HEADER TRANSFERASE 29-OCT-15 5EI8
TITLE RAPID DISCOVERY OF PYRIDO[3,4-D]PYRIMIDINE INHIBITORS OF MONOPOLAR
TITLE 2 SPINDLE KINASE 1 (MPS1) USING A STRUCTURE-BASED HYDRIDIZATION
TITLE 3 APPROACH
COMPND MOL_ID: 1;
COMPND 2 MOLECULE: DUAL SPECIFICITY PROTEIN KINASE TTK;
COMPND 3 CHAIN: A;
COMPND 4 SYNONYM: PHOSPHOTYROSINE PICKED THREONINE-PROTEIN KINASE,PYT;
COMPND 5 EC: 2.7.12.1;
COMPND 6 ENGINEERED: YES;
COMPND 7 OTHER_DETAILS: N-[2-METHOXY-4-(1-METHYL-1H-PYRAZOL-4-YL)PHENYL]-8-(1-
COMPND 8 METHYL-1H-PYRAZOL-4-YL)PYRIDO[3,4-D]PYRIMIDIN-2-AMINE
SOURCE MOL_ID: 1;
SOURCE 2 ORGANISM_SCIENTIFIC: HOMO SAPIENS;
SOURCE 3 ORGANISM_COMMON: HUMAN;
SOURCE 4 ORGANISM_TAXID: 9606;
SOURCE 5 GENE: TTK, MPS1, MPS1L1;
SOURCE 6 EXPRESSION_SYSTEM: ESCHERICHIA COLI BL21;
SOURCE 7 EXPRESSION_SYSTEM_TAXID: 511693
KEYWDS SPINDLE ASSEMBLY CHECKPOINT (SAC), ONCOLOGY TARGET PYRIDO[3, 4-
KEYWDS 2 D]PYRIMIDINE BASED INHIBITORS SELECTIVE AGAINST MPS1, TRANSFERASE
EXPDTA X-RAY DIFFRACTION
AUTHOR P.INNOCENTI,H.L.WOODWARD,S.SOLANKI,N.NAUD,I.M.WESTWOOD,N.CRONIN,
AUTHOR 2 A.HAYES,J.ROBERTS,A.T.HENLEY,R.BAKER,A.FAISAL,G.MAK,G.BOX,M.VALENTI,
AUTHOR 3 A.DE HAVEN BRANDON,L.O'FEE,J.SAVILLE,J.SCHMITT,R.BURKE,R.L.M.VAN
AUTHOR 4 MONTFORT,F.I.RAYMAUD,S.A.ECCLES,S.LINARDOPOULOS,J.BLAGG,S.HOELDER
REVDAT 3 30-AUG-17 5EI8 1 REMARK
REVDAT 2 11-MAY-16 5EI8 1 JRNL
REVDAT 1 20-APR-16 5EI8 0
JRNL AUTH P.INNOCENTI,H.L.WOODWARD,S.SOLANKI,S.NAUD,I.M.WESTWOOD,
JRNL AUTH 2 N.CRONIN,A.HAYES,J.ROBERTS,A.T.HENLEY,R.BAKER,A.FAISAL,
JRNL AUTH 3 G.W.MAK,G.BOX,M.VALENTI,A.DE HAVEN BRANDON,L.O'FEE,
JRNL AUTH 4 H.SAVILLE,J.SCHMITT,B.MATIJSSEN,R.BURKE,R.L.VAN MONTFORT,
JRNL AUTH 5 F.I.RAYNAUD,S.A.ECCLES,S.LINARDOPOULOS,J.BLAGG,S.HOELDER
JRNL TITL RAPID DISCOVERY OF PYRIDO[3,4-D]PYRIMIDINE INHIBITORS OF
JRNL TITL 2 MONOPOLAR SPINDLE KINASE 1 (MPS1) USING A STRUCTURE-BASED
JRNL TITL 3 HYBRIDIZATION APPROACH.
JRNL REF J.MED.CHEM. V. 59 3671 2016
JRNL REFN ISSN 0022-2623
JRNL PMID 27055065
JRNL DOI 10.1021/ACS.JMEDCHEM.5B01811
REMARK 2
REMARK 2 RESOLUTION. 2.17 ANGSTROMS.
REMARK 3
REMARK 3 REFINEMENT.
REMARK 3 PROGRAM : BUSTER 2.10.2
REMARK 3 AUTHORS : BRICOGNE,BLANC,BRANDL,FLENSBURG,KELLER,
REMARK 3 : PACIOREK,ROVERSI,SHARFF,SMART,VONRHEIN,
REMARK 3 : WOMACK,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) : 37.53
REMARK 3 DATA CUTOFF (SIGMA(F)) : 0.000
REMARK 3 COMPLETENESS FOR RANGE (%) : 99.2
REMARK 3 NUMBER OF REFLECTIONS : 20909
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) : 0.216
REMARK 3 R VALUE (WORKING SET) : 0.214
REMARK 3 FREE R VALUE : 0.244
REMARK 3 FREE R VALUE TEST SET SIZE (%) : 5.220
REMARK 3 FREE R VALUE TEST SET COUNT : 1092
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 : NULL
REMARK 3 BIN RESOLUTION RANGE HIGH (ANGSTROMS) : 2.17
REMARK 3 BIN RESOLUTION RANGE LOW (ANGSTROMS) : 2.29
REMARK 3 BIN COMPLETENESS (WORKING+TEST) (%) : 99.93
REMARK 3 REFLECTIONS IN BIN (WORKING + TEST SET) : NULL
REMARK 3 BIN R VALUE (WORKING + TEST SET) : NULL
REMARK 3 REFLECTIONS IN BIN (WORKING SET) : 2604
REMARK 3 BIN R VALUE (WORKING SET) : 0.2240
REMARK 3 BIN FREE R VALUE : 0.2391
REMARK 3 BIN FREE R VALUE TEST SET SIZE (%) : 5.27
REMARK 3 BIN FREE R VALUE TEST SET COUNT : 145
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 : 2040
REMARK 3 NUCLEIC ACID ATOMS : 0
REMARK 3 HETEROGEN ATOMS : 43
REMARK 3 SOLVENT ATOMS : 40
REMARK 3
REMARK 3 B VALUES.
REMARK 3 FROM WILSON PLOT (A**2) : 41.97
REMARK 3 MEAN B VALUE (OVERALL, A**2) : 64.52
REMARK 3 OVERALL ANISOTROPIC B VALUE.
REMARK 3 B11 (A**2) : 5.22670
REMARK 3 B22 (A**2) : 3.43110
REMARK 3 B33 (A**2) : -8.65780
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) : 0.405
REMARK 3 DPI (BLOW EQ-10) BASED ON R VALUE (A) : 0.191
REMARK 3 DPI (BLOW EQ-9) BASED ON FREE R VALUE (A) : 0.167
REMARK 3 DPI (CRUICKSHANK) BASED ON R VALUE (A) : 0.193
REMARK 3 DPI (CRUICKSHANK) BASED ON FREE R VALUE (A) : 0.169
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 : 0.946
REMARK 3 CORRELATION COEFFICIENT FO-FC FREE : 0.939
REMARK 3
REMARK 3 NUMBER OF GEOMETRIC FUNCTION TERMS DEFINED : 15
REMARK 3 TERM COUNT WEIGHT FUNCTION.
REMARK 3 BOND LENGTHS : 2130 ; 2.000 ; HARMONIC
REMARK 3 BOND ANGLES : 2894 ; 2.000 ; HARMONIC
REMARK 3 TORSION ANGLES : 704 ; 2.000 ; SINUSOIDAL
REMARK 3 TRIGONAL CARBON PLANES : 52 ; 2.000 ; HARMONIC
REMARK 3 GENERAL PLANES : 333 ; 5.000 ; HARMONIC
REMARK 3 ISOTROPIC THERMAL FACTORS : 2130 ; 20.000 ; HARMONIC
REMARK 3 BAD NON-BONDED CONTACTS : NULL ; NULL ; NULL
REMARK 3 IMPROPER TORSIONS : NULL ; NULL ; NULL
REMARK 3 PSEUDOROTATION ANGLES : NULL ; NULL ; NULL
REMARK 3 CHIRAL IMPROPER TORSION : 286 ; 5.000 ; SEMIHARMONIC
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 : 2419 ; 4.000 ; SEMIHARMONIC
REMARK 3
REMARK 3 RMS DEVIATIONS FROM IDEAL VALUES.
REMARK 3 BOND LENGTHS (A) : 0.010
REMARK 3 BOND ANGLES (DEGREES) : 1.09
REMARK 3 PEPTIDE OMEGA TORSION ANGLES (DEGREES) : 2.95
REMARK 3 OTHER TORSION ANGLES (DEGREES) : 19.60
REMARK 3
REMARK 3 TLS DETAILS
REMARK 3 NUMBER OF TLS GROUPS : 8
REMARK 3
REMARK 3 TLS GROUP : 1
REMARK 3 SELECTION: {A|516 - 561}
REMARK 3 ORIGIN FOR THE GROUP (A): 10.3827 -30.2962 -7.5730
REMARK 3 T TENSOR
REMARK 3 T11: -0.1386 T22: 0.1497
REMARK 3 T33: -0.2853 T12: -0.0396
REMARK 3 T13: -0.0453 T23: 0.1514
REMARK 3 L TENSOR
REMARK 3 L11: 8.3155 L22: 7.8239
REMARK 3 L33: 7.8355 L12: 2.7143
REMARK 3 L13: -2.6261 L23: -0.7499
REMARK 3 S TENSOR
REMARK 3 S11: -0.0737 S12: -0.5442 S13: -0.2124
REMARK 3 S21: 0.5437 S22: -0.0232 S23: -0.4511
REMARK 3 S31: -0.0196 S32: 0.0532 S33: 0.0969
REMARK 3
REMARK 3 TLS GROUP : 2
REMARK 3 SELECTION: {A|562 - 580}
REMARK 3 ORIGIN FOR THE GROUP (A): 8.7834 -27.8700 -24.9652
REMARK 3 T TENSOR
REMARK 3 T11: -0.3040 T22: 0.3040
REMARK 3 T33: -0.0492 T12: -0.1292
REMARK 3 T13: 0.0122 T23: 0.1520
REMARK 3 L TENSOR
REMARK 3 L11: 5.4927 L22: 1.3288
REMARK 3 L33: 5.3633 L12: 0.7787
REMARK 3 L13: 2.8022 L23: -0.6466
REMARK 3 S TENSOR
REMARK 3 S11: 0.0038 S12: 0.3161 S13: -0.2570
REMARK 3 S21: -0.0620 S22: 0.1699 S23: -0.1226
REMARK 3 S31: -0.1051 S32: -0.1106 S33: -0.1737
REMARK 3
REMARK 3 TLS GROUP : 3
REMARK 3 SELECTION: {A|581 - 620}
REMARK 3 ORIGIN FOR THE GROUP (A): 0.4192 -30.7919 -14.0803
REMARK 3 T TENSOR
REMARK 3 T11: -0.1221 T22: 0.2784
REMARK 3 T33: -0.2687 T12: -0.0198
REMARK 3 T13: 0.0793 T23: 0.1402
REMARK 3 L TENSOR
REMARK 3 L11: 8.2273 L22: 2.9890
REMARK 3 L33: 2.9750 L12: 1.2473
REMARK 3 L13: 2.9104 L23: -0.3763
REMARK 3 S TENSOR
REMARK 3 S11: 0.0716 S12: -0.1130 S13: 0.2900
REMARK 3 S21: 0.2195 S22: 0.0673 S23: -0.0530
REMARK 3 S31: -0.2167 S32: -0.5017 S33: -0.1389
REMARK 3
REMARK 3 TLS GROUP : 4
REMARK 3 SELECTION: {A|621 - 641}
REMARK 3 ORIGIN FOR THE GROUP (A): -13.0317 -30.3928 -22.6143
REMARK 3 T TENSOR
REMARK 3 T11: -0.3040 T22: 0.2802
REMARK 3 T33: -0.1274 T12: 0.0779
REMARK 3 T13: -0.0286 T23: 0.1520
REMARK 3 L TENSOR
REMARK 3 L11: 7.2371 L22: 5.2703
REMARK 3 L33: 5.9138 L12: 1.7674
REMARK 3 L13: 2.1083 L23: -1.3399
REMARK 3 S TENSOR
REMARK 3 S11: -0.0009 S12: 0.1609 S13: 0.0920
REMARK 3 S21: -0.1431 S22: -0.1934 S23: 0.1681
REMARK 3 S31: -0.2562 S32: 0.0448 S33: 0.1943
REMARK 3
REMARK 3 TLS GROUP : 5
REMARK 3 SELECTION: {A|642 - 691}
REMARK 3 ORIGIN FOR THE GROUP (A): -2.0653 -37.6187 -21.1294
REMARK 3 T TENSOR
REMARK 3 T11: -0.3040 T22: 0.3040
REMARK 3 T33: -0.2803 T12: -0.0302
REMARK 3 T13: 0.0030 T23: 0.1520
REMARK 3 L TENSOR
REMARK 3 L11: 8.0722 L22: 4.4326
REMARK 3 L33: 5.1731 L12: 1.0101
REMARK 3 L13: 1.4290 L23: 0.6194
REMARK 3 S TENSOR
REMARK 3 S11: 0.1879 S12: 0.2724 S13: -0.2832
REMARK 3 S21: 0.2156 S22: 0.0037 S23: -0.1152
REMARK 3 S31: 0.0070 S32: 0.0399 S33: -0.1916
REMARK 3
REMARK 3 TLS GROUP : 6
REMARK 3 SELECTION: {A|692 - 729}
REMARK 3 ORIGIN FOR THE GROUP (A): -9.5030 -42.0434 -31.2203
REMARK 3 T TENSOR
REMARK 3 T11: -0.3040 T22: 0.3040
REMARK 3 T33: -0.2904 T12: -0.0278
REMARK 3 T13: -0.0259 T23: 0.1008
REMARK 3 L TENSOR
REMARK 3 L11: 1.0849 L22: 6.0132
REMARK 3 L33: 0.0000 L12: -0.7439
REMARK 3 L13: 2.2683 L23: -1.6590
REMARK 3 S TENSOR
REMARK 3 S11: 0.0240 S12: 0.1345 S13: -0.3922
REMARK 3 S21: -0.2861 S22: 0.0077 S23: 0.0692
REMARK 3 S31: 0.2546 S32: 0.0275 S33: -0.0317
REMARK 3
REMARK 3 TLS GROUP : 7
REMARK 3 SELECTION: {A|730 - 761}
REMARK 3 ORIGIN FOR THE GROUP (A): -13.8837 -52.2022 -29.5712
REMARK 3 T TENSOR
REMARK 3 T11: -0.2399 T22: 0.2889
REMARK 3 T33: -0.1478 T12: -0.1236
REMARK 3 T13: -0.0391 T23: 0.0769
REMARK 3 L TENSOR
REMARK 3 L11: 4.7947 L22: 4.2683
REMARK 3 L33: 1.3680 L12: -1.5986
REMARK 3 L13: 1.0624 L23: -0.5762
REMARK 3 S TENSOR
REMARK 3 S11: -0.0344 S12: 0.1119 S13: -0.2270
REMARK 3 S21: -0.1736 S22: 0.1811 S23: 0.4597
REMARK 3 S31: 0.5365 S32: -0.0304 S33: -0.1467
REMARK 3
REMARK 3 TLS GROUP : 8
REMARK 3 SELECTION: {A|762 - 794}
REMARK 3 ORIGIN FOR THE GROUP (A): -19.7007 -35.8088 -31.3368
REMARK 3 T TENSOR
REMARK 3 T11: -0.3040 T22: 0.3040
REMARK 3 T33: -0.1469 T12: -0.0183
REMARK 3 T13: -0.0690 T23: 0.1520
REMARK 3 L TENSOR
REMARK 3 L11: 4.8598 L22: 4.8641
REMARK 3 L33: 0.0000 L12: -2.0641
REMARK 3 L13: 2.9104 L23: -2.8690
REMARK 3 S TENSOR
REMARK 3 S11: -0.0132 S12: 0.4162 S13: -0.1170
REMARK 3 S21: -0.2093 S22: 0.1307 S23: 0.5182
REMARK 3 S31: 0.1571 S32: -0.2655 S33: -0.1174
REMARK 3
REMARK 3 OTHER REFINEMENT REMARKS: NULL
REMARK 4
REMARK 4 5EI8 COMPLIES WITH FORMAT V. 3.30, 13-JUL-11
REMARK 100
REMARK 100 THIS ENTRY HAS BEEN PROCESSED BY PDBE ON 29-OCT-15.
REMARK 100 THE DEPOSITION ID IS D_1000214957.
REMARK 200
REMARK 200 EXPERIMENTAL DETAILS
REMARK 200 EXPERIMENT TYPE : X-RAY DIFFRACTION
REMARK 200 DATE OF DATA COLLECTION : 16-MAR-15
REMARK 200 TEMPERATURE (KELVIN) : 100
REMARK 200 PH : 7.5
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-X
REMARK 200 MONOCHROMATIC OR LAUE (M/L) : M
REMARK 200 WAVELENGTH OR RANGE (A) : 1.54
REMARK 200 MONOCHROMATOR : NULL
REMARK 200 OPTICS : NULL
REMARK 200
REMARK 200 DETECTOR TYPE : PIXEL
REMARK 200 DETECTOR MANUFACTURER : DECTRIS PILATUS 300K
REMARK 200 INTENSITY-INTEGRATION SOFTWARE : XDS
REMARK 200 DATA SCALING SOFTWARE : AIMLESS
REMARK 200
REMARK 200 NUMBER OF UNIQUE REFLECTIONS : 21262
REMARK 200 RESOLUTION RANGE HIGH (A) : 2.170
REMARK 200 RESOLUTION RANGE LOW (A) : 39.980
REMARK 200 REJECTION CRITERIA (SIGMA(I)) : NULL
REMARK 200
REMARK 200 OVERALL.
REMARK 200 COMPLETENESS FOR RANGE (%) : 99.6
REMARK 200 DATA REDUNDANCY : 21.60
REMARK 200 R MERGE (I) : NULL
REMARK 200 R SYM (I) : NULL
REMARK 200 <I/SIGMA(I)> FOR THE DATA SET : 8.9000
REMARK 200
REMARK 200 IN THE HIGHEST RESOLUTION SHELL.
REMARK 200 HIGHEST RESOLUTION SHELL, RANGE HIGH (A) : NULL
REMARK 200 HIGHEST RESOLUTION SHELL, RANGE LOW (A) : NULL
REMARK 200 COMPLETENESS FOR SHELL (%) : NULL
REMARK 200 DATA REDUNDANCY IN SHELL : NULL
REMARK 200 R MERGE FOR SHELL (I) : NULL
REMARK 200 R SYM FOR SHELL (I) : NULL
REMARK 200 <I/SIGMA(I)> FOR SHELL : NULL
REMARK 200
REMARK 200 DIFFRACTION PROTOCOL: SINGLE WAVELENGTH
REMARK 200 METHOD USED TO DETERMINE THE STRUCTURE: NULL
REMARK 200 SOFTWARE USED: PHASER
REMARK 200 STARTING MODEL: NULL
REMARK 200
REMARK 200 REMARK: NULL
REMARK 280
REMARK 280 CRYSTAL
REMARK 280 SOLVENT CONTENT, VS (%): 55.10
REMARK 280 MATTHEWS COEFFICIENT, VM (ANGSTROMS**3/DA): 2.77
REMARK 280
REMARK 280 CRYSTALLIZATION CONDITIONS: 0.1 M BIS-TRIS PROPANE 0.2 M NGCL2 0.2
REMARK 280 M SODIUM FORMATE 20 % PEG3350, PH 7.5, VAPOR DIFFUSION, SITTING
REMARK 280 DROP, TEMPERATURE 291.15K
REMARK 290
REMARK 290 CRYSTALLOGRAPHIC SYMMETRY
REMARK 290 SYMMETRY OPERATORS FOR SPACE GROUP: I 2 2 2
REMARK 290
REMARK 290 SYMOP SYMMETRY
REMARK 290 NNNMMM OPERATOR
REMARK 290 1555 X,Y,Z
REMARK 290 2555 -X,-Y,Z
REMARK 290 3555 -X,Y,-Z
REMARK 290 4555 X,-Y,-Z
REMARK 290 5555 X+1/2,Y+1/2,Z+1/2
REMARK 290 6555 -X+1/2,-Y+1/2,Z+1/2
REMARK 290 7555 -X+1/2,Y+1/2,-Z+1/2
REMARK 290 8555 X+1/2,-Y+1/2,-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 0.00000
REMARK 290 SMTRY1 3 -1.000000 0.000000 0.000000 0.00000
REMARK 290 SMTRY2 3 0.000000 1.000000 0.000000 0.00000
REMARK 290 SMTRY3 3 0.000000 0.000000 -1.000000 0.00000
REMARK 290 SMTRY1 4 1.000000 0.000000 0.000000 0.00000
REMARK 290 SMTRY2 4 0.000000 -1.000000 0.000000 0.00000
REMARK 290 SMTRY3 4 0.000000 0.000000 -1.000000 0.00000
REMARK 290 SMTRY1 5 1.000000 0.000000 0.000000 35.00150
REMARK 290 SMTRY2 5 0.000000 1.000000 0.000000 50.99150
REMARK 290 SMTRY3 5 0.000000 0.000000 1.000000 55.43400
REMARK 290 SMTRY1 6 -1.000000 0.000000 0.000000 35.00150
REMARK 290 SMTRY2 6 0.000000 -1.000000 0.000000 50.99150
REMARK 290 SMTRY3 6 0.000000 0.000000 1.000000 55.43400
REMARK 290 SMTRY1 7 -1.000000 0.000000 0.000000 35.00150
REMARK 290 SMTRY2 7 0.000000 1.000000 0.000000 50.99150
REMARK 290 SMTRY3 7 0.000000 0.000000 -1.000000 55.43400
REMARK 290 SMTRY1 8 1.000000 0.000000 0.000000 35.00150
REMARK 290 SMTRY2 8 0.000000 -1.000000 0.000000 50.99150
REMARK 290 SMTRY3 8 0.000000 0.000000 -1.000000 55.43400
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 SOFTWARE DETERMINED QUATERNARY STRUCTURE: MONOMERIC
REMARK 350 SOFTWARE USED: PISA
REMARK 350 TOTAL BURIED SURFACE AREA: 650 ANGSTROM**2
REMARK 350 SURFACE AREA OF THE COMPLEX: 12370 ANGSTROM**2
REMARK 350 CHANGE IN SOLVENT FREE ENERGY: 6.0 KCAL/MOL
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 496
REMARK 465 HIS A 497
REMARK 465 HIS A 498
REMARK 465 HIS A 499
REMARK 465 HIS A 500
REMARK 465 HIS A 501
REMARK 465 HIS A 502
REMARK 465 SER A 503
REMARK 465 SER A 504
REMARK 465 GLY A 505
REMARK 465 VAL A 506
REMARK 465 ASP A 507
REMARK 465 LEU A 508
REMARK 465 GLY A 509
REMARK 465 THR A 510
REMARK 465 GLU A 511
REMARK 465 ASN A 512
REMARK 465 LEU A 513
REMARK 465 TYR A 514
REMARK 465 PHE A 515
REMARK 465 THR A 675
REMARK 465 THR A 676
REMARK 465 SER A 677
REMARK 465 VAL A 678
REMARK 465 VAL A 679
REMARK 465 LYS A 680
REMARK 465 ASP A 681
REMARK 465 SER A 682
REMARK 465 GLN A 683
REMARK 465 SER A 699
REMARK 465 SER A 700
REMARK 465 SER A 701
REMARK 465 ARG A 702
REMARK 465 GLU A 703
REMARK 465 ASN A 704
REMARK 465 GLY A 705
REMARK 465 LYS A 706
REMARK 465 SER A 707
REMARK 465 LYS A 708
REMARK 465 HIS A 796
REMARK 465 PRO A 797
REMARK 465 VAL A 798
REMARK 465 ASN A 799
REMARK 465 GLN A 800
REMARK 465 MET A 801
REMARK 465 ALA A 802
REMARK 465 LYS A 803
REMARK 465 GLY A 804
REMARK 465 THR A 805
REMARK 465 THR A 806
REMARK 465 GLU A 807
REMARK 465 GLU A 808
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 GLN A 516 CG CD OE1 NE2
REMARK 470 ARG A 523 CD NE CZ NH1 NH2
REMARK 470 LYS A 529 NZ
REMARK 470 LYS A 538 CE NZ
REMARK 470 GLU A 545 CG CD OE1 OE2
REMARK 470 LYS A 546 CG CD CE NZ
REMARK 470 GLU A 559 CG CD OE1 OE2
REMARK 470 GLN A 563 CG CD OE1 NE2
REMARK 470 LYS A 577 CE NZ
REMARK 470 GLN A 580 CD OE1 NE2
REMARK 470 GLN A 596 CD OE1 NE2
REMARK 470 LYS A 614 CE NZ
REMARK 470 LYS A 615 CE NZ
REMARK 470 LYS A 616 CE NZ
REMARK 470 LYS A 617 CG CD CE NZ
REMARK 470 SER A 618 OG
REMARK 470 LYS A 629 CG CD CE NZ
REMARK 470 ASP A 657 CG OD1 OD2
REMARK 470 VAL A 684 CG1 CG2
REMARK 470 LYS A 710 CG CD CE NZ
REMARK 470 GLU A 753 CG CD OE1 OE2
REMARK 470 GLU A 755 CG CD OE1 OE2
REMARK 470 LYS A 762 CG CD CE NZ
REMARK 470 LYS A 769 CG CD CE NZ
REMARK 470 LYS A 773 CD CE NZ
REMARK 470 LYS A 777 CG CD CE NZ
REMARK 470 GLN A 794 CG CD OE1 NE2
REMARK 470 THR A 795 OG1 CG2
REMARK 500
REMARK 500 GEOMETRY AND STEREOCHEMISTRY
REMARK 500 SUBTOPIC: CLOSE CONTACTS IN SAME ASYMMETRIC UNIT
REMARK 500
REMARK 500 THE FOLLOWING ATOMS ARE IN CLOSE CONTACT.
REMARK 500
REMARK 500 ATM1 RES C SSEQI ATM2 RES C SSEQI DISTANCE
REMARK 500 NE2 GLN A 530 OD2 ASP A 674 2.15
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 SER A 646 -3.86 71.71
REMARK 500 ILE A 667 -62.91 -100.46
REMARK 500 LEU A 772 38.82 -99.63
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 5OE A 901
REMARK 800
REMARK 800 SITE_IDENTIFIER: AC2
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: binding site for residue DMS A 902
REMARK 800
REMARK 800 SITE_IDENTIFIER: AC3
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: binding site for residue DMS A 903
REMARK 800
REMARK 800 SITE_IDENTIFIER: AC4
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: binding site for residue DMS A 904
REMARK 900
REMARK 900 RELATED ENTRIES
REMARK 900 RELATED ID: 5EH0 RELATED DB: PDB
REMARK 900 5EH0 CONTAINS THE SAMPLE PROTEIN MPS1 COMPLEXED WITH N2-(2-METHOXY-
REMARK 900 4-(1-METHYL-1H-PYRAZOL-4-YL)PHENYL)-N8-NEOPENTYLPYRIDO[3,4-D]
REMARK 900 PYRIMIDINE-2,8-DIAMINE
DBREF 5EI8 A 519 753 UNP P33981 TTK_HUMAN 519 753
SEQADV 5EI8 MET A 496 UNP P33981 INITIATING METHIONINE
SEQADV 5EI8 HIS A 497 UNP P33981 EXPRESSION TAG
SEQADV 5EI8 HIS A 498 UNP P33981 EXPRESSION TAG
SEQADV 5EI8 HIS A 499 UNP P33981 EXPRESSION TAG
SEQADV 5EI8 HIS A 500 UNP P33981 EXPRESSION TAG
SEQADV 5EI8 HIS A 501 UNP P33981 EXPRESSION TAG
SEQADV 5EI8 HIS A 502 UNP P33981 EXPRESSION TAG
SEQADV 5EI8 SER A 503 UNP P33981 EXPRESSION TAG
SEQADV 5EI8 SER A 504 UNP P33981 EXPRESSION TAG
SEQADV 5EI8 GLY A 505 UNP P33981 EXPRESSION TAG
SEQADV 5EI8 VAL A 506 UNP P33981 EXPRESSION TAG
SEQADV 5EI8 ASP A 507 UNP P33981 EXPRESSION TAG
SEQADV 5EI8 LEU A 508 UNP P33981 EXPRESSION TAG
SEQADV 5EI8 GLY A 509 UNP P33981 EXPRESSION TAG
SEQADV 5EI8 THR A 510 UNP P33981 EXPRESSION TAG
SEQADV 5EI8 GLU A 511 UNP P33981 EXPRESSION TAG
SEQADV 5EI8 ASN A 512 UNP P33981 EXPRESSION TAG
SEQADV 5EI8 LEU A 513 UNP P33981 EXPRESSION TAG
SEQADV 5EI8 TYR A 514 UNP P33981 EXPRESSION TAG
SEQADV 5EI8 PHE A 515 UNP P33981 EXPRESSION TAG
SEQADV 5EI8 GLN A 516 UNP P33981 EXPRESSION TAG
SEQADV 5EI8 SER A 517 UNP P33981 EXPRESSION TAG
SEQADV 5EI8 MET A 518 UNP P33981 EXPRESSION TAG
SEQADV 5EI8 ILE A 754 UNP P33981 EXPRESSION TAG
SEQADV 5EI8 GLU A 755 UNP P33981 EXPRESSION TAG
SEQADV 5EI8 PHE A 756 UNP P33981 EXPRESSION TAG
SEQADV 5EI8 PRO A 757 UNP P33981 EXPRESSION TAG
SEQADV 5EI8 ASP A 758 UNP P33981 EXPRESSION TAG
SEQADV 5EI8 ILE A 759 UNP P33981 EXPRESSION TAG
SEQADV 5EI8 PRO A 760 UNP P33981 EXPRESSION TAG
SEQADV 5EI8 GLU A 761 UNP P33981 EXPRESSION TAG
SEQADV 5EI8 LYS A 762 UNP P33981 EXPRESSION TAG
SEQADV 5EI8 ASP A 763 UNP P33981 EXPRESSION TAG
SEQADV 5EI8 LEU A 764 UNP P33981 EXPRESSION TAG
SEQADV 5EI8 GLN A 765 UNP P33981 EXPRESSION TAG
SEQADV 5EI8 ASP A 766 UNP P33981 EXPRESSION TAG
SEQADV 5EI8 VAL A 767 UNP P33981 EXPRESSION TAG
SEQADV 5EI8 LEU A 768 UNP P33981 EXPRESSION TAG
SEQADV 5EI8 LYS A 769 UNP P33981 EXPRESSION TAG
SEQADV 5EI8 CYS A 770 UNP P33981 EXPRESSION TAG
SEQADV 5EI8 CYS A 771 UNP P33981 EXPRESSION TAG
SEQADV 5EI8 LEU A 772 UNP P33981 EXPRESSION TAG
SEQADV 5EI8 LYS A 773 UNP P33981 EXPRESSION TAG
SEQADV 5EI8 ARG A 774 UNP P33981 EXPRESSION TAG
SEQADV 5EI8 ASP A 775 UNP P33981 EXPRESSION TAG
SEQADV 5EI8 PRO A 776 UNP P33981 EXPRESSION TAG
SEQADV 5EI8 LYS A 777 UNP P33981 EXPRESSION TAG
SEQADV 5EI8 GLN A 778 UNP P33981 EXPRESSION TAG
SEQADV 5EI8 ARG A 779 UNP P33981 EXPRESSION TAG
SEQADV 5EI8 ILE A 780 UNP P33981 EXPRESSION TAG
SEQADV 5EI8 SER A 781 UNP P33981 EXPRESSION TAG
SEQADV 5EI8 ILE A 782 UNP P33981 EXPRESSION TAG
SEQADV 5EI8 PRO A 783 UNP P33981 EXPRESSION TAG
SEQADV 5EI8 GLU A 784 UNP P33981 EXPRESSION TAG
SEQADV 5EI8 LEU A 785 UNP P33981 EXPRESSION TAG
SEQADV 5EI8 LEU A 786 UNP P33981 EXPRESSION TAG
SEQADV 5EI8 ALA A 787 UNP P33981 EXPRESSION TAG
SEQADV 5EI8 HIS A 788 UNP P33981 EXPRESSION TAG
SEQADV 5EI8 PRO A 789 UNP P33981 EXPRESSION TAG
SEQADV 5EI8 TYR A 790 UNP P33981 EXPRESSION TAG
SEQADV 5EI8 VAL A 791 UNP P33981 EXPRESSION TAG
SEQADV 5EI8 GLN A 792 UNP P33981 EXPRESSION TAG
SEQADV 5EI8 ILE A 793 UNP P33981 EXPRESSION TAG
SEQADV 5EI8 GLN A 794 UNP P33981 EXPRESSION TAG
SEQADV 5EI8 THR A 795 UNP P33981 EXPRESSION TAG
SEQADV 5EI8 HIS A 796 UNP P33981 EXPRESSION TAG
SEQADV 5EI8 PRO A 797 UNP P33981 EXPRESSION TAG
SEQADV 5EI8 VAL A 798 UNP P33981 EXPRESSION TAG
SEQADV 5EI8 ASN A 799 UNP P33981 EXPRESSION TAG
SEQADV 5EI8 GLN A 800 UNP P33981 EXPRESSION TAG
SEQADV 5EI8 MET A 801 UNP P33981 EXPRESSION TAG
SEQADV 5EI8 ALA A 802 UNP P33981 EXPRESSION TAG
SEQADV 5EI8 LYS A 803 UNP P33981 EXPRESSION TAG
SEQADV 5EI8 GLY A 804 UNP P33981 EXPRESSION TAG
SEQADV 5EI8 THR A 805 UNP P33981 EXPRESSION TAG
SEQADV 5EI8 THR A 806 UNP P33981 EXPRESSION TAG
SEQADV 5EI8 GLU A 807 UNP P33981 EXPRESSION TAG
SEQADV 5EI8 GLU A 808 UNP P33981 EXPRESSION TAG
SEQRES 1 A 313 MET HIS HIS HIS HIS HIS HIS SER SER GLY VAL ASP LEU
SEQRES 2 A 313 GLY THR GLU ASN LEU TYR PHE GLN SER MET SER VAL LYS
SEQRES 3 A 313 GLY ARG ILE TYR SER ILE LEU LYS GLN ILE GLY SER GLY
SEQRES 4 A 313 GLY SER SER LYS VAL PHE GLN VAL LEU ASN GLU LYS LYS
SEQRES 5 A 313 GLN ILE TYR ALA ILE LYS TYR VAL ASN LEU GLU GLU ALA
SEQRES 6 A 313 ASP ASN GLN THR LEU ASP SER TYR ARG ASN GLU ILE ALA
SEQRES 7 A 313 TYR LEU ASN LYS LEU GLN GLN HIS SER ASP LYS ILE ILE
SEQRES 8 A 313 ARG LEU TYR ASP TYR GLU ILE THR ASP GLN TYR ILE TYR
SEQRES 9 A 313 MET VAL MET GLU CYS GLY ASN ILE ASP LEU ASN SER TRP
SEQRES 10 A 313 LEU LYS LYS LYS LYS SER ILE ASP PRO TRP GLU ARG LYS
SEQRES 11 A 313 SER TYR TRP LYS ASN MET LEU GLU ALA VAL HIS THR ILE
SEQRES 12 A 313 HIS GLN HIS GLY ILE VAL HIS SER ASP LEU LYS PRO ALA
SEQRES 13 A 313 ASN PHE LEU ILE VAL ASP GLY MET LEU LYS LEU ILE ASP
SEQRES 14 A 313 PHE GLY ILE ALA ASN GLN MET GLN PRO ASP THR THR SER
SEQRES 15 A 313 VAL VAL LYS ASP SER GLN VAL GLY THR VAL ASN TYR MET
SEQRES 16 A 313 PRO PRO GLU ALA ILE LYS ASP MET SER SER SER ARG GLU
SEQRES 17 A 313 ASN GLY LYS SER LYS SER LYS ILE SER PRO LYS SER ASP
SEQRES 18 A 313 VAL TRP SER LEU GLY CYS ILE LEU TYR TYR MET THR TYR
SEQRES 19 A 313 GLY LYS THR PRO PHE GLN GLN ILE ILE ASN GLN ILE SER
SEQRES 20 A 313 LYS LEU HIS ALA ILE ILE ASP PRO ASN HIS GLU ILE GLU
SEQRES 21 A 313 PHE PRO ASP ILE PRO GLU LYS ASP LEU GLN ASP VAL LEU
SEQRES 22 A 313 LYS CYS CYS LEU LYS ARG ASP PRO LYS GLN ARG ILE SER
SEQRES 23 A 313 ILE PRO GLU LEU LEU ALA HIS PRO TYR VAL GLN ILE GLN
SEQRES 24 A 313 THR HIS PRO VAL ASN GLN MET ALA LYS GLY THR THR GLU
SEQRES 25 A 313 GLU
HET 5OE A 901 31
HET DMS A 902 4
HET DMS A 903 4
HET DMS A 904 4
HETNAM 5OE ~{N}-[2-METHOXY-4-(1-METHYLPYRAZOL-4-YL)PHENYL]-8-(1-
HETNAM 2 5OE METHYLPYRAZOL-4-YL)PYRIDO[3,4-D]PYRIMIDIN-2-AMINE
HETNAM DMS DIMETHYL SULFOXIDE
FORMUL 2 5OE C22 H20 N8 O
FORMUL 3 DMS 3(C2 H6 O S)
FORMUL 6 HOH *40(H2 O)
HELIX 1 AA1 ASP A 561 GLN A 579 1 19
HELIX 2 AA2 LEU A 609 LYS A 616 1 8
HELIX 3 AA3 ASP A 620 HIS A 641 1 22
HELIX 4 AA4 LYS A 649 ALA A 651 5 3
HELIX 5 AA5 PRO A 691 ASP A 697 1 7
HELIX 6 AA6 SER A 712 GLY A 730 1 19
HELIX 7 AA7 ASN A 739 ILE A 748 1 10
HELIX 8 AA8 GLU A 761 LEU A 772 1 12
HELIX 9 AA9 SER A 781 LEU A 786 1 6
HELIX 10 AB1 HIS A 788 ILE A 793 1 6
SHEET 1 AA1 6 SER A 517 VAL A 520 0
SHEET 2 AA1 6 ARG A 523 GLY A 534 -1 O ARG A 523 N VAL A 520
SHEET 3 AA1 6 SER A 537 LEU A 543 -1 O GLN A 541 N LYS A 529
SHEET 4 AA1 6 ILE A 549 ASN A 556 -1 O TYR A 554 N LYS A 538
SHEET 5 AA1 6 TYR A 597 MET A 602 -1 O MET A 602 N ALA A 551
SHEET 6 AA1 6 LEU A 588 ILE A 593 -1 N GLU A 592 O TYR A 599
SHEET 1 AA2 3 SER A 517 VAL A 520 0
SHEET 2 AA2 3 ARG A 523 GLY A 534 -1 O ARG A 523 N VAL A 520
SHEET 3 AA2 3 GLN A 672 PRO A 673 -1 O GLN A 672 N SER A 533
SHEET 1 AA3 3 ILE A 607 ASP A 608 0
SHEET 2 AA3 3 PHE A 653 ILE A 655 -1 O ILE A 655 N ILE A 607
SHEET 3 AA3 3 LEU A 660 LEU A 662 -1 O LYS A 661 N LEU A 654
SITE 1 AC1 12 ILE A 531 ALA A 551 ILE A 586 MET A 602
SITE 2 AC1 12 GLU A 603 CYS A 604 GLY A 605 ASN A 606
SITE 3 AC1 12 ASP A 608 SER A 611 LEU A 654 PRO A 673
SITE 1 AC2 1 TYR A 599
SITE 1 AC3 1 TYR A 550
SITE 1 AC4 5 LYS A 547 GLN A 548 ILE A 549 TYR A 550
SITE 2 AC4 5 TYR A 589
CRYST1 70.003 101.983 110.868 90.00 90.00 90.00 I 2 2 2 8
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 0.014285 0.000000 0.000000 0.00000
SCALE2 0.000000 0.009806 0.000000 0.00000
SCALE3 0.000000 0.000000 0.009020 0.00000
(ATOM LINES ARE NOT SHOWN.)
END
