN OF NOVEL CHK1 INHIBITORS: INSIGHTS INTO
REMARK 900 HYDROGEN BONDING AND PROTEIN-LIGAND AFFINITY
REMARK 900 RELATED ID: 2WMW RELATED DB: PDB
REMARK 900 CRYSTAL STRUCTURE OF CHECKPOINT KINASE 1 (CHK1) IN COMPLEX WITH
REMARK 900 INHIBITORS
REMARK 900 RELATED ID: 2WMU RELATED DB: PDB
REMARK 900 CRYSTAL STRUCTURE OF CHECKPOINT KINASE 1 (CHK1) IN COMPLEX WITH
REMARK 900 INHIBITORS
REMARK 900 RELATED ID: 2BRH RELATED DB: PDB
REMARK 900 STRUCTURE-BASED DESIGN OF NOVEL CHK1 INHIBITORS: INSIGHTS INTO
REMARK 900 HYDROGEN BONDING AND PROTEIN-LIGAND AFFINITY
REMARK 900 RELATED ID: 2X8E RELATED DB: PDB
REMARK 900 DISCOVERY OF A NOVEL CLASS OF TRIAZOLONES AS CHECKPOINT KINASE
REMARK 900 INHIBITORS - HIT TO LEAD EXPLORATION
REMARK 900 RELATED ID: 1NVR RELATED DB: PDB
REMARK 900 THE COMPLEX STRUCTURE OF CHECKPOINT KINASECHK1/ STAUROSPORINE
REMARK 900 RELATED ID: 2C3K RELATED DB: PDB
REMARK 900 IDENTIFICATION OF A BURIED POCKET FOR POTENT AND SELECTIVE
REMARK 900 INHIBITION OF CHK1: PREDICTION AND VERIFICATION
REMARK 900 RELATED ID: 2WMQ RELATED DB: PDB
REMARK 900 CRYSTAL STRUCTURE OF CHECKPOINT KINASE 1 (CHK1) IN COMPLEX WITH
REMARK 900 INHIBITORS
REMARK 900 RELATED ID: 2YM4 RELATED DB: PDB
REMARK 900 CRYSTAL STRUCTURE OF CHECKPOINT KINASE 1 (CHK1) IN COMPLEX WITH
REMARK 900 INHIBITORS
REMARK 900 RELATED ID: 2CGW RELATED DB: PDB
REMARK 900 IDENTIFICATION OF CHEMICALLY DIVERSE CHK1 INHIBITORS BY RECEPTOR-
REMARK 900 BASED VIRTUAL SCREENING
REMARK 900 RELATED ID: 1ZLT RELATED DB: PDB
REMARK 900 CRYSTAL STRUCTURE OF CHK1 COMPLEXED WITH A HYMENALDISINEANALOG
REMARK 900 RELATED ID: 2YEX RELATED DB: PDB
REMARK 900 SYNTHESIS AND EVALUATION OF TRIAZOLONES AS CHECKPOINT KINASE 1
REMARK 900 INHIBITORS
REMARK 900 RELATED ID: 2YM3 RELATED DB: PDB
REMARK 900 CRYSTAL STRUCTURE OF CHECKPOINT KINASE 1 (CHK1) IN COMPLEX WITH
REMARK 900 INHIBITORS
REMARK 900 RELATED ID: 2XEZ RELATED DB: PDB
REMARK 900 CRYSTAL STRUCTURE OF CHECKPOINT KINASE 1 (CHK1) IN COMPLEX WITH
REMARK 900 INHIBITORS
REMARK 900 RELATED ID: 1ZYS RELATED DB: PDB
REMARK 900 CO-CRYSTAL STRUCTURE OF CHECKPOINT KINASE CHK1 WITH APYRROLO-
REMARK 900 PYRIDINE INHIBITOR
REMARK 900 RELATED ID: 2BR1 RELATED DB: PDB
REMARK 900 STRUCTURE-BASED DESIGN OF NOVEL CHK1 INHIBITORS: INSIGHTS INTO
REMARK 900 HYDROGEN BONDING AND PROTEIN-LIGAND AFFINITY
REMARK 900 RELATED ID: 1IA8 RELATED DB: PDB
REMARK 900 THE 1.7 A CRYSTAL STRUCTURE OF HUMAN CELL CYCLE CHECKPOINTKINASE
REMARK 900 CHK1
REMARK 900 RELATED ID: 2BRG RELATED DB: PDB
REMARK 900 STRUCTURE-BASED DESIGN OF NOVEL CHK1 INHIBITORS: INSIGHTS INTO
REMARK 900 HYDROGEN BONDING AND PROTEIN-LIGAND AFFINITY
REMARK 900 RELATED ID: 2YDK RELATED DB: PDB
REMARK 900 DISCOVERY OF CHECKPOINT KINASE INHIBITOR AZD7762 BY STRUCTURE BASED
REMARK 900 DESIGN AND OPTIMIZATION OF THIOPHENE CARBOXAMIDE UREAS
REMARK 900 RELATED ID: 2WMV RELATED DB: PDB
REMARK 900 CRYSTAL STRUCTURE OF CHECKPOINT KINASE 1 (CHK1) IN COMPLEX WITH
REMARK 900 INHIBITORS
REMARK 900 RELATED ID: 2WMS RELATED DB: PDB
REMARK 900 CRYSTAL STRUCTURE OF CHECKPOINT KINASE 1 (CHK1) IN COMPLEX WITH
REMARK 900 INHIBITORS
REMARK 900 RELATED ID: 2X8I RELATED DB: PDB
REMARK 900 DISCOVERY OF A NOVEL CLASS OF TRIAZOLONES AS CHECKPOINT KINASE
REMARK 900 INHIBITORS - HIT TO LEAD EXPLORATION
REMARK 900 RELATED ID: 2C3L RELATED DB: PDB
REMARK 900 IDENTIFICATION OF A BURIED POCKET FOR POTENT AND SELECTIVE
REMARK 900 INHIBITION OF CHK1: PREDICTION AND VERIFICATION
REMARK 900 RELATED ID: 2XEY RELATED DB: PDB
REMARK 900 CRYSTAL STRUCTURE OF CHECKPOINT KINASE 1 (CHK1) IN COMPLEX WITH
REMARK 900 INHIBITORS
REMARK 900 RELATED ID: 2YM8 RELATED DB: PDB
REMARK 900 CRYSTAL STRUCTURE OF CHECKPOINT KINASE 1 (CHK1) IN COMPLEX WITH
REMARK 900 INHIBITORS
REMARK 900 RELATED ID: 2YM6 RELATED DB: PDB
REMARK 900 CRYSTAL STRUCTURE OF CHECKPOINT KINASE 1 (CHK1) IN COMPLEX WITH
REMARK 900 INHIBITORS
DBREF 2YM7 A 1 289 UNP O14757 CHK1_HUMAN 1 289
SEQRES 1 A 289 MET ALA VAL PRO PHE VAL GLU ASP TRP ASP LEU VAL GLN
SEQRES 2 A 289 THR LEU GLY GLU GLY ALA TYR GLY GLU VAL GLN LEU ALA
SEQRES 3 A 289 VAL ASN ARG VAL THR GLU GLU ALA VAL ALA VAL LYS ILE
SEQRES 4 A 289 VAL ASP MET LYS ARG ALA VAL ASP CYS PRO GLU ASN ILE
SEQRES 5 A 289 LYS LYS GLU ILE CYS ILE ASN LYS MET LEU ASN HIS GLU
SEQRES 6 A 289 ASN VAL VAL LYS PHE TYR GLY HIS ARG ARG GLU GLY ASN
SEQRES 7 A 289 ILE GLN TYR LEU PHE LEU GLU TYR CYS SER GLY GLY GLU
SEQRES 8 A 289 LEU PHE ASP ARG ILE GLU PRO ASP ILE GLY MET PRO GLU
SEQRES 9 A 289 PRO ASP ALA GLN ARG PHE PHE HIS GLN LEU MET ALA GLY
SEQRES 10 A 289 VAL VAL TYR LEU HIS GLY ILE GLY ILE THR HIS ARG ASP
SEQRES 11 A 289 ILE LYS PRO GLU ASN LEU LEU LEU ASP GLU ARG ASP ASN
SEQRES 12 A 289 LEU LYS ILE SER ASP PHE GLY LEU ALA THR VAL PHE ARG
SEQRES 13 A 289 TYR ASN ASN ARG GLU ARG LEU LEU ASN LYS MET CYS GLY
SEQRES 14 A 289 THR LEU PRO TYR VAL ALA PRO GLU LEU LEU LYS ARG ARG
SEQRES 15 A 289 GLU PHE HIS ALA GLU PRO VAL ASP VAL TRP SER CYS GLY
SEQRES 16 A 289 ILE VAL LEU THR ALA MET LEU ALA GLY GLU LEU PRO TRP
SEQRES 17 A 289 ASP GLN PRO SER ASP SER CYS GLN GLU TYR SER ASP TRP
SEQRES 18 A 289 LYS GLU LYS LYS THR TYR LEU ASN PRO TRP LYS LYS ILE
SEQRES 19 A 289 ASP SER ALA PRO LEU ALA LEU LEU HIS LYS ILE LEU VAL
SEQRES 20 A 289 GLU ASN PRO SER ALA ARG ILE THR ILE PRO ASP ILE LYS
SEQRES 21 A 289 LYS ASP ARG TRP TYR ASN LYS PRO LEU LYS LYS GLY ALA
SEQRES 22 A 289 LYS ARG PRO ARG VAL THR SER GLY GLY VAL SER GLU SER
SEQRES 23 A 289 PRO SER GLY
HET YM7 A1272 23
HET YM7 A1273 23
HET EDO A1274 4
HET EDO A1275 4
HET EDO A1276 4
HET EDO A1277 4
HETNAM YM7 5-({6-[(PIPERIDIN-4-YLMETHYL)AMINO]PYRIMIDIN-4-
HETNAM 2 YM7 YL}AMINO)PYRAZINE-2-CARBONITRILE
HETNAM EDO 1,2-ETHANEDIOL
HETSYN EDO ETHYLENE GLYCOL
FORMUL 2 YM7 2(C15 H18 N8)
FORMUL 4 EDO 4(C2 H6 O2)
FORMUL 8 HOH *248(H2 O)
HELIX 1 1 ASN A 51 LEU A 62 1 12
HELIX 2 2 PHE A 93 ILE A 96 5 4
HELIX 3 3 PRO A 103 ILE A 124 1 22
HELIX 4 4 LYS A 132 GLU A 134 5 3
HELIX 5 5 THR A 170 VAL A 174 5 5
HELIX 6 6 ALA A 175 ARG A 181 1 7
HELIX 7 7 HIS A 185 GLY A 204 1 20
HELIX 8 8 CYS A 215 GLU A 223 1 9
HELIX 9 9 PRO A 230 ILE A 234 5 5
HELIX 10 10 ASP A 235 LEU A 246 1 12
HELIX 11 11 THR A 255 LYS A 260 1 6
SHEET 1 AA 5 TRP A 9 THR A 14 0
SHEET 2 AA 5 VAL A 23 ASN A 28 -1 O LEU A 25 N VAL A 12
SHEET 3 AA 5 ALA A 34 VAL A 40 -1 O VAL A 35 N ALA A 26
SHEET 4 AA 5 GLN A 80 GLU A 85 -1 O GLN A 80 N VAL A 40
SHEET 5 AA 5 PHE A 70 ARG A 75 -1 N TYR A 71 O PHE A 83
SHEET 1 AB 3 GLY A 90 GLU A 91 0
SHEET 2 AB 3 LEU A 136 LEU A 138 -1 N LEU A 138 O GLY A 90
SHEET 3 AB 3 LEU A 144 ILE A 146 -1 O LYS A 145 N LEU A 137
SHEET 1 AC 2 ILE A 126 THR A 127 0
SHEET 2 AC 2 THR A 153 VAL A 154 -1 O THR A 153 N THR A 127
SHEET 1 AD 2 ARG A 156 TYR A 157 0
SHEET 2 AD 2 ARG A 160 GLU A 161 -1 O ARG A 160 N TYR A 157
CISPEP 1 ASN A 229 PRO A 230 0 1.88
SITE 1 AC1 15 LEU A 15 ALA A 36 LYS A 38 LEU A 84
SITE 2 AC1 15 GLU A 85 TYR A 86 CYS A 87 GLU A 91
SITE 3 AC1 15 GLU A 134 LEU A 137 SER A 147 ASP A 148
SITE 4 AC1 15 HOH A2005 HOH A2243 HOH A2244
SITE 1 AC2 6 TRP A 9 GLU A 33 ALA A 34 TYR A 71
SITE 2 AC2 6 ARG A 74 PHE A 83
SITE 1 AC3 3 ARG A 29 LEU A 163 GLU A 183
SITE 1 AC4 5 LYS A 132 GLU A 134 THR A 170 HOH A2050
SITE 2 AC4 5 HOH A2245
SITE 1 AC5 3 HIS A 243 LEU A 246 HOH A2221
SITE 1 AC6 2 HOH A2172 HOH A2246
CRYST1 44.940 65.710 57.940 90.00 94.14 90.00 P 1 21 1 2
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 0.022252 0.000000 0.001611 0.00000
SCALE2 0.000000 0.015218 0.000000 0.00000
SCALE3 0.000000 0.000000 0.017304 0.00000
(ATOM LINES ARE NOT SHOWN.)
END
