HEADER TRANSFERASE 11-FEB-13 3ZMM
TITLE INHIBITORS OF JAK2 KINASE DOMAIN
COMPND MOL_ID: 1;
COMPND 2 MOLECULE: TYROSINE-PROTEIN KINASE JAK2;
COMPND 3 CHAIN: A, B;
COMPND 4 FRAGMENT: KINASE DOMAIN, RESIDUES 835-1132;
COMPND 5 SYNONYM: JANUS KINASE 2, JAK-2;
COMPND 6 EC: 2.7.10.2, 2.7.1.112;
COMPND 7 ENGINEERED: YES;
COMPND 8 MUTATION: 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: STAR;
SOURCE 9 EXPRESSION_SYSTEM_VECTOR_TYPE: PLASMID;
SOURCE 10 EXPRESSION_SYSTEM_VECTOR: PT7 3.3
KEYWDS TRANSFERASE
EXPDTA X-RAY DIFFRACTION
AUTHOR J.READ,I.GREEN,H.POLLARD,T.HOWARD,R.MOTT
REVDAT 4 20-DEC-23 3ZMM 1 REMARK LINK
REVDAT 3 28-JUN-17 3ZMM 1 REMARK
REVDAT 2 08-MAY-13 3ZMM 1 SOURCE JRNL
REVDAT 1 17-APR-13 3ZMM 0
JRNL AUTH H.GUAN,M.L.LAMB,B.PENG,S.HUANG,N.DEGRACE,J.READ,S.HUSSAIN,
JRNL AUTH 2 J.WU,C.RIVARD,M.ALIMZHANOV,G.BEBERNITZ,K.BELL,M.YE,M.ZINDA,
JRNL AUTH 3 S.IOANNIDIS
JRNL TITL DISCOVERY OF NOVEL JAK2-STAT PATHWAY INHIBITORS WITH
JRNL TITL 2 EXTENDED RESIDENCE TIME ON TARGET.
JRNL REF BIOORG.MED.CHEM.LETT. V. 23 3105 2013
JRNL REFN ISSN 0960-894X
JRNL PMID 23562594
JRNL DOI 10.1016/J.BMCL.2013.02.111
REMARK 2
REMARK 2 RESOLUTION. 2.51 ANGSTROMS.
REMARK 3
REMARK 3 REFINEMENT.
REMARK 3 PROGRAM : REFMAC 5.6.0117
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) : 2.51
REMARK 3 RESOLUTION RANGE LOW (ANGSTROMS) : 17.57
REMARK 3 DATA CUTOFF (SIGMA(F)) : NULL
REMARK 3 COMPLETENESS FOR RANGE (%) : 95.6
REMARK 3 NUMBER OF REFLECTIONS : 23024
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) : 0.195
REMARK 3 R VALUE (WORKING SET) : 0.193
REMARK 3 FREE R VALUE : 0.246
REMARK 3 FREE R VALUE TEST SET SIZE (%) : 5.100
REMARK 3 FREE R VALUE TEST SET COUNT : 1239
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) : 2.51
REMARK 3 BIN RESOLUTION RANGE LOW (A) : 2.58
REMARK 3 REFLECTION IN BIN (WORKING SET) : 1365
REMARK 3 BIN COMPLETENESS (WORKING+TEST) (%) : 79.04
REMARK 3 BIN R VALUE (WORKING SET) : 0.4910
REMARK 3 BIN FREE R VALUE SET COUNT : 72
REMARK 3 BIN FREE R VALUE : 0.5970
REMARK 3
REMARK 3 NUMBER OF NON-HYDROGEN ATOMS USED IN REFINEMENT.
REMARK 3 PROTEIN ATOMS : 4495
REMARK 3 NUCLEIC ACID ATOMS : 0
REMARK 3 HETEROGEN ATOMS : 69
REMARK 3 SOLVENT ATOMS : 140
REMARK 3
REMARK 3 B VALUES.
REMARK 3 FROM WILSON PLOT (A**2) : NULL
REMARK 3 MEAN B VALUE (OVERALL, A**2) : 62.23
REMARK 3 OVERALL ANISOTROPIC B VALUE.
REMARK 3 B11 (A**2) : 0.92000
REMARK 3 B22 (A**2) : 0.02000
REMARK 3 B33 (A**2) : -0.92000
REMARK 3 B12 (A**2) : 0.00000
REMARK 3 B13 (A**2) : 0.08000
REMARK 3 B23 (A**2) : 0.00000
REMARK 3
REMARK 3 ESTIMATED OVERALL COORDINATE ERROR.
REMARK 3 ESU BASED ON R VALUE (A): 0.534
REMARK 3 ESU BASED ON FREE R VALUE (A): 0.289
REMARK 3 ESU BASED ON MAXIMUM LIKELIHOOD (A): 0.218
REMARK 3 ESU FOR B VALUES BASED ON MAXIMUM LIKELIHOOD (A**2): 19.256
REMARK 3
REMARK 3 CORRELATION COEFFICIENTS.
REMARK 3 CORRELATION COEFFICIENT FO-FC : 0.948
REMARK 3 CORRELATION COEFFICIENT FO-FC FREE : 0.921
REMARK 3
REMARK 3 RMS DEVIATIONS FROM IDEAL VALUES COUNT RMS WEIGHT
REMARK 3 BOND LENGTHS REFINED ATOMS (A): 4681 ; 0.009 ; 0.019
REMARK 3 BOND LENGTHS OTHERS (A): 3196 ; 0.001 ; 0.020
REMARK 3 BOND ANGLES REFINED ATOMS (DEGREES): 6322 ; 1.460 ; 1.996
REMARK 3 BOND ANGLES OTHERS (DEGREES): 7758 ; 0.887 ; 3.000
REMARK 3 TORSION ANGLES, PERIOD 1 (DEGREES): 550 ; 6.291 ; 5.000
REMARK 3 TORSION ANGLES, PERIOD 2 (DEGREES): 226 ;38.693 ;23.982
REMARK 3 TORSION ANGLES, PERIOD 3 (DEGREES): 828 ;17.551 ;15.000
REMARK 3 TORSION ANGLES, PERIOD 4 (DEGREES): 34 ;19.378 ;15.000
REMARK 3 CHIRAL-CENTER RESTRAINTS (A**3): 670 ; 0.077 ; 0.200
REMARK 3 GENERAL PLANES REFINED ATOMS (A): 5185 ; 0.005 ; 0.021
REMARK 3 GENERAL PLANES OTHERS (A): 955 ; 0.001 ; 0.020
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 : 2
REMARK 3
REMARK 3 TLS GROUP : 1
REMARK 3 NUMBER OF COMPONENTS GROUP : 1
REMARK 3 COMPONENTS C SSSEQI TO C SSSEQI
REMARK 3 RESIDUE RANGE : A 844 A 1130
REMARK 3 ORIGIN FOR THE GROUP (A): 5.7562 13.0953 21.7308
REMARK 3 T TENSOR
REMARK 3 T11: 0.2060 T22: 0.1988
REMARK 3 T33: 0.0597 T12: -0.0607
REMARK 3 T13: 0.0437 T23: 0.0486
REMARK 3 L TENSOR
REMARK 3 L11: 0.6113 L22: 2.0251
REMARK 3 L33: 1.9228 L12: 0.0202
REMARK 3 L13: -0.0021 L23: -0.6656
REMARK 3 S TENSOR
REMARK 3 S11: 0.0868 S12: 0.0820 S13: 0.0315
REMARK 3 S21: -0.1913 S22: -0.3763 S23: -0.1482
REMARK 3 S31: -0.0488 S32: 0.3239 S33: 0.2896
REMARK 3
REMARK 3 TLS GROUP : 2
REMARK 3 NUMBER OF COMPONENTS GROUP : 1
REMARK 3 COMPONENTS C SSSEQI TO C SSSEQI
REMARK 3 RESIDUE RANGE : B 843 B 1131
REMARK 3 ORIGIN FOR THE GROUP (A): 23.7022 -12.5842 46.3797
REMARK 3 T TENSOR
REMARK 3 T11: 0.2593 T22: 0.1737
REMARK 3 T33: 0.0209 T12: -0.1055
REMARK 3 T13: 0.0210 T23: 0.0341
REMARK 3 L TENSOR
REMARK 3 L11: 1.0584 L22: 0.9956
REMARK 3 L33: 0.9829 L12: -0.1770
REMARK 3 L13: -0.1310 L23: 0.2201
REMARK 3 S TENSOR
REMARK 3 S11: -0.1192 S12: 0.0076 S13: -0.0220
REMARK 3 S21: 0.0023 S22: 0.0463 S23: 0.0008
REMARK 3 S31: 0.1792 S32: -0.0806 S33: 0.0729
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 ADDED IN THE RIDING
REMARK 3 POSITIONS.
REMARK 4
REMARK 4 3ZMM COMPLIES WITH FORMAT V. 3.30, 13-JUL-11
REMARK 100
REMARK 100 THIS ENTRY HAS BEEN PROCESSED BY PDBE ON 11-FEB-13.
REMARK 100 THE DEPOSITION ID IS D_1290055786.
REMARK 200
REMARK 200 EXPERIMENTAL DETAILS
REMARK 200 EXPERIMENT TYPE : X-RAY DIFFRACTION
REMARK 200 DATE OF DATA COLLECTION : 21-DEC-07
REMARK 200 TEMPERATURE (KELVIN) : 100
REMARK 200 PH : 7.4
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
REMARK 200 MONOCHROMATIC OR LAUE (M/L) : M
REMARK 200 WAVELENGTH OR RANGE (A) : 1.5418
REMARK 200 MONOCHROMATOR : NI FILTER
REMARK 200 OPTICS : MIRRORS
REMARK 200
REMARK 200 DETECTOR TYPE : IMAGE PLATE
REMARK 200 DETECTOR MANUFACTURER : MAR SCANNER 345 MM PLATE
REMARK 200 INTENSITY-INTEGRATION SOFTWARE : MOSFLM
REMARK 200 DATA SCALING SOFTWARE : SCALEPACK
REMARK 200
REMARK 200 NUMBER OF UNIQUE REFLECTIONS : 24425
REMARK 200 RESOLUTION RANGE HIGH (A) : 2.500
REMARK 200 RESOLUTION RANGE LOW (A) : 17.570
REMARK 200 REJECTION CRITERIA (SIGMA(I)) : 2.000
REMARK 200
REMARK 200 OVERALL.
REMARK 200 COMPLETENESS FOR RANGE (%) : 95.0
REMARK 200 DATA REDUNDANCY : 6.600
REMARK 200 R MERGE (I) : 0.06000
REMARK 200 R SYM (I) : NULL
REMARK 200 <I/SIGMA(I)> FOR THE DATA SET : 6.4800
REMARK 200
REMARK 200 IN THE HIGHEST RESOLUTION SHELL.
REMARK 200 HIGHEST RESOLUTION SHELL, RANGE HIGH (A) : 2.50
REMARK 200 HIGHEST RESOLUTION SHELL, RANGE LOW (A) : 2.64
REMARK 200 COMPLETENESS FOR SHELL (%) : 83.2
REMARK 200 DATA REDUNDANCY IN SHELL : 5.85
REMARK 200 R MERGE FOR SHELL (I) : 0.30000
REMARK 200 R SYM FOR SHELL (I) : NULL
REMARK 200 <I/SIGMA(I)> FOR SHELL : 2.350
REMARK 200
REMARK 200 DIFFRACTION PROTOCOL: SINGLE WAVELENGTH
REMARK 200 METHOD USED TO DETERMINE THE STRUCTURE: MOLECULAR REPLACEMENT
REMARK 200 SOFTWARE USED: AMORE
REMARK 200 STARTING MODEL: PDB ENTRY 2XA4
REMARK 200
REMARK 200 REMARK: NONE
REMARK 280
REMARK 280 CRYSTAL
REMARK 280 SOLVENT CONTENT, VS (%): 54.47
REMARK 280 MATTHEWS COEFFICIENT, VM (ANGSTROMS**3/DA): 2.70
REMARK 280
REMARK 280 CRYSTALLIZATION CONDITIONS: PH 7.4
REMARK 290
REMARK 290 CRYSTALLOGRAPHIC SYMMETRY
REMARK 290 SYMMETRY OPERATORS FOR SPACE GROUP: C 1 2 1
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+1/2,Y+1/2,Z
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 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 22.25300
REMARK 290 SMTRY2 3 0.000000 1.000000 0.000000 63.34400
REMARK 290 SMTRY3 3 0.000000 0.000000 1.000000 0.00000
REMARK 290 SMTRY1 4 -1.000000 0.000000 0.000000 22.25300
REMARK 290 SMTRY2 4 0.000000 1.000000 0.000000 63.34400
REMARK 290 SMTRY3 4 0.000000 0.000000 -1.000000 0.00000
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 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 350
REMARK 350 BIOMOLECULE: 2
REMARK 350 SOFTWARE DETERMINED QUATERNARY STRUCTURE: MONOMERIC
REMARK 350 SOFTWARE USED: PISA
REMARK 350 APPLY THE FOLLOWING TO CHAINS: 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 ALA A 835
REMARK 465 PHE A 836
REMARK 465 GLU A 837
REMARK 465 ASP A 838
REMARK 465 ARG A 839
REMARK 465 ASP A 840
REMARK 465 PRO A 841
REMARK 465 THR A 842
REMARK 465 GLN A 843
REMARK 465 LYS A 857
REMARK 465 GLY A 858
REMARK 465 ASN A 859
REMARK 465 PHE A 860
REMARK 465 SER A 919
REMARK 465 ALA A 920
REMARK 465 GLY A 921
REMARK 465 ARG A 922
REMARK 465 LYS A 1011
REMARK 465 GLU A 1012
REMARK 465 PRO A 1013
REMARK 465 GLY A 1014
REMARK 465 ALA A 1131
REMARK 465 GLY A 1132
REMARK 465 ALA B 835
REMARK 465 PHE B 836
REMARK 465 GLU B 837
REMARK 465 ASP B 838
REMARK 465 ARG B 839
REMARK 465 ASP B 840
REMARK 465 PRO B 841
REMARK 465 THR B 842
REMARK 465 GLN B 885
REMARK 465 HIS B 886
REMARK 465 SER B 887
REMARK 465 THR B 888
REMARK 465 GLU B 889
REMARK 465 GLU B 890
REMARK 465 TYR B 918
REMARK 465 SER B 919
REMARK 465 ALA B 920
REMARK 465 GLY B 921
REMARK 465 ARG B 922
REMARK 465 ARG B 923
REMARK 465 ASN B 924
REMARK 465 GLY B 1132
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 885 CG CD OE1 NE2
REMARK 470 HIS A 886 CG ND1 CD2 CE1 NE2
REMARK 470 GLU A 889 CG CD OE1 OE2
REMARK 470 GLU A 890 CG CD OE1 OE2
REMARK 470 ARG A 893 CG CD NE CZ NH1 NH2
REMARK 470 GLN A 906 CG CD OE1 NE2
REMARK 470 ARG A 923 CG CD NE CZ NH1 NH2
REMARK 470 GLN A1003 CG CD OE1 NE2
REMARK 470 LYS A1005 CG CD CE NZ
REMARK 470 LYS A1053 CD CE NZ
REMARK 470 GLN A1070 CG CD OE1 NE2
REMARK 470 LYS A1083 CG CD CE NZ
REMARK 470 GLN B 843 CG CD OE1 NE2
REMARK 470 LYS B 850 CG CD CE NZ
REMARK 470 LYS B 857 CD CE NZ
REMARK 470 PHE B 860 CG CD1 CD2 CE1 CE2 CZ
REMARK 470 GLN B 872 CG CD OE1 NE2
REMARK 470 LYS B1011 CG CD CE NZ
REMARK 470 GLU B1015 CG CD OE1 OE2
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 ARG B 1063 CB CG CD NE CZ NH1 NH2
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 975 -12.58 82.29
REMARK 500 ASN A1085 19.80 59.11
REMARK 500 TRP A1106 56.30 -97.61
REMARK 500 ASN B 859 -90.07 -86.24
REMARK 500 HIS B 944 32.35 -141.03
REMARK 500 ARG B 975 -4.77 67.31
REMARK 500 ASP B 976 32.34 -148.64
REMARK 500 LYS B1011 12.00 59.97
REMARK 500 TRP B1106 49.53 -99.34
REMARK 500
REMARK 500 REMARK: NULL
REMARK 500
REMARK 500 GEOMETRY AND STEREOCHEMISTRY
REMARK 500 SUBTOPIC: NON-CIS, NON-TRANS
REMARK 500
REMARK 500 THE FOLLOWING PEPTIDE BONDS DEVIATE SIGNIFICANTLY FROM BOTH
REMARK 500 CIS AND TRANS CONFORMATION. CIS BONDS, IF ANY, ARE LISTED
REMARK 500 ON CISPEP RECORDS. TRANS IS DEFINED AS 180 +/- 30 AND
REMARK 500 CIS IS DEFINED AS 0 +/- 30 DEGREES.
REMARK 500 MODEL OMEGA
REMARK 500 GLU B 1012 PRO B 1013 -149.52
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 F9J A 2133
REMARK 800
REMARK 800 SITE_IDENTIFIER: AC2
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: BINDING SITE FOR RESIDUE F9J B 2134
REMARK 800
REMARK 800 SITE_IDENTIFIER: AC3
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: BINDING SITE FOR RESIDUE ACE B 2135
REMARK 800
REMARK 800 SITE_IDENTIFIER: AC4
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: BINDING SITE FOR RESIDUE ACE A 2134
REMARK 800
REMARK 800 SITE_IDENTIFIER: AC5
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: BINDING SITE FOR RESIDUE ACE A 2135
DBREF 3ZMM A 835 1132 UNP O60674 JAK2_HUMAN 835 1132
DBREF 3ZMM B 835 1132 UNP O60674 JAK2_HUMAN 835 1132
SEQADV 3ZMM ALA A 943 UNP O60674 LYS 943 ENGINEERED MUTATION
SEQADV 3ZMM ALA A 945 UNP O60674 LYS 945 ENGINEERED MUTATION
SEQADV 3ZMM GLN A 1129 UNP O60674 ASN 1129 CONFLICT
SEQADV 3ZMM ALA B 943 UNP O60674 LYS 943 ENGINEERED MUTATION
SEQADV 3ZMM ALA B 945 UNP O60674 LYS 945 ENGINEERED MUTATION
SEQADV 3ZMM GLN B 1129 UNP O60674 ASN 1129 CONFLICT
SEQRES 1 A 298 ALA PHE GLU ASP ARG ASP PRO THR GLN PHE GLU GLU ARG
SEQRES 2 A 298 HIS LEU LYS PHE LEU GLN GLN LEU GLY LYS GLY ASN PHE
SEQRES 3 A 298 GLY SER VAL GLU MET CYS ARG TYR ASP PRO LEU GLN ASP
SEQRES 4 A 298 ASN THR GLY GLU VAL VAL ALA VAL LYS LYS LEU GLN HIS
SEQRES 5 A 298 SER THR GLU GLU HIS LEU ARG ASP PHE GLU ARG GLU ILE
SEQRES 6 A 298 GLU ILE LEU LYS SER LEU GLN HIS ASP ASN ILE VAL LYS
SEQRES 7 A 298 TYR LYS GLY VAL CYS TYR SER ALA GLY ARG ARG ASN LEU
SEQRES 8 A 298 LYS LEU ILE MET GLU TYR LEU PRO TYR GLY SER LEU ARG
SEQRES 9 A 298 ASP TYR LEU GLN ALA HIS ALA GLU ARG ILE ASP HIS ILE
SEQRES 10 A 298 LYS LEU LEU GLN TYR THR SER GLN ILE CYS LYS GLY MET
SEQRES 11 A 298 GLU TYR LEU GLY THR LYS ARG TYR ILE HIS ARG ASP LEU
SEQRES 12 A 298 ALA THR ARG ASN ILE LEU VAL GLU ASN GLU ASN ARG VAL
SEQRES 13 A 298 LYS ILE GLY ASP PHE GLY LEU THR LYS VAL LEU PRO GLN
SEQRES 14 A 298 ASP LYS GLU PTR PTR LYS VAL LYS GLU PRO GLY GLU SER
SEQRES 15 A 298 PRO ILE PHE TRP TYR ALA PRO GLU SER LEU THR GLU SER
SEQRES 16 A 298 LYS PHE SER VAL ALA SER ASP VAL TRP SER PHE GLY VAL
SEQRES 17 A 298 VAL LEU TYR GLU LEU PHE THR TYR ILE GLU LYS SER LYS
SEQRES 18 A 298 SER PRO PRO ALA GLU PHE MET ARG MET ILE GLY ASN ASP
SEQRES 19 A 298 LYS GLN GLY GLN MET ILE VAL PHE HIS LEU ILE GLU LEU
SEQRES 20 A 298 LEU LYS ASN ASN GLY ARG LEU PRO ARG PRO ASP GLY CYS
SEQRES 21 A 298 PRO ASP GLU ILE TYR MET ILE MET THR GLU CYS TRP ASN
SEQRES 22 A 298 ASN ASN VAL ASN GLN ARG PRO SER PHE ARG ASP LEU ALA
SEQRES 23 A 298 LEU ARG VAL ASP GLN ILE ARG ASP GLN MET ALA GLY
SEQRES 1 B 298 ALA PHE GLU ASP ARG ASP PRO THR GLN PHE GLU GLU ARG
SEQRES 2 B 298 HIS LEU LYS PHE LEU GLN GLN LEU GLY LYS GLY ASN PHE
SEQRES 3 B 298 GLY SER VAL GLU MET CYS ARG TYR ASP PRO LEU GLN ASP
SEQRES 4 B 298 ASN THR GLY GLU VAL VAL ALA VAL LYS LYS LEU GLN HIS
SEQRES 5 B 298 SER THR GLU GLU HIS LEU ARG ASP PHE GLU ARG GLU ILE
SEQRES 6 B 298 GLU ILE LEU LYS SER LEU GLN HIS ASP ASN ILE VAL LYS
SEQRES 7 B 298 TYR LYS GLY VAL CYS TYR SER ALA GLY ARG ARG ASN LEU
SEQRES 8 B 298 LYS LEU ILE MET GLU TYR LEU PRO TYR GLY SER LEU ARG
SEQRES 9 B 298 ASP TYR LEU GLN ALA HIS ALA GLU ARG ILE ASP HIS ILE
SEQRES 10 B 298 LYS LEU LEU GLN TYR THR SER GLN ILE CYS LYS GLY MET
SEQRES 11 B 298 GLU TYR LEU GLY THR LYS ARG TYR ILE HIS ARG ASP LEU
SEQRES 12 B 298 ALA THR ARG ASN ILE LEU VAL GLU ASN GLU ASN ARG VAL
SEQRES 13 B 298 LYS ILE GLY ASP PHE GLY LEU THR LYS VAL LEU PRO GLN
SEQRES 14 B 298 ASP LYS GLU PTR PTR LYS VAL LYS GLU PRO GLY GLU SER
SEQRES 15 B 298 PRO ILE PHE TRP TYR ALA PRO GLU SER LEU THR GLU SER
SEQRES 16 B 298 LYS PHE SER VAL ALA SER ASP VAL TRP SER PHE GLY VAL
SEQRES 17 B 298 VAL LEU TYR GLU LEU PHE THR TYR ILE GLU LYS SER LYS
SEQRES 18 B 298 SER PRO PRO ALA GLU PHE MET ARG MET ILE GLY ASN ASP
SEQRES 19 B 298 LYS GLN GLY GLN MET ILE VAL PHE HIS LEU ILE GLU LEU
SEQRES 20 B 298 LEU LYS ASN ASN GLY ARG LEU PRO ARG PRO ASP GLY CYS
SEQRES 21 B 298 PRO ASP GLU ILE TYR MET ILE MET THR GLU CYS TRP ASN
SEQRES 22 B 298 ASN ASN VAL ASN GLN ARG PRO SER PHE ARG ASP LEU ALA
SEQRES 23 B 298 LEU ARG VAL ASP GLN ILE ARG ASP GLN MET ALA GLY
MODRES 3ZMM PTR A 1007 TYR O-PHOSPHOTYROSINE
MODRES 3ZMM PTR A 1008 TYR O-PHOSPHOTYROSINE
MODRES 3ZMM PTR B 1007 TYR O-PHOSPHOTYROSINE
MODRES 3ZMM PTR B 1008 TYR O-PHOSPHOTYROSINE
HET PTR A1007 16
HET PTR A1008 16
HET PTR B1007 16
HET PTR B1008 16
HET F9J A2133 30
HET ACE A2134 3
HET ACE A2135 3
HET F9J B2134 30
HET ACE B2135 3
HETNAM PTR O-PHOSPHOTYROSINE
HETNAM F9J 5-FLUORO-4-[(1S)-1-(5-FLUOROPYRIMIDIN-2-YL)ETHOXY]-N-
HETNAM 2 F9J (5-METHYL-1H-PYRAZOL-3-YL)-6-MORPHOLINO-PYRIMIDIN-2-
HETNAM 3 F9J AMINE
HETNAM ACE ACETYL GROUP
HETSYN PTR PHOSPHONOTYROSINE
FORMUL 1 PTR 4(C9 H12 N O6 P)
FORMUL 3 F9J 2(C18 H20 F2 N8 O2)
FORMUL 4 ACE 3(C2 H4 O)
FORMUL 8 HOH *140(H2 O)
HELIX 1 1 THR A 888 SER A 904 1 17
HELIX 2 2 SER A 936 ALA A 945 1 10
HELIX 3 3 GLU A 946 ILE A 948 5 3
HELIX 4 4 ASP A 949 LYS A 970 1 22
HELIX 5 5 ALA A 978 ARG A 980 5 3
HELIX 6 6 PRO A 1017 TYR A 1021 5 5
HELIX 7 7 ALA A 1022 SER A 1029 1 8
HELIX 8 8 SER A 1032 THR A 1049 1 18
HELIX 9 9 GLU A 1052 LYS A 1055 5 4
HELIX 10 10 SER A 1056 GLY A 1066 1 11
HELIX 11 11 GLN A 1070 GLN A 1072 5 3
HELIX 12 12 MET A 1073 ASN A 1084 1 12
HELIX 13 13 PRO A 1095 TRP A 1106 1 12
HELIX 14 14 ASN A 1109 ARG A 1113 5 5
HELIX 15 15 SER A 1115 ASP A 1128 1 14
HELIX 16 16 GLU B 845 ARG B 847 5 3
HELIX 17 17 HIS B 891 SER B 904 1 14
HELIX 18 18 SER B 936 ALA B 945 1 10
HELIX 19 19 GLU B 946 ILE B 948 5 3
HELIX 20 20 ASP B 949 LYS B 970 1 22
HELIX 21 21 ALA B 978 ARG B 980 5 3
HELIX 22 22 PRO B 1017 TYR B 1021 5 5
HELIX 23 23 ALA B 1022 SER B 1029 1 8
HELIX 24 24 SER B 1032 THR B 1049 1 18
HELIX 25 25 GLU B 1052 LYS B 1055 5 4
HELIX 26 26 SER B 1056 GLY B 1066 1 11
HELIX 27 27 GLY B 1071 ASN B 1084 1 14
HELIX 28 28 PRO B 1095 TRP B 1106 1 12
HELIX 29 29 ASN B 1109 ARG B 1113 5 5
HELIX 30 30 SER B 1115 MET B 1130 1 16
SHEET 1 AA 5 LEU A 849 GLY A 856 0
SHEET 2 AA 5 SER A 862 TYR A 868 -1 O VAL A 863 N LEU A 855
SHEET 3 AA 5 VAL A 878 LYS A 883 -1 O VAL A 879 N CYS A 866
SHEET 4 AA 5 LYS A 926 GLU A 930 -1 O LEU A 927 N LYS A 882
SHEET 5 AA 5 TYR A 913 CYS A 917 -1 N LYS A 914 O ILE A 928
SHEET 1 AB 2 TYR A 972 ILE A 973 0
SHEET 2 AB 2 LYS A 999 VAL A1000 -1 O LYS A 999 N ILE A 973
SHEET 1 AC 2 ILE A 982 ASN A 986 0
SHEET 2 AC 2 ARG A 989 ILE A 992 -1 O ARG A 989 N GLU A 985
SHEET 1 AD 2 PTR A1008 LYS A1009 0
SHEET 2 AD 2 LYS A1030 PHE A1031 -1 O PHE A1031 N PTR A1008
SHEET 1 BA 5 LEU B 849 GLY B 856 0
SHEET 2 BA 5 SER B 862 TYR B 868 -1 O VAL B 863 N GLY B 856
SHEET 3 BA 5 VAL B 878 LYS B 883 -1 O VAL B 879 N CYS B 866
SHEET 4 BA 5 LEU B 927 GLU B 930 -1 O LEU B 927 N LYS B 882
SHEET 5 BA 5 TYR B 913 VAL B 916 -1 N LYS B 914 O ILE B 928
SHEET 1 BB 2 TYR B 972 ILE B 973 0
SHEET 2 BB 2 LYS B 999 VAL B1000 -1 O LYS B 999 N ILE B 973
SHEET 1 BC 2 ILE B 982 ASN B 986 0
SHEET 2 BC 2 ARG B 989 ILE B 992 -1 O ARG B 989 N GLU B 985
SHEET 1 BD 2 PTR B1008 LYS B1009 0
SHEET 2 BD 2 LYS B1030 PHE B1031 -1 O PHE B1031 N PTR B1008
LINK C GLU A1006 N PTR A1007 1555 1555 1.33
LINK C PTR A1007 N PTR A1008 1555 1555 1.33
LINK C PTR A1008 N LYS A1009 1555 1555 1.33
LINK C GLU B1006 N PTR B1007 1555 1555 1.33
LINK C PTR B1007 N PTR B1008 1555 1555 1.33
LINK C PTR B1008 N LYS B1009 1555 1555 1.33
SITE 1 AC1 12 LEU A 855 ALA A 880 MET A 929 GLU A 930
SITE 2 AC1 12 TYR A 931 LEU A 932 GLY A 935 ARG A 980
SITE 3 AC1 12 ASN A 981 LEU A 983 GLY A 993 HOH A2004
SITE 1 AC2 11 LEU B 855 ALA B 880 MET B 929 GLU B 930
SITE 2 AC2 11 TYR B 931 LEU B 932 GLY B 935 ARG B 980
SITE 3 AC2 11 ASN B 981 LEU B 983 GLY B 993
SITE 1 AC3 5 TYR A 931 PRO A 933 ARG B1090 ASP B1092
SITE 2 AC3 5 GLY B1093
SITE 1 AC4 3 GLU A 864 LYS A 926 ACE A2135
SITE 1 AC5 2 PHE A 851 ACE A2134
CRYST1 44.506 126.688 135.593 90.00 97.22 90.00 C 1 2 1 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 0.022469 0.000000 0.002846 0.00000
SCALE2 0.000000 0.007893 0.000000 0.00000
SCALE3 0.000000 0.000000 0.007434 0.00000
(ATOM LINES ARE NOT SHOWN.)
END
