HEADER TRANSFERASE 05-SEP-13 4C4H
TITLE STRUCTURE-BASED DESIGN OF ORALLY BIOAVAILABLE PYRROLOPYRIDINE
TITLE 2 INHIBITORS OF THE MITOTIC KINASE MPS1
COMPND MOL_ID: 1;
COMPND 2 MOLECULE: DUAL SPECIFICITY PROTEIN KINASE TTK;
COMPND 3 CHAIN: A;
COMPND 4 FRAGMENT: KINASE DOMAIN, RESIDUES 519-808;
COMPND 5 SYNONYM: 2.7.12.1, PHOSPHOTYROSINE PICKED THREONINE-PROTEIN KINASE,
COMPND 6 PYT, MONOPOLAR SPINDLE KINASE 1, MPS1;
COMPND 7 EC: 2.7.12.1;
COMPND 8 ENGINEERED: YES
SOURCE MOL_ID: 1;
SOURCE 2 ORGANISM_SCIENTIFIC: HOMO SAPIENS;
SOURCE 3 ORGANISM_COMMON: HUMAN;
SOURCE 4 ORGANISM_TAXID: 9606;
SOURCE 5 EXPRESSION_SYSTEM: ESCHERICHIA COLI;
SOURCE 6 EXPRESSION_SYSTEM_TAXID: 469008;
SOURCE 7 EXPRESSION_SYSTEM_STRAIN: BL21(DE3);
SOURCE 8 EXPRESSION_SYSTEM_VARIANT: A1
KEYWDS TRANSFERASE, PROTEIN KINASE, MITOSIS, STRUCTURE-BASED DESIGN
EXPDTA X-RAY DIFFRACTION
AUTHOR S.NAUD,I.M.WESTWOOD,A.FAISAL,P.SHELDRAKE,V.BAVETSIAS,B.ATRASH,M.LIU,
AUTHOR 2 A.HAYES,J.SCHMITT,A.WOOD,V.CHOI,K.BOXALL,G.MAK,M.GURDEN,M.VALENTI,
AUTHOR 3 A.DE HAVEN BRANDON,A.HENLEY,R.BAKER,C.MCANDREW,B.MATIJSSEN,R.BURKE,
AUTHOR 4 S.A.ECCLES,F.I.RAYNAUD,S.LINARDOPOULOS,R.VAN MONTFORT,J.BLAGG
REVDAT 3 20-DEC-23 4C4H 1 REMARK
REVDAT 2 15-JAN-14 4C4H 1 JRNL
REVDAT 1 04-DEC-13 4C4H 0
JRNL AUTH S.NAUD,I.M.WESTWOOD,A.FAISAL,P.W.SHELDRAKE,V.BAVETSIAS,
JRNL AUTH 2 B.ATRASH,K.J.CHEUNG,M.LIU,A.HAYES,J.SCHMITT,A.WOOD,V.CHOI,
JRNL AUTH 3 K.BOXALL,G.MAK,M.GURDEN,M.VALENTI,A.DE-HAVEN-BRANDON,
JRNL AUTH 4 A.HENLEY,R.BAKER,C.MCANDREW,B.MATIJSSEN,R.BURKE,S.HOELDER,
JRNL AUTH 5 S.A.ECCLES,F.I.RAYNAUD,S.LINARDOPOULOS,R.L.M.VAN MONTFORT,
JRNL AUTH 6 J.BLAGG
JRNL TITL STRUCTURE-BASED DESIGN OF ORALLY BIOAVAILABLE 1H-PYRROLO[3,
JRNL TITL 2 2-C]PYRIDINE INHIBITORS OF THE MITOTIC KINASE MONOPOLAR
JRNL TITL 3 SPINDLE 1 (MPS1).
JRNL REF J.MED.CHEM. V. 56 10045 2013
JRNL REFN ISSN 0022-2623
JRNL PMID 24256217
JRNL DOI 10.1021/JM401395S
REMARK 2
REMARK 2 RESOLUTION. 2.80 ANGSTROMS.
REMARK 3
REMARK 3 REFINEMENT.
REMARK 3 PROGRAM : BUSTER 2.11.4
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) : 2.80
REMARK 3 RESOLUTION RANGE LOW (ANGSTROMS) : 58.00
REMARK 3 DATA CUTOFF (SIGMA(F)) : 0.000
REMARK 3 COMPLETENESS FOR RANGE (%) : 88.0
REMARK 3 NUMBER OF REFLECTIONS : 9137
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) : 0.199
REMARK 3 R VALUE (WORKING SET) : 0.197
REMARK 3 FREE R VALUE : 0.241
REMARK 3 FREE R VALUE TEST SET SIZE (%) : 4.850
REMARK 3 FREE R VALUE TEST SET COUNT : 443
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 : 5
REMARK 3 BIN RESOLUTION RANGE HIGH (ANGSTROMS) : 2.80
REMARK 3 BIN RESOLUTION RANGE LOW (ANGSTROMS) : 3.13
REMARK 3 BIN COMPLETENESS (WORKING+TEST) (%) : 88.00
REMARK 3 REFLECTIONS IN BIN (WORKING + TEST SET) : 2415
REMARK 3 BIN R VALUE (WORKING + TEST SET) : 0.2177
REMARK 3 REFLECTIONS IN BIN (WORKING SET) : 2285
REMARK 3 BIN R VALUE (WORKING SET) : 0.2142
REMARK 3 BIN FREE R VALUE : 0.2754
REMARK 3 BIN FREE R VALUE TEST SET SIZE (%) : 5.38
REMARK 3 BIN FREE R VALUE TEST SET COUNT : 130
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 : 1950
REMARK 3 NUCLEIC ACID ATOMS : 0
REMARK 3 HETEROGEN ATOMS : 45
REMARK 3 SOLVENT ATOMS : 6
REMARK 3
REMARK 3 B VALUES.
REMARK 3 FROM WILSON PLOT (A**2) : 94.38
REMARK 3 MEAN B VALUE (OVERALL, A**2) : 77.38
REMARK 3 OVERALL ANISOTROPIC B VALUE.
REMARK 3 B11 (A**2) : 12.96000
REMARK 3 B22 (A**2) : -7.26110
REMARK 3 B33 (A**2) : -5.69890
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) : 0.379
REMARK 3 DPI (BLOW EQ-10) BASED ON R VALUE (A) : 0.742
REMARK 3 DPI (BLOW EQ-9) BASED ON FREE R VALUE (A) : 0.323
REMARK 3 DPI (CRUICKSHANK) BASED ON R VALUE (A) : 0.761
REMARK 3 DPI (CRUICKSHANK) BASED ON FREE R VALUE (A) : 0.329
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 : 0.938
REMARK 3 CORRELATION COEFFICIENT FO-FC FREE : 0.908
REMARK 3
REMARK 3 NUMBER OF GEOMETRIC FUNCTION TERMS DEFINED : 15
REMARK 3 TERM COUNT WEIGHT FUNCTION.
REMARK 3 BOND LENGTHS : 2041 ; 2.000 ; HARMONIC
REMARK 3 BOND ANGLES : 2779 ; 2.000 ; HARMONIC
REMARK 3 TORSION ANGLES : 679 ; 2.000 ; SINUSOIDAL
REMARK 3 TRIGONAL CARBON PLANES : 52 ; 2.000 ; HARMONIC
REMARK 3 GENERAL PLANES : 315 ; 5.000 ; HARMONIC
REMARK 3 ISOTROPIC THERMAL FACTORS : 2041 ; 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 : 274 ; 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 : 2335 ; 4.000 ; SEMIHARMONIC
REMARK 3
REMARK 3 RMS DEVIATIONS FROM IDEAL VALUES.
REMARK 3 BOND LENGTHS (A) : 0.010
REMARK 3 BOND ANGLES (DEGREES) : 1.14
REMARK 3 PEPTIDE OMEGA TORSION ANGLES (DEGREES) : 2.72
REMARK 3 OTHER TORSION ANGLES (DEGREES) : 20.96
REMARK 3
REMARK 3 TLS DETAILS
REMARK 3 NUMBER OF TLS GROUPS : 1
REMARK 3
REMARK 3 TLS GROUP : 1
REMARK 3 SELECTION: CHAIN A
REMARK 3 ORIGIN FOR THE GROUP (A): -4.4748 -36.8058 -22.3181
REMARK 3 T TENSOR
REMARK 3 T11: -0.4052 T22: -0.2697
REMARK 3 T33: -0.3621 T12: 0.0104
REMARK 3 T13: 0.0699 T23: 0.0624
REMARK 3 L TENSOR
REMARK 3 L11: 4.0091 L22: 1.5364
REMARK 3 L33: 2.1318 L12: 0.2873
REMARK 3 L13: 0.5567 L23: -0.1889
REMARK 3 S TENSOR
REMARK 3 S11: -0.0413 S12: -0.0818 S13: -0.4642
REMARK 3 S21: 0.0786 S22: -0.0186 S23: 0.1578
REMARK 3 S31: 0.0045 S32: 0.0008 S33: 0.0599
REMARK 3
REMARK 3 OTHER REFINEMENT REMARKS: NULL
REMARK 4
REMARK 4 4C4H COMPLIES WITH FORMAT V. 3.30, 13-JUL-11
REMARK 100
REMARK 100 THIS ENTRY HAS BEEN PROCESSED BY PDBE ON 05-SEP-13.
REMARK 100 THE DEPOSITION ID IS D_1290058238.
REMARK 200
REMARK 200 EXPERIMENTAL DETAILS
REMARK 200 EXPERIMENT TYPE : X-RAY DIFFRACTION
REMARK 200 DATE OF DATA COLLECTION : 23-MAY-11
REMARK 200 TEMPERATURE (KELVIN) : 100
REMARK 200 PH : 7.5
REMARK 200 NUMBER OF CRYSTALS USED : 1
REMARK 200
REMARK 200 SYNCHROTRON (Y/N) : Y
REMARK 200 RADIATION SOURCE : DIAMOND
REMARK 200 BEAMLINE : I04-1
REMARK 200 X-RAY GENERATOR MODEL : NULL
REMARK 200 MONOCHROMATIC OR LAUE (M/L) : M
REMARK 200 WAVELENGTH OR RANGE (A) : 0.9173
REMARK 200 MONOCHROMATOR : NULL
REMARK 200 OPTICS : NULL
REMARK 200
REMARK 200 DETECTOR TYPE : PIXEL
REMARK 200 DETECTOR MANUFACTURER : DECTRIS PILATUS
REMARK 200 INTENSITY-INTEGRATION SOFTWARE : MOSFLM
REMARK 200 DATA SCALING SOFTWARE : AIMLESS
REMARK 200
REMARK 200 NUMBER OF UNIQUE REFLECTIONS : 9139
REMARK 200 RESOLUTION RANGE HIGH (A) : 2.800
REMARK 200 RESOLUTION RANGE LOW (A) : 58.000
REMARK 200 REJECTION CRITERIA (SIGMA(I)) : 1.500
REMARK 200
REMARK 200 OVERALL.
REMARK 200 COMPLETENESS FOR RANGE (%) : 88.8
REMARK 200 DATA REDUNDANCY : 3.700
REMARK 200 R MERGE (I) : 0.05000
REMARK 200 R SYM (I) : NULL
REMARK 200 <I/SIGMA(I)> FOR THE DATA SET : 13.5000
REMARK 200
REMARK 200 IN THE HIGHEST RESOLUTION SHELL.
REMARK 200 HIGHEST RESOLUTION SHELL, RANGE HIGH (A) : 2.80
REMARK 200 HIGHEST RESOLUTION SHELL, RANGE LOW (A) : 2.95
REMARK 200 COMPLETENESS FOR SHELL (%) : 83.1
REMARK 200 DATA REDUNDANCY IN SHELL : 3.20
REMARK 200 R MERGE FOR SHELL (I) : 0.48000
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: PHASER
REMARK 200 STARTING MODEL: PDB ENTRY 4BI1
REMARK 200
REMARK 200 REMARK: NONE
REMARK 280
REMARK 280 CRYSTAL
REMARK 280 SOLVENT CONTENT, VS (%): 65.20
REMARK 280 MATTHEWS COEFFICIENT, VM (ANGSTROMS**3/DA): 3.50
REMARK 280
REMARK 280 CRYSTALLIZATION CONDITIONS: 30-35% AQUEOUS PEG300 ONLY, PH 7.5
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 34.83500
REMARK 290 SMTRY2 5 0.000000 1.000000 0.000000 52.34500
REMARK 290 SMTRY3 5 0.000000 0.000000 1.000000 55.89000
REMARK 290 SMTRY1 6 -1.000000 0.000000 0.000000 34.83500
REMARK 290 SMTRY2 6 0.000000 -1.000000 0.000000 52.34500
REMARK 290 SMTRY3 6 0.000000 0.000000 1.000000 55.89000
REMARK 290 SMTRY1 7 -1.000000 0.000000 0.000000 34.83500
REMARK 290 SMTRY2 7 0.000000 1.000000 0.000000 52.34500
REMARK 290 SMTRY3 7 0.000000 0.000000 -1.000000 55.89000
REMARK 290 SMTRY1 8 1.000000 0.000000 0.000000 34.83500
REMARK 290 SMTRY2 8 0.000000 -1.000000 0.000000 52.34500
REMARK 290 SMTRY3 8 0.000000 0.000000 -1.000000 55.89000
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 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 GLY A 534
REMARK 465 ASN A 669
REMARK 465 GLN A 670
REMARK 465 MET A 671
REMARK 465 GLN A 672
REMARK 465 PRO A 673
REMARK 465 ASP A 674
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 VAL A 684
REMARK 465 GLY A 685
REMARK 465 MET A 698
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 SER A 709
REMARK 465 LYS A 710
REMARK 465 THR A 795
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 CG CD CE NZ
REMARK 470 SER A 533 OG
REMARK 470 LYS A 538 CG CD CE NZ
REMARK 470 GLU A 545 CG CD OE1 OE2
REMARK 470 LYS A 546 CG CD CE NZ
REMARK 470 LYS A 547 CD CE NZ
REMARK 470 GLU A 559 CG CD OE1 OE2
REMARK 470 LYS A 577 CD CE NZ
REMARK 470 LYS A 614 CE NZ
REMARK 470 LYS A 615 CG CD CE NZ
REMARK 470 LYS A 616 CG CD CE NZ
REMARK 470 LYS A 617 CG CD CE NZ
REMARK 470 ILE A 619 CG1 CG2 CD1
REMARK 470 LYS A 696 CD CE NZ
REMARK 470 LYS A 731 CG CD CE NZ
REMARK 470 LYS A 743 CE NZ
REMARK 470 GLU A 755 CG CD OE1 OE2
REMARK 470 LYS A 762 CG CD CE NZ
REMARK 470 GLN A 765 CD OE1 NE2
REMARK 470 LYS A 769 CG CD CE NZ
REMARK 470 LYS A 777 CG CD CE NZ
REMARK 470 GLN A 794 CG CD OE1 NE2
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 -29.96 84.67
REMARK 500 LEU A 772 48.14 -93.72
REMARK 500
REMARK 500 REMARK: NULL
REMARK 610
REMARK 610 MISSING HETEROATOM
REMARK 610 THE FOLLOWING RESIDUES HAVE MISSING ATOMS (M=MODEL NUMBER;
REMARK 610 RES=RESIDUE NAME; C=CHAIN IDENTIFIER; SSEQ=SEQUENCE NUMBER;
REMARK 610 I=INSERTION CODE):
REMARK 610 M RES C SSEQI
REMARK 610 7PE A 1796
REMARK 800
REMARK 800 SITE
REMARK 800 SITE_IDENTIFIER: AC1
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: BINDING SITE FOR RESIDUE 7RO A 1795
REMARK 800
REMARK 800 SITE_IDENTIFIER: AC2
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: BINDING SITE FOR RESIDUE 7PE A 1796
REMARK 900
REMARK 900 RELATED ENTRIES
REMARK 900 RELATED ID: 4C4E RELATED DB: PDB
REMARK 900 STRUCTURE-BASED DESIGN OF ORALLY BIOAVAILABLE PYRROLOPYRIDINE
REMARK 900 INHIBITORS OF THE MITOTIC KINASE MPS1
REMARK 900 RELATED ID: 4C4F RELATED DB: PDB
REMARK 900 STRUCTURE-BASED DESIGN OF ORALLY BIOAVAILABLE PYRROLOPYRIDINE
REMARK 900 INHIBITORS OF THE MITOTIC KINASE MPS1
REMARK 900 RELATED ID: 4C4G RELATED DB: PDB
REMARK 900 STRUCTURE-BASED DESIGN OF ORALLY BIOAVAILABLE PYRROLOPYRIDINE
REMARK 900 INHIBITORS OF THE MITOTIC KINASE MPS1
REMARK 900 RELATED ID: 4C4I RELATED DB: PDB
REMARK 900 STRUCTURE-BASED DESIGN OF ORALLY BIOAVAILABLE PYRROLOPYRIDINE
REMARK 900 INHIBITORS OF THE MITOTIC KINASE MPS1
REMARK 900 RELATED ID: 4C4J RELATED DB: PDB
REMARK 900 STRUCTURE-BASED DESIGN OF ORALLY BIOAVAILABLE PYRROLOPYRIDINE
REMARK 900 INHIBITORS OF THE MITOTIC KINASE MPS1
REMARK 999
REMARK 999 SEQUENCE
REMARK 999 THE SEQUENCE INCLUDING HEXAHISTIDINE TAG IS AS DESCRIBED
REMARK 999 IN NAT. CHEM. BIOL. 2010, 6, 259-368.
DBREF 4C4H A 519 808 UNP P33981 TTK_HUMAN 519 808
SEQADV 4C4H MET A 496 UNP P33981 EXPRESSION TAG
SEQADV 4C4H HIS A 497 UNP P33981 EXPRESSION TAG
SEQADV 4C4H HIS A 498 UNP P33981 EXPRESSION TAG
SEQADV 4C4H HIS A 499 UNP P33981 EXPRESSION TAG
SEQADV 4C4H HIS A 500 UNP P33981 EXPRESSION TAG
SEQADV 4C4H HIS A 501 UNP P33981 EXPRESSION TAG
SEQADV 4C4H HIS A 502 UNP P33981 EXPRESSION TAG
SEQADV 4C4H SER A 503 UNP P33981 EXPRESSION TAG
SEQADV 4C4H SER A 504 UNP P33981 EXPRESSION TAG
SEQADV 4C4H GLY A 505 UNP P33981 EXPRESSION TAG
SEQADV 4C4H VAL A 506 UNP P33981 EXPRESSION TAG
SEQADV 4C4H ASP A 507 UNP P33981 EXPRESSION TAG
SEQADV 4C4H LEU A 508 UNP P33981 EXPRESSION TAG
SEQADV 4C4H GLY A 509 UNP P33981 EXPRESSION TAG
SEQADV 4C4H THR A 510 UNP P33981 EXPRESSION TAG
SEQADV 4C4H GLU A 511 UNP P33981 EXPRESSION TAG
SEQADV 4C4H ASN A 512 UNP P33981 EXPRESSION TAG
SEQADV 4C4H LEU A 513 UNP P33981 EXPRESSION TAG
SEQADV 4C4H TYR A 514 UNP P33981 EXPRESSION TAG
SEQADV 4C4H PHE A 515 UNP P33981 EXPRESSION TAG
SEQADV 4C4H GLN A 516 UNP P33981 EXPRESSION TAG
SEQADV 4C4H SER A 517 UNP P33981 EXPRESSION TAG
SEQADV 4C4H MET A 518 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 7RO A1795 35
HET 7PE A1796 10
HETNAM 7RO TERT-BUTYL 6-((2-CHLORO-4-(DIMETHYLCARBAMOYL)PHENYL)
HETNAM 2 7RO AMINO)-2-(1-METHYL-1H-PYRAZOL-4-YL)-1H-PYRROLO[3,2-
HETNAM 3 7RO C]PYRIDINE-1-CARBOXYLATE
HETNAM 7PE 2-(2-(2-(2-(2-(2-ETHOXYETHOXY)ETHOXY)ETHOXY)ETHOXY)
HETNAM 2 7PE ETHOXY)ETHANOL
HETSYN 7PE POLYETHYLENE GLYCOL FRAGMENT
FORMUL 2 7RO C25 H27 CL N6 O3
FORMUL 3 7PE C14 H30 O7
FORMUL 4 HOH *6(H2 O)
HELIX 1 1 ASP A 561 GLN A 580 1 20
HELIX 2 2 LEU A 609 LYS A 616 1 8
HELIX 3 3 ASP A 620 GLN A 640 1 21
HELIX 4 4 LYS A 649 ALA A 651 5 3
HELIX 5 5 PRO A 691 LYS A 696 1 6
HELIX 6 6 SER A 712 GLY A 730 1 19
HELIX 7 7 ASN A 739 ASP A 749 1 11
HELIX 8 8 GLU A 761 LEU A 772 1 12
HELIX 9 9 SER A 781 LEU A 786 1 6
HELIX 10 10 HIS A 788 ILE A 793 1 6
SHEET 1 AA 6 SER A 517 VAL A 520 0
SHEET 2 AA 6 ARG A 523 GLY A 532 -1 O ARG A 523 N VAL A 520
SHEET 3 AA 6 SER A 537 LEU A 543 -1 O VAL A 539 N ILE A 531
SHEET 4 AA 6 ILE A 549 ASN A 556 -1 O TYR A 550 N VAL A 542
SHEET 5 AA 6 TYR A 597 GLU A 603 -1 O ILE A 598 N VAL A 555
SHEET 6 AA 6 LEU A 588 ILE A 593 -1 N TYR A 589 O VAL A 601
SHEET 1 AB 3 ILE A 607 ASP A 608 0
SHEET 2 AB 3 PHE A 653 ILE A 655 -1 N ILE A 655 O ILE A 607
SHEET 3 AB 3 LEU A 660 LEU A 662 -1 O LYS A 661 N LEU A 654
SITE 1 AC1 15 ILE A 531 VAL A 539 GLN A 541 ALA A 551
SITE 2 AC1 15 LYS A 553 MET A 602 GLU A 603 CYS A 604
SITE 3 AC1 15 GLY A 605 ILE A 607 ASP A 608 SER A 611
SITE 4 AC1 15 LEU A 654 ILE A 663 7PE A1796
SITE 1 AC2 6 SER A 537 LYS A 553 TYR A 568 GLU A 571
SITE 2 AC2 6 ASP A 664 7RO A1795
CRYST1 69.670 104.690 111.780 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 0.014353 0.000000 0.000000 0.00000
SCALE2 0.000000 0.009552 0.000000 0.00000
SCALE3 0.000000 0.000000 0.008946 0.00000
(ATOM LINES ARE NOT SHOWN.)
END
