HEADER TRANSFERASE 29-SEP-14 3WZJ
TITLE CRYSTAL STRUCTURE OF HUMAN MPS1 CATALYTIC DOMAIN IN COMPLEX WITH 4-(6-
TITLE 2 (CYCLOHEXYLAMINO)-8-(((TETRAHYDRO-2H-PYRAN-4-YL)METHYL)AMINO)
TITLE 3 IMIDAZO[1,2-B]PYRIDAZIN-3-YL)-N-CYCLOPROPYLBENZAMIDE
COMPND MOL_ID: 1;
COMPND 2 MOLECULE: DUAL SPECIFICITY PROTEIN KINASE TTK;
COMPND 3 CHAIN: A;
COMPND 4 FRAGMENT: MPS1 KINASE DOMAIN, UNP RESIDUES 516-820;
COMPND 5 SYNONYM: PHOSPHOTYROSINE PICKED THREONINE-PROTEIN KINASE, PYT;
COMPND 6 EC: 2.7.12.1;
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 GENE: TTK, MPS1, MPS1L1;
SOURCE 6 EXPRESSION_SYSTEM: CELL-FREE SYNTHESIS
KEYWDS TRANSFERASE, ATP BINDING, PHOSPHORYLATION
EXPDTA X-RAY DIFFRACTION
AUTHOR K.KUSAKABE,N.IDE,Y.DAIGO,T.ITOH,T.YAMAMOTO,E.KOJIMA,Y.MITSUOKA,
AUTHOR 2 G.TADANO,S.TAGASHIRA,K.HIGASHINO,Y.OKANO,Y.SATO,M.INOUE,M.IGUCHI,
AUTHOR 3 T.KANAZAWA,Y.ISHIOKA,K.DOHI,Y.KIDO,S.SAKAMOTO,S.ANDO,M.MAEDA,
AUTHOR 4 M.HIGAKI,H.YOSHIZAWA,H.MURA,Y.NAKAMURA
REVDAT 3 24-AUG-22 3WZJ 1 JRNL REMARK SEQADV
REVDAT 2 22-NOV-17 3WZJ 1 REMARK
REVDAT 1 11-FEB-15 3WZJ 0
JRNL AUTH K.KUSAKABE,N.IDE,Y.DAIGO,T.ITOH,T.YAMAMOTO,H.HASHIZUME,
JRNL AUTH 2 K.NOZU,H.YOSHIDA,G.TADANO,S.TAGASHIRA,K.HIGASHINO,Y.OKANO,
JRNL AUTH 3 Y.SATO,M.INOUE,M.IGUCHI,T.KANAZAWA,Y.ISHIOKA,K.DOHI,Y.KIDO,
JRNL AUTH 4 S.SAKAMOTO,S.ANDO,M.MAEDA,M.HIGAKI,Y.BABA,Y.NAKAMURA
JRNL TITL DISCOVERY OF IMIDAZO[1,2-B]PYRIDAZINE DERIVATIVES: SELECTIVE
JRNL TITL 2 AND ORALLY AVAILABLE MPS1 (TTK) KINASE INHIBITORS EXHIBITING
JRNL TITL 3 REMARKABLE ANTIPROLIFERATIVE ACTIVITY.
JRNL REF J.MED.CHEM. V. 58 1760 2015
JRNL REFN ISSN 0022-2623
JRNL PMID 25625617
JRNL DOI 10.1021/JM501599U
REMARK 2
REMARK 2 RESOLUTION. 2.75 ANGSTROMS.
REMARK 3
REMARK 3 REFINEMENT.
REMARK 3 PROGRAM : REFMAC 5.7.0029
REMARK 3 AUTHORS : MURSHUDOV,SKUBAK,LEBEDEV,PANNU,STEINER,
REMARK 3 : NICHOLLS,WINN,LONG,VAGIN
REMARK 3
REMARK 3 REFINEMENT TARGET : MAXIMUM LIKELIHOOD
REMARK 3
REMARK 3 DATA USED IN REFINEMENT.
REMARK 3 RESOLUTION RANGE HIGH (ANGSTROMS) : 2.75
REMARK 3 RESOLUTION RANGE LOW (ANGSTROMS) : 20.00
REMARK 3 DATA CUTOFF (SIGMA(F)) : 0.000
REMARK 3 COMPLETENESS FOR RANGE (%) : 87.0
REMARK 3 NUMBER OF REFLECTIONS : 9466
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) : 0.227
REMARK 3 R VALUE (WORKING SET) : 0.221
REMARK 3 FREE R VALUE : 0.282
REMARK 3 FREE R VALUE TEST SET SIZE (%) : 9.700
REMARK 3 FREE R VALUE TEST SET COUNT : 1016
REMARK 3
REMARK 3 FIT IN THE HIGHEST RESOLUTION BIN.
REMARK 3 TOTAL NUMBER OF BINS USED : 20
REMARK 3 BIN RESOLUTION RANGE HIGH (A) : 2.75
REMARK 3 BIN RESOLUTION RANGE LOW (A) : 2.82
REMARK 3 REFLECTION IN BIN (WORKING SET) : 681
REMARK 3 BIN COMPLETENESS (WORKING+TEST) (%) : 87.38
REMARK 3 BIN R VALUE (WORKING SET) : 0.3220
REMARK 3 BIN FREE R VALUE SET COUNT : 74
REMARK 3 BIN FREE R VALUE : 0.3920
REMARK 3
REMARK 3 NUMBER OF NON-HYDROGEN ATOMS USED IN REFINEMENT.
REMARK 3 PROTEIN ATOMS : 2015
REMARK 3 NUCLEIC ACID ATOMS : 0
REMARK 3 HETEROGEN ATOMS : 36
REMARK 3 SOLVENT ATOMS : 2
REMARK 3
REMARK 3 B VALUES.
REMARK 3 FROM WILSON PLOT (A**2) : NULL
REMARK 3 MEAN B VALUE (OVERALL, A**2) : 63.81
REMARK 3 OVERALL ANISOTROPIC B VALUE.
REMARK 3 B11 (A**2) : -2.77000
REMARK 3 B22 (A**2) : 5.16000
REMARK 3 B33 (A**2) : -2.39000
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 OVERALL COORDINATE ERROR.
REMARK 3 ESU BASED ON R VALUE (A): 0.841
REMARK 3 ESU BASED ON FREE R VALUE (A): 0.391
REMARK 3 ESU BASED ON MAXIMUM LIKELIHOOD (A): 0.285
REMARK 3 ESU FOR B VALUES BASED ON MAXIMUM LIKELIHOOD (A**2): 14.237
REMARK 3
REMARK 3 CORRELATION COEFFICIENTS.
REMARK 3 CORRELATION COEFFICIENT FO-FC : 0.935
REMARK 3 CORRELATION COEFFICIENT FO-FC FREE : 0.910
REMARK 3
REMARK 3 RMS DEVIATIONS FROM IDEAL VALUES COUNT RMS WEIGHT
REMARK 3 BOND LENGTHS REFINED ATOMS (A): 2099 ; 0.007 ; 0.019
REMARK 3 BOND LENGTHS OTHERS (A): NULL ; NULL ; NULL
REMARK 3 BOND ANGLES REFINED ATOMS (DEGREES): 2853 ; 1.200 ; 1.982
REMARK 3 BOND ANGLES OTHERS (DEGREES): NULL ; NULL ; NULL
REMARK 3 TORSION ANGLES, PERIOD 1 (DEGREES): 254 ; 5.556 ; 5.000
REMARK 3 TORSION ANGLES, PERIOD 2 (DEGREES): 93 ;42.149 ;25.699
REMARK 3 TORSION ANGLES, PERIOD 3 (DEGREES): 349 ;18.353 ;15.000
REMARK 3 TORSION ANGLES, PERIOD 4 (DEGREES): 5 ;19.646 ;15.000
REMARK 3 CHIRAL-CENTER RESTRAINTS (A**3): 317 ; 0.075 ; 0.200
REMARK 3 GENERAL PLANES REFINED ATOMS (A): 1577 ; 0.005 ; 0.021
REMARK 3 GENERAL PLANES OTHERS (A): NULL ; NULL ; NULL
REMARK 3 NON-BONDED CONTACTS REFINED ATOMS (A): NULL ; NULL ; NULL
REMARK 3 NON-BONDED CONTACTS OTHERS (A): NULL ; NULL ; NULL
REMARK 3 NON-BONDED TORSION REFINED ATOMS (A): NULL ; NULL ; NULL
REMARK 3 NON-BONDED TORSION OTHERS (A): NULL ; NULL ; NULL
REMARK 3 H-BOND (X...Y) REFINED ATOMS (A): NULL ; NULL ; NULL
REMARK 3 H-BOND (X...Y) OTHERS (A): NULL ; NULL ; NULL
REMARK 3 POTENTIAL METAL-ION REFINED ATOMS (A): NULL ; NULL ; NULL
REMARK 3 POTENTIAL METAL-ION OTHERS (A): NULL ; NULL ; NULL
REMARK 3 SYMMETRY VDW REFINED ATOMS (A): NULL ; NULL ; NULL
REMARK 3 SYMMETRY VDW OTHERS (A): NULL ; NULL ; NULL
REMARK 3 SYMMETRY H-BOND REFINED ATOMS (A): NULL ; NULL ; NULL
REMARK 3 SYMMETRY H-BOND OTHERS (A): NULL ; NULL ; NULL
REMARK 3 SYMMETRY METAL-ION REFINED ATOMS (A): NULL ; NULL ; NULL
REMARK 3 SYMMETRY METAL-ION OTHERS (A): NULL ; NULL ; NULL
REMARK 3
REMARK 3 ISOTROPIC THERMAL FACTOR RESTRAINTS. COUNT RMS WEIGHT
REMARK 3 MAIN-CHAIN BOND REFINED ATOMS (A**2): NULL ; NULL ; NULL
REMARK 3 MAIN-CHAIN BOND OTHER ATOMS (A**2): NULL ; NULL ; NULL
REMARK 3 MAIN-CHAIN ANGLE REFINED ATOMS (A**2): NULL ; NULL ; NULL
REMARK 3 MAIN-CHAIN ANGLE OTHER ATOMS (A**2): NULL ; NULL ; NULL
REMARK 3 SIDE-CHAIN BOND REFINED ATOMS (A**2): NULL ; NULL ; NULL
REMARK 3 SIDE-CHAIN BOND OTHER ATOMS (A**2): NULL ; NULL ; NULL
REMARK 3 SIDE-CHAIN ANGLE REFINED ATOMS (A**2): NULL ; NULL ; NULL
REMARK 3 SIDE-CHAIN ANGLE OTHER ATOMS (A**2): NULL ; NULL ; NULL
REMARK 3 LONG RANGE B REFINED ATOMS (A**2): NULL ; NULL ; NULL
REMARK 3 LONG RANGE B OTHER ATOMS (A**2): NULL ; NULL ; NULL
REMARK 3
REMARK 3 ANISOTROPIC THERMAL FACTOR RESTRAINTS. COUNT RMS WEIGHT
REMARK 3 RIGID-BOND RESTRAINTS (A**2): NULL ; NULL ; NULL
REMARK 3 SPHERICITY; FREE ATOMS (A**2): NULL ; NULL ; NULL
REMARK 3 SPHERICITY; BONDED ATOMS (A**2): NULL ; NULL ; NULL
REMARK 3
REMARK 3 NCS RESTRAINTS STATISTICS
REMARK 3 NUMBER OF DIFFERENT NCS GROUPS : NULL
REMARK 3
REMARK 3 TLS DETAILS
REMARK 3 NUMBER OF TLS GROUPS : NULL
REMARK 3
REMARK 3 BULK SOLVENT MODELLING.
REMARK 3 METHOD USED : BABINET MODEL WITH MASK
REMARK 3 PARAMETERS FOR MASK CALCULATION
REMARK 3 VDW PROBE RADIUS : 1.20
REMARK 3 ION PROBE RADIUS : 0.80
REMARK 3 SHRINKAGE RADIUS : 0.80
REMARK 3
REMARK 3 OTHER REFINEMENT REMARKS: HYDROGENS HAVE BEEN USED IF PRESENT IN
REMARK 3 THE INPUT U VALUES : REFINED INDIVIDUALLY
REMARK 4
REMARK 4 3WZJ COMPLIES WITH FORMAT V. 3.30, 13-JUL-11
REMARK 100
REMARK 100 THIS ENTRY HAS BEEN PROCESSED BY PDBJ ON 02-OCT-14.
REMARK 100 THE DEPOSITION ID IS D_1000096989.
REMARK 200
REMARK 200 EXPERIMENTAL DETAILS
REMARK 200 EXPERIMENT TYPE : X-RAY DIFFRACTION
REMARK 200 DATE OF DATA COLLECTION : 31-JUL-09
REMARK 200 TEMPERATURE (KELVIN) : 100
REMARK 200 PH : 7.5
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 : IMAGE PLATE
REMARK 200 DETECTOR MANUFACTURER : RIGAKU RAXIS IV++
REMARK 200 INTENSITY-INTEGRATION SOFTWARE : DENZO, HKL-2000
REMARK 200 DATA SCALING SOFTWARE : SCALEPACK, HKL-2000
REMARK 200
REMARK 200 NUMBER OF UNIQUE REFLECTIONS : 10489
REMARK 200 RESOLUTION RANGE HIGH (A) : 2.750
REMARK 200 RESOLUTION RANGE LOW (A) : 50.000
REMARK 200 REJECTION CRITERIA (SIGMA(I)) : NULL
REMARK 200
REMARK 200 OVERALL.
REMARK 200 COMPLETENESS FOR RANGE (%) : 87.2
REMARK 200 DATA REDUNDANCY : 3.500
REMARK 200 R MERGE (I) : 0.06200
REMARK 200 R SYM (I) : NULL
REMARK 200 <I/SIGMA(I)> FOR THE DATA SET : 12.6000
REMARK 200
REMARK 200 IN THE HIGHEST RESOLUTION SHELL.
REMARK 200 HIGHEST RESOLUTION SHELL, RANGE HIGH (A) : 2.75
REMARK 200 HIGHEST RESOLUTION SHELL, RANGE LOW (A) : 2.80
REMARK 200 COMPLETENESS FOR SHELL (%) : 88.9
REMARK 200 DATA REDUNDANCY IN SHELL : 3.20
REMARK 200 R MERGE FOR SHELL (I) : 0.44000
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: MOLECULAR REPLACEMENT
REMARK 200 SOFTWARE USED: MOLREP
REMARK 200 STARTING MODEL: NULL
REMARK 200
REMARK 200 REMARK: NULL
REMARK 280
REMARK 280 CRYSTAL
REMARK 280 SOLVENT CONTENT, VS (%): 59.51
REMARK 280 MATTHEWS COEFFICIENT, VM (ANGSTROMS**3/DA): 3.04
REMARK 280
REMARK 280 CRYSTALLIZATION CONDITIONS: 0.1M TRIS HYDROCHLORIDE PH7.5, 0.12M
REMARK 280 MAGNESIUM CHLORIDE, 8%(W/V) TRIETHYLENE GLYCOL , VAPOR DIFFUSION,
REMARK 280 SITTING DROP, TEMPERATURE 293K
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 35.48050
REMARK 290 SMTRY2 5 0.000000 1.000000 0.000000 55.19450
REMARK 290 SMTRY3 5 0.000000 0.000000 1.000000 57.17800
REMARK 290 SMTRY1 6 -1.000000 0.000000 0.000000 35.48050
REMARK 290 SMTRY2 6 0.000000 -1.000000 0.000000 55.19450
REMARK 290 SMTRY3 6 0.000000 0.000000 1.000000 57.17800
REMARK 290 SMTRY1 7 -1.000000 0.000000 0.000000 35.48050
REMARK 290 SMTRY2 7 0.000000 1.000000 0.000000 55.19450
REMARK 290 SMTRY3 7 0.000000 0.000000 -1.000000 57.17800
REMARK 290 SMTRY1 8 1.000000 0.000000 0.000000 35.48050
REMARK 290 SMTRY2 8 0.000000 -1.000000 0.000000 55.19450
REMARK 290 SMTRY3 8 0.000000 0.000000 -1.000000 57.17800
REMARK 290
REMARK 290 REMARK: NULL
REMARK 300
REMARK 300 BIOMOLECULE: 1, 2
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 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 350
REMARK 350 BIOMOLECULE: 2
REMARK 350 SOFTWARE DETERMINED QUATERNARY STRUCTURE: DIMERIC
REMARK 350 SOFTWARE USED: PISA
REMARK 350 TOTAL BURIED SURFACE AREA: 1280 ANGSTROM**2
REMARK 350 SURFACE AREA OF THE COMPLEX: 23700 ANGSTROM**2
REMARK 350 CHANGE IN SOLVENT FREE ENERGY: -13.0 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 350 BIOMT1 2 -1.000000 0.000000 0.000000 -70.96100
REMARK 350 BIOMT2 2 0.000000 -1.000000 0.000000 0.00000
REMARK 350 BIOMT3 2 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 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 VAL A 684
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 465 MET A 809
REMARK 465 LYS A 810
REMARK 465 TYR A 811
REMARK 465 VAL A 812
REMARK 465 LEU A 813
REMARK 465 GLY A 814
REMARK 465 GLN A 815
REMARK 465 LEU A 816
REMARK 465 VAL A 817
REMARK 465 GLY A 818
REMARK 465 LEU A 819
REMARK 465 ASN A 820
REMARK 465 LEU A 821
REMARK 465 VAL A 822
REMARK 465 PRO A 823
REMARK 465 ARG A 824
REMARK 465 GLY A 825
REMARK 465 SER A 826
REMARK 465 ALA A 827
REMARK 465 ALA A 828
REMARK 465 GLY A 829
REMARK 465 HIS A 830
REMARK 465 HIS A 831
REMARK 465 HIS A 832
REMARK 465 HIS A 833
REMARK 465 HIS A 834
REMARK 465 HIS A 835
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 SER A 519 OG
REMARK 470 LYS A 521 CE NZ
REMARK 470 ARG A 523 CZ NH1 NH2
REMARK 470 LYS A 529 CD CE NZ
REMARK 470 SER A 533 OG
REMARK 470 SER A 536 OG
REMARK 470 LYS A 546 CE NZ
REMARK 470 LYS A 547 CG CD CE NZ
REMARK 470 GLU A 558 CG CD OE1 OE2
REMARK 470 GLU A 559 CG CD OE1 OE2
REMARK 470 LYS A 577 CE NZ
REMARK 470 LYS A 614 CE NZ
REMARK 470 LYS A 615 CG CD CE NZ
REMARK 470 LYS A 616 NZ
REMARK 470 LYS A 617 CG CD CE NZ
REMARK 470 ILE A 619 CG1 CG2 CD1
REMARK 470 TRP A 622 CG CD1 CD2 NE1 CE2 CE3 CZ2
REMARK 470 TRP A 622 CZ3 CH2
REMARK 470 SER A 646 OG
REMARK 470 ASP A 657 CG OD1 OD2
REMARK 470 ASN A 669 CG OD1 ND2
REMARK 470 LYS A 696 CG CD CE NZ
REMARK 470 ILE A 711 CD1
REMARK 470 ILE A 741 CG1 CG2 CD1
REMARK 470 SER A 742 OG
REMARK 470 HIS A 745 CG ND1 CD2 CE1 NE2
REMARK 470 ILE A 759 CG1 CG2 CD1
REMARK 470 LYS A 762 CE NZ
REMARK 470 LYS A 769 CE NZ
REMARK 470 LYS A 773 CD CE NZ
REMARK 470 LYS A 777 CG 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 LYS A 521 57.68 31.09
REMARK 500 LEU A 528 -78.88 -62.73
REMARK 500 GLU A 559 65.22 -103.73
REMARK 500 ILE A 586 128.25 -37.95
REMARK 500 THR A 594 -164.10 -127.04
REMARK 500 SER A 646 -18.04 80.42
REMARK 500 ASP A 647 37.01 -142.41
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 O43 A 901
REMARK 900
REMARK 900 RELATED ENTRIES
REMARK 900 RELATED ID: 3WZK RELATED DB: PDB
DBREF 3WZJ A 516 820 UNP P33981 TTK_HUMAN 516 820
SEQADV 3WZJ MET A 515 UNP P33981 EXPRESSION TAG
SEQADV 3WZJ LEU A 821 UNP P33981 EXPRESSION TAG
SEQADV 3WZJ VAL A 822 UNP P33981 EXPRESSION TAG
SEQADV 3WZJ PRO A 823 UNP P33981 EXPRESSION TAG
SEQADV 3WZJ ARG A 824 UNP P33981 EXPRESSION TAG
SEQADV 3WZJ GLY A 825 UNP P33981 EXPRESSION TAG
SEQADV 3WZJ SER A 826 UNP P33981 EXPRESSION TAG
SEQADV 3WZJ ALA A 827 UNP P33981 EXPRESSION TAG
SEQADV 3WZJ ALA A 828 UNP P33981 EXPRESSION TAG
SEQADV 3WZJ GLY A 829 UNP P33981 EXPRESSION TAG
SEQADV 3WZJ HIS A 830 UNP P33981 EXPRESSION TAG
SEQADV 3WZJ HIS A 831 UNP P33981 EXPRESSION TAG
SEQADV 3WZJ HIS A 832 UNP P33981 EXPRESSION TAG
SEQADV 3WZJ HIS A 833 UNP P33981 EXPRESSION TAG
SEQADV 3WZJ HIS A 834 UNP P33981 EXPRESSION TAG
SEQADV 3WZJ HIS A 835 UNP P33981 EXPRESSION TAG
SEQRES 1 A 321 MET GLU CYS ILE SER VAL LYS GLY ARG ILE TYR SER ILE
SEQRES 2 A 321 LEU LYS GLN ILE GLY SER GLY GLY SER SER LYS VAL PHE
SEQRES 3 A 321 GLN VAL LEU ASN GLU LYS LYS GLN ILE TYR ALA ILE LYS
SEQRES 4 A 321 TYR VAL ASN LEU GLU GLU ALA ASP ASN GLN THR LEU ASP
SEQRES 5 A 321 SER TYR ARG ASN GLU ILE ALA TYR LEU ASN LYS LEU GLN
SEQRES 6 A 321 GLN HIS SER ASP LYS ILE ILE ARG LEU TYR ASP TYR GLU
SEQRES 7 A 321 ILE THR ASP GLN TYR ILE TYR MET VAL MET GLU CYS GLY
SEQRES 8 A 321 ASN ILE ASP LEU ASN SER TRP LEU LYS LYS LYS LYS SER
SEQRES 9 A 321 ILE ASP PRO TRP GLU ARG LYS SER TYR TRP LYS ASN MET
SEQRES 10 A 321 LEU GLU ALA VAL HIS THR ILE HIS GLN HIS GLY ILE VAL
SEQRES 11 A 321 HIS SER ASP LEU LYS PRO ALA ASN PHE LEU ILE VAL ASP
SEQRES 12 A 321 GLY MET LEU LYS LEU ILE ASP PHE GLY ILE ALA ASN GLN
SEQRES 13 A 321 MET GLN PRO ASP THR THR SER VAL VAL LYS ASP SER GLN
SEQRES 14 A 321 VAL GLY THR VAL ASN TYR MET PRO PRO GLU ALA ILE LYS
SEQRES 15 A 321 ASP MET SER SER SER ARG GLU ASN GLY LYS SER LYS SER
SEQRES 16 A 321 LYS ILE SER PRO LYS SER ASP VAL TRP SER LEU GLY CYS
SEQRES 17 A 321 ILE LEU TYR TYR MET THR TYR GLY LYS THR PRO PHE GLN
SEQRES 18 A 321 GLN ILE ILE ASN GLN ILE SER LYS LEU HIS ALA ILE ILE
SEQRES 19 A 321 ASP PRO ASN HIS GLU ILE GLU PHE PRO ASP ILE PRO GLU
SEQRES 20 A 321 LYS ASP LEU GLN ASP VAL LEU LYS CYS CYS LEU LYS ARG
SEQRES 21 A 321 ASP PRO LYS GLN ARG ILE SER ILE PRO GLU LEU LEU ALA
SEQRES 22 A 321 HIS PRO TYR VAL GLN ILE GLN THR HIS PRO VAL ASN GLN
SEQRES 23 A 321 MET ALA LYS GLY THR THR GLU GLU MET LYS TYR VAL LEU
SEQRES 24 A 321 GLY GLN LEU VAL GLY LEU ASN LEU VAL PRO ARG GLY SER
SEQRES 25 A 321 ALA ALA GLY HIS HIS HIS HIS HIS HIS
HET O43 A 901 36
HETNAM O43 4-{6-(CYCLOHEXYLAMINO)-8-[(TETRAHYDRO-2H-PYRAN-4-
HETNAM 2 O43 YLMETHYL)AMINO]IMIDAZO[1,2-B]PYRIDAZIN-3-YL}-N-
HETNAM 3 O43 CYCLOPROPYLBENZAMIDE
FORMUL 2 O43 C28 H36 N6 O2
FORMUL 3 HOH *2(H2 O)
HELIX 1 1 ASP A 561 GLN A 579 1 19
HELIX 2 2 LEU A 609 LYS A 616 1 8
HELIX 3 3 ASP A 620 HIS A 641 1 22
HELIX 4 4 LYS A 649 ALA A 651 5 3
HELIX 5 5 PRO A 691 ASP A 697 1 7
HELIX 6 6 PRO A 713 TYR A 729 1 17
HELIX 7 7 ASN A 739 ILE A 748 1 10
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 A 6 ILE A 518 VAL A 520 0
SHEET 2 A 6 ARG A 523 SER A 533 -1 O TYR A 525 N ILE A 518
SHEET 3 A 6 SER A 537 ASN A 544 -1 O LEU A 543 N SER A 526
SHEET 4 A 6 ILE A 549 ASN A 556 -1 O TYR A 554 N LYS A 538
SHEET 5 A 6 TYR A 597 MET A 602 -1 O MET A 602 N ALA A 551
SHEET 6 A 6 LEU A 588 ILE A 593 -1 N TYR A 589 O VAL A 601
SHEET 1 B 3 ILE A 518 VAL A 520 0
SHEET 2 B 3 ARG A 523 SER A 533 -1 O TYR A 525 N ILE A 518
SHEET 3 B 3 GLN A 672 PRO A 673 -1 O GLN A 672 N SER A 533
SHEET 1 C 3 ILE A 607 ASP A 608 0
SHEET 2 C 3 PHE A 653 VAL A 656 -1 O ILE A 655 N ILE A 607
SHEET 3 C 3 MET A 659 LEU A 662 -1 O MET A 659 N VAL A 656
CISPEP 1 GLU A 516 CYS A 517 0 4.66
CISPEP 2 GLY A 534 GLY A 535 0 3.94
SITE 1 AC1 14 ILE A 531 GLN A 541 ALA A 551 LYS A 553
SITE 2 AC1 14 GLU A 571 MET A 600 MET A 602 GLU A 603
SITE 3 AC1 14 CYS A 604 GLY A 605 ASN A 606 LEU A 654
SITE 4 AC1 14 ILE A 663 MET A 671
CRYST1 70.961 110.389 114.356 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 0.014092 0.000000 0.000000 0.00000
SCALE2 0.000000 0.009059 0.000000 0.00000
SCALE3 0.000000 0.000000 0.008745 0.00000
(ATOM LINES ARE NOT SHOWN.)
END
