HEADER TRANSFERASE 24-FEB-16 5IDN
TITLE CDK8-CYCC IN COMPLEX WITH [(S)-2-(4-CHLORO-PHENYL)-PYRROLIDIN-1-YL]-
TITLE 2 (3-METHYL-1H-PYRAZOLO[3,4-B]PYRIDIN-5-YL)-METHANONE
COMPND MOL_ID: 1;
COMPND 2 MOLECULE: CYCLIN-DEPENDENT KINASE 8;
COMPND 3 CHAIN: A;
COMPND 4 FRAGMENT: KINASE DOMAIN, RESIDUES 3-405;
COMPND 5 SYNONYM: CELL DIVISION PROTEIN KINASE 8,MEDIATOR COMPLEX SUBUNIT
COMPND 6 CDK8,MEDIATOR OF RNA POLYMERASE II TRANSCRIPTION SUBUNIT CDK8,PROTEIN
COMPND 7 KINASE K35;
COMPND 8 EC: 2.7.11.22,2.7.11.23;
COMPND 9 ENGINEERED: YES;
COMPND 10 MOL_ID: 2;
COMPND 11 MOLECULE: CYCLIN-C;
COMPND 12 CHAIN: B;
COMPND 13 SYNONYM: SRB11 HOMOLOG,HSRB11;
COMPND 14 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: CDK8;
SOURCE 6 EXPRESSION_SYSTEM: SPODOPTERA FRUGIPERDA;
SOURCE 7 EXPRESSION_SYSTEM_COMMON: FALL ARMYWORM;
SOURCE 8 EXPRESSION_SYSTEM_TAXID: 7108;
SOURCE 9 MOL_ID: 2;
SOURCE 10 ORGANISM_SCIENTIFIC: HOMO SAPIENS;
SOURCE 11 ORGANISM_COMMON: HUMAN;
SOURCE 12 ORGANISM_TAXID: 9606;
SOURCE 13 GENE: CCNC;
SOURCE 14 EXPRESSION_SYSTEM: SPODOPTERA FRUGIPERDA;
SOURCE 15 EXPRESSION_SYSTEM_COMMON: FALL ARMYWORM;
SOURCE 16 EXPRESSION_SYSTEM_TAXID: 7108
KEYWDS CDK8 KINASE / CYCLIN C, TRANSFERASE
EXPDTA X-RAY DIFFRACTION
AUTHOR D.MUSIL,J.BLAGG,A.MALLINGER,P.CZODROWSKI,K.SCHIEMANN
REVDAT 2 10-JAN-24 5IDN 1 REMARK
REVDAT 1 21-DEC-16 5IDN 0
JRNL AUTH P.CZODROWSKI,A.MALLINGER,D.WIENKE,C.ESDAR,O.POSCHKE,M.BUSCH,
JRNL AUTH 2 F.ROHDICH,S.A.ECCLES,M.J.ORTIZ-RUIZ,R.SCHNEIDER,F.I.RAYNAUD,
JRNL AUTH 3 P.A.CLARKE,D.MUSIL,D.SCHWARZ,T.DALE,K.URBAHNS,J.BLAGG,
JRNL AUTH 4 K.SCHIEMANN
JRNL TITL STRUCTURE-BASED OPTIMIZATION OF POTENT, SELECTIVE, AND
JRNL TITL 2 ORALLY BIOAVAILABLE CDK8 INHIBITORS DISCOVERED BY
JRNL TITL 3 HIGH-THROUGHPUT SCREENING.
JRNL REF J. MED. CHEM. V. 59 9337 2016
JRNL REFN ISSN 1520-4804
JRNL PMID 27490956
JRNL DOI 10.1021/ACS.JMEDCHEM.6B00597
REMARK 2
REMARK 2 RESOLUTION. 2.26 ANGSTROMS.
REMARK 3
REMARK 3 REFINEMENT.
REMARK 3 PROGRAM : REFMAC 5.2.0005
REMARK 3 AUTHORS : MURSHUDOV,SKUBAK,LEBEDEV,PANNU,STEINER,
REMARK 3 : NICHOLLS,WINN,LONG,VAGIN
REMARK 3
REMARK 3 REFINEMENT TARGET : NULL
REMARK 3
REMARK 3 DATA USED IN REFINEMENT.
REMARK 3 RESOLUTION RANGE HIGH (ANGSTROMS) : 2.26
REMARK 3 RESOLUTION RANGE LOW (ANGSTROMS) : 84.01
REMARK 3 DATA CUTOFF (SIGMA(F)) : NULL
REMARK 3 COMPLETENESS FOR RANGE (%) : 98.2
REMARK 3 NUMBER OF REFLECTIONS : 39547
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) : 0.221
REMARK 3 R VALUE (WORKING SET) : 0.220
REMARK 3 FREE R VALUE : 0.253
REMARK 3 FREE R VALUE TEST SET SIZE (%) : 3.300
REMARK 3 FREE R VALUE TEST SET COUNT : 1353
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) : 2.26
REMARK 3 BIN RESOLUTION RANGE LOW (A) : 2.32
REMARK 3 REFLECTION IN BIN (WORKING SET) : 2859
REMARK 3 BIN COMPLETENESS (WORKING+TEST) (%) : 98.38
REMARK 3 BIN R VALUE (WORKING SET) : 0.3620
REMARK 3 BIN FREE R VALUE SET COUNT : 118
REMARK 3 BIN FREE R VALUE : 0.3570
REMARK 3
REMARK 3 NUMBER OF NON-HYDROGEN ATOMS USED IN REFINEMENT.
REMARK 3 PROTEIN ATOMS : 5000
REMARK 3 NUCLEIC ACID ATOMS : 0
REMARK 3 HETEROGEN ATOMS : 46
REMARK 3 SOLVENT ATOMS : 187
REMARK 3
REMARK 3 B VALUES.
REMARK 3 FROM WILSON PLOT (A**2) : NULL
REMARK 3 MEAN B VALUE (OVERALL, A**2) : 38.24
REMARK 3 OVERALL ANISOTROPIC B VALUE.
REMARK 3 B11 (A**2) : 0.86000
REMARK 3 B22 (A**2) : 0.98000
REMARK 3 B33 (A**2) : -1.85000
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): 0.259
REMARK 3 ESU BASED ON FREE R VALUE (A): 0.208
REMARK 3 ESU BASED ON MAXIMUM LIKELIHOOD (A): 0.159
REMARK 3 ESU FOR B VALUES BASED ON MAXIMUM LIKELIHOOD (A**2): 6.383
REMARK 3
REMARK 3 CORRELATION COEFFICIENTS.
REMARK 3 CORRELATION COEFFICIENT FO-FC : 0.941
REMARK 3 CORRELATION COEFFICIENT FO-FC FREE : 0.925
REMARK 3
REMARK 3 RMS DEVIATIONS FROM IDEAL VALUES COUNT RMS WEIGHT
REMARK 3 BOND LENGTHS REFINED ATOMS (A): 5013 ; 0.009 ; 0.022
REMARK 3 BOND LENGTHS OTHERS (A): 4531 ; 0.002 ; 0.020
REMARK 3 BOND ANGLES REFINED ATOMS (DEGREES): 6805 ; 1.130 ; 1.959
REMARK 3 BOND ANGLES OTHERS (DEGREES): 10450 ; 0.926 ; 3.000
REMARK 3 TORSION ANGLES, PERIOD 1 (DEGREES): 606 ; 5.700 ; 5.000
REMARK 3 TORSION ANGLES, PERIOD 2 (DEGREES): 222 ;35.434 ;23.649
REMARK 3 TORSION ANGLES, PERIOD 3 (DEGREES): 816 ;12.028 ;15.000
REMARK 3 TORSION ANGLES, PERIOD 4 (DEGREES): 24 ;18.483 ;15.000
REMARK 3 CHIRAL-CENTER RESTRAINTS (A**3): 743 ; 0.064 ; 0.200
REMARK 3 GENERAL PLANES REFINED ATOMS (A): 5538 ; 0.003 ; 0.020
REMARK 3 GENERAL PLANES OTHERS (A): 1052 ; 0.001 ; 0.020
REMARK 3 NON-BONDED CONTACTS REFINED ATOMS (A): 923 ; 0.160 ; 0.200
REMARK 3 NON-BONDED CONTACTS OTHERS (A): 4245 ; 0.128 ; 0.200
REMARK 3 NON-BONDED TORSION REFINED ATOMS (A): 2397 ; 0.159 ; 0.200
REMARK 3 NON-BONDED TORSION OTHERS (A): 2418 ; 0.075 ; 0.200
REMARK 3 H-BOND (X...Y) REFINED ATOMS (A): 206 ; 0.083 ; 0.200
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): 5 ; 0.076 ; 0.200
REMARK 3 SYMMETRY VDW OTHERS (A): 45 ; 0.169 ; 0.200
REMARK 3 SYMMETRY H-BOND REFINED ATOMS (A): 5 ; 0.103 ; 0.200
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): 3976 ; 1.600 ; 2.000
REMARK 3 MAIN-CHAIN BOND OTHER ATOMS (A**2): 1215 ; 0.260 ; 2.000
REMARK 3 MAIN-CHAIN ANGLE REFINED ATOMS (A**2): 4905 ; 1.957 ; 3.000
REMARK 3 MAIN-CHAIN ANGLE OTHER ATOMS (A**2): NULL ; NULL ; NULL
REMARK 3 SIDE-CHAIN BOND REFINED ATOMS (A**2): 2355 ; 2.687 ; 4.000
REMARK 3 SIDE-CHAIN BOND OTHER ATOMS (A**2): NULL ; NULL ; NULL
REMARK 3 SIDE-CHAIN ANGLE REFINED ATOMS (A**2): 1900 ; 3.826 ; 6.000
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 : NULL
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 ADDED IN THE RIDING
REMARK 3 POSITIONS
REMARK 4
REMARK 4 5IDN COMPLIES WITH FORMAT V. 3.30, 13-JUL-11
REMARK 100
REMARK 100 THIS ENTRY HAS BEEN PROCESSED BY PDBE ON 25-FEB-16.
REMARK 100 THE DEPOSITION ID IS D_1000218693.
REMARK 200
REMARK 200 EXPERIMENTAL DETAILS
REMARK 200 EXPERIMENT TYPE : X-RAY DIFFRACTION
REMARK 200 DATE OF DATA COLLECTION : 15-MAY-14
REMARK 200 TEMPERATURE (KELVIN) : 100
REMARK 200 PH : 6.9
REMARK 200 NUMBER OF CRYSTALS USED : 1
REMARK 200
REMARK 200 SYNCHROTRON (Y/N) : Y
REMARK 200 RADIATION SOURCE : SLS
REMARK 200 BEAMLINE : X06SA
REMARK 200 X-RAY GENERATOR MODEL : NULL
REMARK 200 MONOCHROMATIC OR LAUE (M/L) : M
REMARK 200 WAVELENGTH OR RANGE (A) : 1.00000
REMARK 200 MONOCHROMATOR : NULL
REMARK 200 OPTICS : NULL
REMARK 200
REMARK 200 DETECTOR TYPE : PIXEL
REMARK 200 DETECTOR MANUFACTURER : DECTRIS PILATUS 6M
REMARK 200 INTENSITY-INTEGRATION SOFTWARE : XDS
REMARK 200 DATA SCALING SOFTWARE : XSCALE
REMARK 200
REMARK 200 NUMBER OF UNIQUE REFLECTIONS : 40902
REMARK 200 RESOLUTION RANGE HIGH (A) : 2.260
REMARK 200 RESOLUTION RANGE LOW (A) : 84.010
REMARK 200 REJECTION CRITERIA (SIGMA(I)) : 0.000
REMARK 200
REMARK 200 OVERALL.
REMARK 200 COMPLETENESS FOR RANGE (%) : 98.2
REMARK 200 DATA REDUNDANCY : 3.700
REMARK 200 R MERGE (I) : 0.06500
REMARK 200 R SYM (I) : NULL
REMARK 200 <I/SIGMA(I)> FOR THE DATA SET : 14.9000
REMARK 200
REMARK 200 IN THE HIGHEST RESOLUTION SHELL.
REMARK 200 HIGHEST RESOLUTION SHELL, RANGE HIGH (A) : 2.26
REMARK 200 HIGHEST RESOLUTION SHELL, RANGE LOW (A) : 2.51
REMARK 200 COMPLETENESS FOR SHELL (%) : 97.8
REMARK 200 DATA REDUNDANCY IN SHELL : 3.70
REMARK 200 R MERGE FOR SHELL (I) : 0.50400
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: FOURIER SYNTHESIS
REMARK 200 SOFTWARE USED: REFMAC
REMARK 200 STARTING MODEL: 4F6S
REMARK 200
REMARK 200 REMARK: NULL
REMARK 280
REMARK 280 CRYSTAL
REMARK 280 SOLVENT CONTENT, VS (%): 59.60
REMARK 280 MATTHEWS COEFFICIENT, VM (ANGSTROMS**3/DA): 3.10
REMARK 280
REMARK 280 CRYSTALLIZATION CONDITIONS: 20% PEG 3350, 0.2 M SODIUM FORMATE, PH
REMARK 280 6.9, VAPOR DIFFUSION, HANGING DROP, TEMPERATURE 293K
REMARK 290
REMARK 290 CRYSTALLOGRAPHIC SYMMETRY
REMARK 290 SYMMETRY OPERATORS FOR SPACE GROUP: P 21 21 21
REMARK 290
REMARK 290 SYMOP SYMMETRY
REMARK 290 NNNMMM OPERATOR
REMARK 290 1555 X,Y,Z
REMARK 290 2555 -X+1/2,-Y,Z+1/2
REMARK 290 3555 -X,Y+1/2,-Z+1/2
REMARK 290 4555 X+1/2,-Y+1/2,-Z
REMARK 290
REMARK 290 WHERE NNN -> OPERATOR NUMBER
REMARK 290 MMM -> TRANSLATION VECTOR
REMARK 290
REMARK 290 CRYSTALLOGRAPHIC SYMMETRY TRANSFORMATIONS
REMARK 290 THE FOLLOWING TRANSFORMATIONS OPERATE ON THE ATOM/HETATM
REMARK 290 RECORDS IN THIS ENTRY TO PRODUCE CRYSTALLOGRAPHICALLY
REMARK 290 RELATED MOLECULES.
REMARK 290 SMTRY1 1 1.000000 0.000000 0.000000 0.00000
REMARK 290 SMTRY2 1 0.000000 1.000000 0.000000 0.00000
REMARK 290 SMTRY3 1 0.000000 0.000000 1.000000 0.00000
REMARK 290 SMTRY1 2 -1.000000 0.000000 0.000000 35.23000
REMARK 290 SMTRY2 2 0.000000 -1.000000 0.000000 0.00000
REMARK 290 SMTRY3 2 0.000000 0.000000 1.000000 84.01000
REMARK 290 SMTRY1 3 -1.000000 0.000000 0.000000 0.00000
REMARK 290 SMTRY2 3 0.000000 1.000000 0.000000 36.73350
REMARK 290 SMTRY3 3 0.000000 0.000000 -1.000000 84.01000
REMARK 290 SMTRY1 4 1.000000 0.000000 0.000000 35.23000
REMARK 290 SMTRY2 4 0.000000 -1.000000 0.000000 36.73350
REMARK 290 SMTRY3 4 0.000000 0.000000 -1.000000 0.00000
REMARK 290
REMARK 290 REMARK: NULL
REMARK 300
REMARK 300 BIOMOLECULE: 1
REMARK 300 SEE REMARK 350 FOR THE AUTHOR PROVIDED AND/OR PROGRAM
REMARK 300 GENERATED ASSEMBLY INFORMATION FOR THE STRUCTURE IN
REMARK 300 THIS ENTRY. THE REMARK MAY ALSO PROVIDE INFORMATION ON
REMARK 300 BURIED SURFACE AREA.
REMARK 350
REMARK 350 COORDINATES FOR A COMPLETE MULTIMER REPRESENTING THE KNOWN
REMARK 350 BIOLOGICALLY SIGNIFICANT OLIGOMERIZATION STATE OF THE
REMARK 350 MOLECULE CAN BE GENERATED BY APPLYING BIOMT TRANSFORMATIONS
REMARK 350 GIVEN BELOW. BOTH NON-CRYSTALLOGRAPHIC AND
REMARK 350 CRYSTALLOGRAPHIC OPERATIONS ARE GIVEN.
REMARK 350
REMARK 350 BIOMOLECULE: 1
REMARK 350 SOFTWARE DETERMINED QUATERNARY STRUCTURE: DIMERIC
REMARK 350 SOFTWARE USED: PISA
REMARK 350 TOTAL BURIED SURFACE AREA: 4600 ANGSTROM**2
REMARK 350 SURFACE AREA OF THE COMPLEX: 29060 ANGSTROM**2
REMARK 350 CHANGE IN SOLVENT FREE ENERGY: -22.0 KCAL/MOL
REMARK 350 APPLY THE FOLLOWING TO CHAINS: A, B
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 ASP A -1
REMARK 465 LYS A 0
REMARK 465 LYS A 118
REMARK 465 LYS A 119
REMARK 465 PRO A 120
REMARK 465 VAL A 121
REMARK 465 GLN A 122
REMARK 465 LEU A 179
REMARK 465 PHE A 180
REMARK 465 ASN A 181
REMARK 465 SER A 182
REMARK 465 PRO A 183
REMARK 465 LEU A 184
REMARK 465 LYS A 185
REMARK 465 PRO A 186
REMARK 465 LEU A 187
REMARK 465 ALA A 188
REMARK 465 ASP A 189
REMARK 465 LEU A 190
REMARK 465 ASP A 191
REMARK 465 PRO A 192
REMARK 465 VAL A 193
REMARK 465 VAL A 194
REMARK 465 GLU A 239
REMARK 465 ASP A 240
REMARK 465 ILE A 241
REMARK 465 LYS A 242
REMARK 465 THR A 243
REMARK 465 SER A 244
REMARK 465 PRO A 364
REMARK 465 PRO A 365
REMARK 465 LEU A 366
REMARK 465 LYS A 367
REMARK 465 LYS A 368
REMARK 480
REMARK 480 ZERO OCCUPANCY ATOM
REMARK 480 THE FOLLOWING RESIDUES HAVE ATOMS MODELED WITH ZERO
REMARK 480 OCCUPANCY. THE LOCATION AND PROPERTIES OF THESE ATOMS
REMARK 480 MAY NOT BE RELIABLE. (M=MODEL NUMBER; RES=RESIDUE NAME;
REMARK 480 C=CHAIN IDENTIFIER; SSEQ=SEQUENCE NUMBER; I=INSERTION CODE):
REMARK 480 M RES C SSEQI ATOMS
REMARK 480 LYS A 6 CD CE NZ
REMARK 480 LYS A 8 CE NZ
REMARK 480 GLU A 23 CG CD OE1 OE2
REMARK 480 LYS A 39 CE NZ
REMARK 480 ARG A 40 NE CZ NH1 NH2
REMARK 480 ASP A 42 CG OD1 OD2
REMARK 480 LYS A 44 CG CD CE NZ
REMARK 480 ASP A 46 CG OD1 OD2
REMARK 480 LYS A 47 CG CD CE NZ
REMARK 480 LYS A 74 CE NZ
REMARK 480 LYS A 83 CE NZ
REMARK 480 LYS A 109 CD CE NZ
REMARK 480 ARG A 112 CZ NH1 NH2
REMARK 480 SER A 114 OG
REMARK 480 LYS A 115 CG CD CE NZ
REMARK 480 ASN A 117 CG OD1 ND2
REMARK 480 LEU A 123 CG CD1 CD2
REMARK 480 ARG A 178 CG CD NE CZ NH1 NH2
REMARK 480 ARG A 209 NE CZ NH1 NH2
REMARK 480 ARG A 237 CG CD NE CZ NH1 NH2
REMARK 480 GLN A 238 CG CD OE1 NE2
REMARK 480 ASN A 245 CG OD1 ND2
REMARK 480 LYS A 265 CG CD CE NZ
REMARK 480 LYS A 271 CD CE NZ
REMARK 480 LYS A 272 CE NZ
REMARK 480 LYS A 281 CD CE NZ
REMARK 480 ARG A 284 CZ NH1 NH2
REMARK 480 ARG A 285 CG CD NE CZ NH1 NH2
REMARK 480 LYS A 295 CE NZ
REMARK 480 LYS A 301 CD CE NZ
REMARK 480 LYS A 303 CD CE NZ
REMARK 480 GLU A 327 CD OE1 OE2
REMARK 480 GLN A 350 CG CD OE1 NE2
REMARK 480 LYS A 355 CE NZ
REMARK 480 GLU A 357 CG CD OE1 OE2
REMARK 480 GLU A 363 CG CD OE1 OE2
REMARK 480 LYS B -1 CE NZ
REMARK 480 LYS B 18 CD CE NZ
REMARK 480 LEU B 22 CG CD1 CD2
REMARK 480 LYS B 23 CD CE NZ
REMARK 480 LYS B 27 CG CD CE NZ
REMARK 480 LYS B 30 CE NZ
REMARK 480 GLU B 35 CD OE1 OE2
REMARK 480 LYS B 56 CD CE NZ
REMARK 480 ARG B 58 CD NE CZ NH1 NH2
REMARK 480 GLN B 60 CG CD OE1 NE2
REMARK 480 ARG B 75 CD NE CZ NH1 NH2
REMARK 480 LYS B 117 CD CE NZ
REMARK 480 LYS B 126 CE NZ
REMARK 480 GLU B 127 CD OE1 OE2
REMARK 480 ARG B 131 CD NE CZ NH1 NH2
REMARK 480 LEU B 145 CG CD1 CD2
REMARK 480 ARG B 157 NE CZ NH1 NH2
REMARK 480 GLU B 169 CD OE1 OE2
REMARK 480 LYS B 211 CD CE NZ
REMARK 480 ARG B 214 CG CD NE CZ NH1 NH2
REMARK 480 SER B 221 OG
REMARK 480 LYS B 226 CD CE NZ
REMARK 480 LYS B 236 CD CE NZ
REMARK 480 LYS B 256 CE NZ
REMARK 480 LYS B 259 CG CD CE NZ
REMARK 480 LYS B 261 CE NZ
REMARK 500
REMARK 500 GEOMETRY AND STEREOCHEMISTRY
REMARK 500 SUBTOPIC: COVALENT BOND LENGTHS
REMARK 500
REMARK 500 THE STEREOCHEMICAL PARAMETERS OF THE FOLLOWING RESIDUES
REMARK 500 HAVE VALUES WHICH DEVIATE FROM EXPECTED VALUES BY MORE
REMARK 500 THAN 6*RMSD (M=MODEL NUMBER; RES=RESIDUE NAME; C=CHAIN
REMARK 500 IDENTIFIER; SSEQ=SEQUENCE NUMBER; I=INSERTION CODE).
REMARK 500
REMARK 500 STANDARD TABLE:
REMARK 500 FORMAT: (10X,I3,1X,2(A3,1X,A1,I4,A1,1X,A4,3X),1X,F6.3)
REMARK 500
REMARK 500 EXPECTED VALUES PROTEIN: ENGH AND HUBER, 1999
REMARK 500 EXPECTED VALUES NUCLEIC ACID: CLOWNEY ET AL 1996
REMARK 500
REMARK 500 M RES CSSEQI ATM1 RES CSSEQI ATM2 DEVIATION
REMARK 500 ARG A 284 NE ARG A 284 CZ 0.103
REMARK 500
REMARK 500 REMARK: NULL
REMARK 500
REMARK 500 GEOMETRY AND STEREOCHEMISTRY
REMARK 500 SUBTOPIC: COVALENT BOND ANGLES
REMARK 500
REMARK 500 THE STEREOCHEMICAL PARAMETERS OF THE FOLLOWING RESIDUES
REMARK 500 HAVE VALUES WHICH DEVIATE FROM EXPECTED VALUES BY MORE
REMARK 500 THAN 6*RMSD (M=MODEL NUMBER; RES=RESIDUE NAME; C=CHAIN
REMARK 500 IDENTIFIER; SSEQ=SEQUENCE NUMBER; I=INSERTION CODE).
REMARK 500
REMARK 500 STANDARD TABLE:
REMARK 500 FORMAT: (10X,I3,1X,A3,1X,A1,I4,A1,3(1X,A4,2X),12X,F5.1)
REMARK 500
REMARK 500 EXPECTED VALUES PROTEIN: ENGH AND HUBER, 1999
REMARK 500 EXPECTED VALUES NUCLEIC ACID: CLOWNEY ET AL 1996
REMARK 500
REMARK 500 M RES CSSEQI ATM1 ATM2 ATM3
REMARK 500 ARG A 284 NE - CZ - NH1 ANGL. DEV. = 4.0 DEGREES
REMARK 500 ARG A 284 NE - CZ - NH2 ANGL. DEV. = -3.2 DEGREES
REMARK 500
REMARK 500 REMARK: NULL
REMARK 500
REMARK 500 GEOMETRY AND STEREOCHEMISTRY
REMARK 500 SUBTOPIC: TORSION ANGLES
REMARK 500
REMARK 500 TORSION ANGLES OUTSIDE THE EXPECTED RAMACHANDRAN REGIONS:
REMARK 500 (M=MODEL NUMBER; RES=RESIDUE NAME; C=CHAIN IDENTIFIER;
REMARK 500 SSEQ=SEQUENCE NUMBER; I=INSERTION CODE).
REMARK 500
REMARK 500 STANDARD TABLE:
REMARK 500 FORMAT:(10X,I3,1X,A3,1X,A1,I4,A1,4X,F7.2,3X,F7.2)
REMARK 500
REMARK 500 EXPECTED VALUES: GJ KLEYWEGT AND TA JONES (1996). PHI/PSI-
REMARK 500 CHOLOGY: RAMACHANDRAN REVISITED. STRUCTURE 4, 1395 - 1400
REMARK 500
REMARK 500 M RES CSSEQI PSI PHI
REMARK 500 ARG A 150 -0.94 80.54
REMARK 500 ASP A 151 55.89 -161.67
REMARK 500 ARG A 166 120.65 -39.46
REMARK 500 ASP A 173 75.48 67.51
REMARK 500 PHE A 234 41.68 -108.83
REMARK 500 LEU A 316 59.61 -94.74
REMARK 500 PHE B 128 109.79 -54.70
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 6A7 A 401
REMARK 800
REMARK 800 SITE_IDENTIFIER: AC2
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: binding site for residue EDO A 402
REMARK 800
REMARK 800 SITE_IDENTIFIER: AC3
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: binding site for residue FMT A 403
REMARK 800
REMARK 800 SITE_IDENTIFIER: AC4
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: binding site for residue FMT A 404
REMARK 800
REMARK 800 SITE_IDENTIFIER: AC5
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: binding site for residue FMT A 405
REMARK 800
REMARK 800 SITE_IDENTIFIER: AC6
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: binding site for residue FMT B 301
REMARK 800
REMARK 800 SITE_IDENTIFIER: AC7
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: binding site for residue FMT B 302
REMARK 800
REMARK 800 SITE_IDENTIFIER: AC8
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: binding site for residue FMT B 303
DBREF 5IDN A 1 364 UNP P49336 CDK8_HUMAN 1 364
DBREF 5IDN B 1 264 UNP P24863 CCNC_HUMAN 1 264
SEQADV 5IDN ASP A -1 UNP P49336 EXPRESSION TAG
SEQADV 5IDN LYS A 0 UNP P49336 EXPRESSION TAG
SEQADV 5IDN PRO A 365 UNP P49336 EXPRESSION TAG
SEQADV 5IDN LEU A 366 UNP P49336 EXPRESSION TAG
SEQADV 5IDN LYS A 367 UNP P49336 EXPRESSION TAG
SEQADV 5IDN LYS A 368 UNP P49336 EXPRESSION TAG
SEQADV 5IDN ASP B -2 UNP P24863 EXPRESSION TAG
SEQADV 5IDN LYS B -1 UNP P24863 EXPRESSION TAG
SEQADV 5IDN ALA B 0 UNP P24863 EXPRESSION TAG
SEQRES 1 A 370 ASP LYS MET ASP TYR ASP PHE LYS VAL LYS LEU SER SER
SEQRES 2 A 370 GLU ARG GLU ARG VAL GLU ASP LEU PHE GLU TYR GLU GLY
SEQRES 3 A 370 CYS LYS VAL GLY ARG GLY THR TYR GLY HIS VAL TYR LYS
SEQRES 4 A 370 ALA LYS ARG LYS ASP GLY LYS ASP ASP LYS ASP TYR ALA
SEQRES 5 A 370 LEU LYS GLN ILE GLU GLY THR GLY ILE SER MET SER ALA
SEQRES 6 A 370 CYS ARG GLU ILE ALA LEU LEU ARG GLU LEU LYS HIS PRO
SEQRES 7 A 370 ASN VAL ILE SER LEU GLN LYS VAL PHE LEU SER HIS ALA
SEQRES 8 A 370 ASP ARG LYS VAL TRP LEU LEU PHE ASP TYR ALA GLU HIS
SEQRES 9 A 370 ASP LEU TRP HIS ILE ILE LYS PHE HIS ARG ALA SER LYS
SEQRES 10 A 370 ALA ASN LYS LYS PRO VAL GLN LEU PRO ARG GLY MET VAL
SEQRES 11 A 370 LYS SER LEU LEU TYR GLN ILE LEU ASP GLY ILE HIS TYR
SEQRES 12 A 370 LEU HIS ALA ASN TRP VAL LEU HIS ARG ASP LEU LYS PRO
SEQRES 13 A 370 ALA ASN ILE LEU VAL MET GLY GLU GLY PRO GLU ARG GLY
SEQRES 14 A 370 ARG VAL LYS ILE ALA ASP MET GLY PHE ALA ARG LEU PHE
SEQRES 15 A 370 ASN SER PRO LEU LYS PRO LEU ALA ASP LEU ASP PRO VAL
SEQRES 16 A 370 VAL VAL THR PHE TRP TYR ARG ALA PRO GLU LEU LEU LEU
SEQRES 17 A 370 GLY ALA ARG HIS TYR THR LYS ALA ILE ASP ILE TRP ALA
SEQRES 18 A 370 ILE GLY CYS ILE PHE ALA GLU LEU LEU THR SER GLU PRO
SEQRES 19 A 370 ILE PHE HIS CYS ARG GLN GLU ASP ILE LYS THR SER ASN
SEQRES 20 A 370 PRO TYR HIS HIS ASP GLN LEU ASP ARG ILE PHE ASN VAL
SEQRES 21 A 370 MET GLY PHE PRO ALA ASP LYS ASP TRP GLU ASP ILE LYS
SEQRES 22 A 370 LYS MET PRO GLU HIS SER THR LEU MET LYS ASP PHE ARG
SEQRES 23 A 370 ARG ASN THR TYR THR ASN CYS SER LEU ILE LYS TYR MET
SEQRES 24 A 370 GLU LYS HIS LYS VAL LYS PRO ASP SER LYS ALA PHE HIS
SEQRES 25 A 370 LEU LEU GLN LYS LEU LEU THR MET ASP PRO ILE LYS ARG
SEQRES 26 A 370 ILE THR SER GLU GLN ALA MET GLN ASP PRO TYR PHE LEU
SEQRES 27 A 370 GLU ASP PRO LEU PRO THR SER ASP VAL PHE ALA GLY CYS
SEQRES 28 A 370 GLN ILE PRO TYR PRO LYS ARG GLU PHE LEU THR GLU GLU
SEQRES 29 A 370 GLU PRO PRO LEU LYS LYS
SEQRES 1 B 267 ASP LYS ALA MET ALA GLY ASN PHE TRP GLN SER SER HIS
SEQRES 2 B 267 TYR LEU GLN TRP ILE LEU ASP LYS GLN ASP LEU LEU LYS
SEQRES 3 B 267 GLU ARG GLN LYS ASP LEU LYS PHE LEU SER GLU GLU GLU
SEQRES 4 B 267 TYR TRP LYS LEU GLN ILE PHE PHE THR ASN VAL ILE GLN
SEQRES 5 B 267 ALA LEU GLY GLU HIS LEU LYS LEU ARG GLN GLN VAL ILE
SEQRES 6 B 267 ALA THR ALA THR VAL TYR PHE LYS ARG PHE TYR ALA ARG
SEQRES 7 B 267 TYR SER LEU LYS SER ILE ASP PRO VAL LEU MET ALA PRO
SEQRES 8 B 267 THR CYS VAL PHE LEU ALA SER LYS VAL GLU GLU PHE GLY
SEQRES 9 B 267 VAL VAL SER ASN THR ARG LEU ILE ALA ALA ALA THR SER
SEQRES 10 B 267 VAL LEU LYS THR ARG PHE SER TYR ALA PHE PRO LYS GLU
SEQRES 11 B 267 PHE PRO TYR ARG MET ASN HIS ILE LEU GLU CYS GLU PHE
SEQRES 12 B 267 TYR LEU LEU GLU LEU MET ASP CYS CYS LEU ILE VAL TYR
SEQRES 13 B 267 HIS PRO TYR ARG PRO LEU LEU GLN TYR VAL GLN ASP MET
SEQRES 14 B 267 GLY GLN GLU ASP MET LEU LEU PRO LEU ALA TRP ARG ILE
SEQRES 15 B 267 VAL ASN ASP THR TYR ARG THR ASP LEU CYS LEU LEU TYR
SEQRES 16 B 267 PRO PRO PHE MET ILE ALA LEU ALA CYS LEU HIS VAL ALA
SEQRES 17 B 267 CYS VAL VAL GLN GLN LYS ASP ALA ARG GLN TRP PHE ALA
SEQRES 18 B 267 GLU LEU SER VAL ASP MET GLU LYS ILE LEU GLU ILE ILE
SEQRES 19 B 267 ARG VAL ILE LEU LYS LEU TYR GLU GLN TRP LYS ASN PHE
SEQRES 20 B 267 ASP GLU ARG LYS GLU MET ALA THR ILE LEU SER LYS MET
SEQRES 21 B 267 PRO LYS PRO LYS PRO PRO PRO
HET 6A7 A 401 24
HET EDO A 402 4
HET FMT A 403 3
HET FMT A 404 3
HET FMT A 405 3
HET FMT B 301 3
HET FMT B 302 3
HET FMT B 303 3
HETNAM 6A7 [(2S)-2-(4-CHLOROPHENYL)PYRROLIDIN-1-YL](3-METHYL-1H-
HETNAM 2 6A7 PYRAZOLO[3,4-B]PYRIDIN-5-YL)METHANONE
HETNAM EDO 1,2-ETHANEDIOL
HETNAM FMT FORMIC ACID
HETSYN EDO ETHYLENE GLYCOL
FORMUL 3 6A7 C18 H17 CL N4 O
FORMUL 4 EDO C2 H6 O2
FORMUL 5 FMT 6(C H2 O2)
FORMUL 11 HOH *187(H2 O)
HELIX 1 AA1 ASP A 2 ARG A 13 1 12
HELIX 2 AA2 ARG A 15 LEU A 19 1 5
HELIX 3 AA3 SER A 60 LEU A 73 1 14
HELIX 4 AA4 LEU A 104 LYS A 115 1 12
HELIX 5 AA5 PRO A 124 ASN A 145 1 22
HELIX 6 AA6 LYS A 153 ALA A 155 5 3
HELIX 7 AA7 ALA A 201 LEU A 206 1 6
HELIX 8 AA8 THR A 212 SER A 230 1 19
HELIX 9 AA9 HIS A 248 GLY A 260 1 13
HELIX 10 AB1 TRP A 267 MET A 273 5 7
HELIX 11 AB2 GLU A 275 PHE A 283 1 9
HELIX 12 AB3 ARG A 284 THR A 289 5 6
HELIX 13 AB4 SER A 292 HIS A 300 1 9
HELIX 14 AB5 SER A 306 LEU A 316 1 11
HELIX 15 AB6 ASP A 319 ARG A 323 5 5
HELIX 16 AB7 THR A 325 GLN A 331 1 7
HELIX 17 AB8 ASP A 332 LEU A 336 5 5
HELIX 18 AB9 ASN B 4 GLN B 7 5 4
HELIX 19 AC1 SER B 8 ILE B 15 1 8
HELIX 20 AC2 ASP B 17 GLN B 26 1 10
HELIX 21 AC3 SER B 33 LEU B 55 1 23
HELIX 22 AC4 ARG B 58 TYR B 76 1 19
HELIX 23 AC5 ASP B 82 GLU B 98 1 17
HELIX 24 AC6 SER B 104 ARG B 119 1 16
HELIX 25 AC7 ARG B 131 MET B 146 1 16
HELIX 26 AC8 PRO B 155 GLY B 167 1 13
HELIX 27 AC9 GLN B 168 TYR B 184 1 17
HELIX 28 AD1 ASP B 187 TYR B 192 1 6
HELIX 29 AD2 PRO B 193 GLN B 209 1 17
HELIX 30 AD3 ALA B 213 GLU B 219 1 7
HELIX 31 AD4 ASP B 223 PHE B 244 1 22
HELIX 32 AD5 ASP B 245 LYS B 256 1 12
SHEET 1 AA1 3 PHE A 20 GLU A 21 0
SHEET 2 AA1 3 GLY A 33 ARG A 40 -1 O LYS A 39 N GLU A 21
SHEET 3 AA1 3 LYS A 26 GLY A 30 -1 N VAL A 27 O VAL A 35
SHEET 1 AA2 5 PHE A 20 GLU A 21 0
SHEET 2 AA2 5 GLY A 33 ARG A 40 -1 O LYS A 39 N GLU A 21
SHEET 3 AA2 5 TYR A 49 ILE A 54 -1 O GLN A 53 N HIS A 34
SHEET 4 AA2 5 LYS A 92 ASP A 98 -1 O PHE A 97 N ALA A 50
SHEET 5 AA2 5 LEU A 81 SER A 87 -1 N GLN A 82 O LEU A 96
SHEET 1 AA3 3 HIS A 102 ASP A 103 0
SHEET 2 AA3 3 ILE A 157 VAL A 159 -1 O VAL A 159 N HIS A 102
SHEET 3 AA3 3 VAL A 169 ILE A 171 -1 O LYS A 170 N LEU A 158
CISPEP 1 ASP A 338 PRO A 339 0 -6.32
SITE 1 AC1 14 VAL A 27 GLY A 28 TYR A 32 ALA A 50
SITE 2 AC1 14 LYS A 52 ILE A 79 PHE A 97 ASP A 98
SITE 3 AC1 14 TYR A 99 ALA A 100 ALA A 155 LEU A 158
SITE 4 AC1 14 ASP A 173 ARG A 356
SITE 1 AC2 3 ARG A 125 VAL A 302 LYS A 303
SITE 1 AC3 4 HIS A 149 ASP A 151 ASP A 173 PHE A 176
SITE 1 AC4 4 TYR A 32 LYS A 52 SER A 62 ALA A 63
SITE 1 AC5 5 GLU A 17 TYR A 22 SER A 87 ASP A 90
SITE 2 AC5 5 TRP A 94
SITE 1 AC6 6 ALA B 2 GLY B 3 TYR B 153 ARG B 157
SITE 2 AC6 6 FMT B 302 HOH B 414
SITE 1 AC7 4 ALA B 0 TYR B 153 FMT B 301 HOH B 437
SITE 1 AC8 5 HIS B 203 LYS B 211 ASP B 212 ALA B 213
SITE 2 AC8 5 ARG B 214
CRYST1 70.460 73.467 168.020 90.00 90.00 90.00 P 21 21 21 4
ORIGX1 1.000000 0.000000 0.000000 0.00000
ORIGX2 0.000000 1.000000 0.000000 0.00000
ORIGX3 0.000000 0.000000 1.000000 0.00000
SCALE1 0.014192 0.000000 0.000000 0.00000
SCALE2 0.000000 0.013612 0.000000 0.00000
SCALE3 0.000000 0.000000 0.005952 0.00000
(ATOM LINES ARE NOT SHOWN.)
END
