HEADER TRANSFERASE/TRANSFERASE INHIBITOR 06-NOV-12 4HVD
TITLE JAK3 KINASE DOMAIN IN COMPLEX WITH 2-CYCLOPROPYL-5H-PYRROLO[2,3-
TITLE 2 B]PYRAZINE-7-CARBOXYLIC ACID ((S)-1,2,2-TRIMETHYL-PROPYL)-AMIDE
COMPND MOL_ID: 1;
COMPND 2 MOLECULE: TYROSINE-PROTEIN KINASE JAK3;
COMPND 3 CHAIN: A;
COMPND 4 FRAGMENT: RESIDUES 811-1124;
COMPND 5 SYNONYM: JANUS KINASE 3, JAK-3, LEUKOCYTE JANUS KINASE, L-JAK;
COMPND 6 EC: 2.7.10.2;
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 GENE: JAK3;
SOURCE 6 EXPRESSION_SYSTEM: SPODOPTERA FRUGIPERDA;
SOURCE 7 EXPRESSION_SYSTEM_TAXID: 7108
KEYWDS KINASE-INHIBITOR COMPLEX, TRANSFERASE-TRANSFERASE INHIBITOR COMPLEX
EXPDTA X-RAY DIFFRACTION
AUTHOR A.KUGLSTATTER,A.SHAO
REVDAT 3 20-SEP-23 4HVD 1 REMARK SEQADV
REVDAT 2 30-JAN-13 4HVD 1 JRNL
REVDAT 1 16-JAN-13 4HVD 0
JRNL AUTH M.SOTH,J.C.HERMANN,C.YEE,M.ALAM,J.W.BARNETT,P.BERRY,
JRNL AUTH 2 M.F.BROWNER,K.FRANK,S.FRAUCHIGER,S.HARRIS,Y.HE,
JRNL AUTH 3 M.HEKMAT-NEJAD,T.HENDRICKS,R.HENNINGSEN,R.HILGENKAMP,H.HO,
JRNL AUTH 4 A.HOFFMAN,P.Y.HSU,D.Q.HU,A.ITANO,S.JAIME-FIGUEROA,
JRNL AUTH 5 A.JAHANGIR,S.JIN,A.KUGLSTATTER,A.K.KUTACH,C.LIAO,S.LYNCH,
JRNL AUTH 6 J.MENKE,L.NIU,V.PATEL,A.RAILKAR,D.ROY,A.SHAO,D.SHAW,
JRNL AUTH 7 S.STEINER,Y.SUN,S.L.TAN,S.WANG,M.D.VU
JRNL TITL 3-AMIDO PYRROLOPYRAZINE JAK KINASE INHIBITORS: DEVELOPMENT
JRNL TITL 2 OF A JAK3 VS JAK1 SELECTIVE INHIBITOR AND EVALUATION IN
JRNL TITL 3 CELLULAR AND IN VIVO MODELS.
JRNL REF J.MED.CHEM. V. 56 345 2013
JRNL REFN ISSN 0022-2623
JRNL PMID 23214979
JRNL DOI 10.1021/JM301646K
REMARK 2
REMARK 2 RESOLUTION. 1.85 ANGSTROMS.
REMARK 3
REMARK 3 REFINEMENT.
REMARK 3 PROGRAM : REFMAC 5.2.0019
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) : 1.85
REMARK 3 RESOLUTION RANGE LOW (ANGSTROMS) : 34.74
REMARK 3 DATA CUTOFF (SIGMA(F)) : NULL
REMARK 3 COMPLETENESS FOR RANGE (%) : 82.7
REMARK 3 NUMBER OF REFLECTIONS : 21755
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) : 0.225
REMARK 3 R VALUE (WORKING SET) : 0.223
REMARK 3 FREE R VALUE : 0.259
REMARK 3 FREE R VALUE TEST SET SIZE (%) : 5.100
REMARK 3 FREE R VALUE TEST SET COUNT : 1167
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) : 1.85
REMARK 3 BIN RESOLUTION RANGE LOW (A) : 1.90
REMARK 3 REFLECTION IN BIN (WORKING SET) : 323
REMARK 3 BIN COMPLETENESS (WORKING+TEST) (%) : 17.04
REMARK 3 BIN R VALUE (WORKING SET) : 0.2970
REMARK 3 BIN FREE R VALUE SET COUNT : 16
REMARK 3 BIN FREE R VALUE : 0.2770
REMARK 3
REMARK 3 NUMBER OF NON-HYDROGEN ATOMS USED IN REFINEMENT.
REMARK 3 PROTEIN ATOMS : 2215
REMARK 3 NUCLEIC ACID ATOMS : 0
REMARK 3 HETEROGEN ATOMS : 31
REMARK 3 SOLVENT ATOMS : 131
REMARK 3
REMARK 3 B VALUES.
REMARK 3 FROM WILSON PLOT (A**2) : 26.60
REMARK 3 MEAN B VALUE (OVERALL, A**2) : 35.01
REMARK 3 OVERALL ANISOTROPIC B VALUE.
REMARK 3 B11 (A**2) : 1.46000
REMARK 3 B22 (A**2) : -0.25000
REMARK 3 B33 (A**2) : -1.21000
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): 0.197
REMARK 3 ESU BASED ON FREE R VALUE (A): 0.172
REMARK 3 ESU BASED ON MAXIMUM LIKELIHOOD (A): 0.130
REMARK 3 ESU FOR B VALUES BASED ON MAXIMUM LIKELIHOOD (A**2): 10.022
REMARK 3
REMARK 3 CORRELATION COEFFICIENTS.
REMARK 3 CORRELATION COEFFICIENT FO-FC : 0.944
REMARK 3 CORRELATION COEFFICIENT FO-FC FREE : 0.926
REMARK 3
REMARK 3 RMS DEVIATIONS FROM IDEAL VALUES COUNT RMS WEIGHT
REMARK 3 BOND LENGTHS REFINED ATOMS (A): 2304 ; 0.007 ; 0.022
REMARK 3 BOND LENGTHS OTHERS (A): NULL ; NULL ; NULL
REMARK 3 BOND ANGLES REFINED ATOMS (DEGREES): 3119 ; 0.976 ; 1.997
REMARK 3 BOND ANGLES OTHERS (DEGREES): NULL ; NULL ; NULL
REMARK 3 TORSION ANGLES, PERIOD 1 (DEGREES): 273 ; 4.751 ; 5.000
REMARK 3 TORSION ANGLES, PERIOD 2 (DEGREES): 107 ;33.894 ;22.804
REMARK 3 TORSION ANGLES, PERIOD 3 (DEGREES): 392 ;14.544 ;15.000
REMARK 3 TORSION ANGLES, PERIOD 4 (DEGREES): 21 ;16.650 ;15.000
REMARK 3 CHIRAL-CENTER RESTRAINTS (A**3): 330 ; 0.067 ; 0.200
REMARK 3 GENERAL PLANES REFINED ATOMS (A): 1777 ; 0.003 ; 0.020
REMARK 3 GENERAL PLANES OTHERS (A): NULL ; NULL ; NULL
REMARK 3 NON-BONDED CONTACTS REFINED ATOMS (A): 992 ; 0.178 ; 0.200
REMARK 3 NON-BONDED CONTACTS OTHERS (A): NULL ; NULL ; NULL
REMARK 3 NON-BONDED TORSION REFINED ATOMS (A): 1563 ; 0.304 ; 0.200
REMARK 3 NON-BONDED TORSION OTHERS (A): NULL ; NULL ; NULL
REMARK 3 H-BOND (X...Y) REFINED ATOMS (A): 147 ; 0.123 ; 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): 32 ; 0.152 ; 0.200
REMARK 3 SYMMETRY VDW OTHERS (A): NULL ; NULL ; NULL
REMARK 3 SYMMETRY H-BOND REFINED ATOMS (A): 8 ; 0.112 ; 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): 1429 ; 0.561 ; 1.500
REMARK 3 MAIN-CHAIN BOND OTHER ATOMS (A**2): NULL ; NULL ; NULL
REMARK 3 MAIN-CHAIN ANGLE REFINED ATOMS (A**2): 2219 ; 0.992 ; 2.000
REMARK 3 MAIN-CHAIN ANGLE OTHER ATOMS (A**2): NULL ; NULL ; NULL
REMARK 3 SIDE-CHAIN BOND REFINED ATOMS (A**2): 1007 ; 1.230 ; 3.000
REMARK 3 SIDE-CHAIN BOND OTHER ATOMS (A**2): NULL ; NULL ; NULL
REMARK 3 SIDE-CHAIN ANGLE REFINED ATOMS (A**2): 897 ; 2.028 ; 4.500
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 : 1
REMARK 3
REMARK 3 TLS GROUP : 1
REMARK 3 NUMBER OF COMPONENTS GROUP : 3
REMARK 3 COMPONENTS C SSSEQI TO C SSSEQI
REMARK 3 RESIDUE RANGE : A 1301 A 1431
REMARK 3 RESIDUE RANGE : A 1201 A 1202
REMARK 3 RESIDUE RANGE : A 815 A 1101
REMARK 3 ORIGIN FOR THE GROUP (A): 3.2617 -13.6160 -14.7465
REMARK 3 T TENSOR
REMARK 3 T11: -0.0173 T22: -0.0388
REMARK 3 T33: -0.0048 T12: 0.0155
REMARK 3 T13: 0.0074 T23: 0.0220
REMARK 3 L TENSOR
REMARK 3 L11: 0.3565 L22: 0.3347
REMARK 3 L33: 0.9277 L12: -0.0566
REMARK 3 L13: -0.1474 L23: 0.3679
REMARK 3 S TENSOR
REMARK 3 S11: 0.0337 S12: 0.0154 S13: 0.0353
REMARK 3 S21: -0.0598 S22: -0.0307 S23: -0.0137
REMARK 3 S31: 0.0008 S32: 0.0178 S33: -0.0030
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: NULL
REMARK 4
REMARK 4 4HVD COMPLIES WITH FORMAT V. 3.30, 13-JUL-11
REMARK 100
REMARK 100 THIS ENTRY HAS BEEN PROCESSED BY RCSB ON 12-NOV-12.
REMARK 100 THE DEPOSITION ID IS D_1000075967.
REMARK 200
REMARK 200 EXPERIMENTAL DETAILS
REMARK 200 EXPERIMENT TYPE : X-RAY DIFFRACTION
REMARK 200 DATE OF DATA COLLECTION : NULL
REMARK 200 TEMPERATURE (KELVIN) : 100
REMARK 200 PH : 6.0
REMARK 200 NUMBER OF CRYSTALS USED : 1
REMARK 200
REMARK 200 SYNCHROTRON (Y/N) : Y
REMARK 200 RADIATION SOURCE : SSRL
REMARK 200 BEAMLINE : BL9-2
REMARK 200 X-RAY GENERATOR MODEL : NULL
REMARK 200 MONOCHROMATIC OR LAUE (M/L) : M
REMARK 200 WAVELENGTH OR RANGE (A) : 0.97929
REMARK 200 MONOCHROMATOR : NULL
REMARK 200 OPTICS : NULL
REMARK 200
REMARK 200 DETECTOR TYPE : CCD
REMARK 200 DETECTOR MANUFACTURER : ADSC QUANTUM 315R
REMARK 200 INTENSITY-INTEGRATION SOFTWARE : HKL-2000
REMARK 200 DATA SCALING SOFTWARE : HKL-2000
REMARK 200
REMARK 200 NUMBER OF UNIQUE REFLECTIONS : 21755
REMARK 200 RESOLUTION RANGE HIGH (A) : 1.850
REMARK 200 RESOLUTION RANGE LOW (A) : 44.680
REMARK 200 REJECTION CRITERIA (SIGMA(I)) : NULL
REMARK 200
REMARK 200 OVERALL.
REMARK 200 COMPLETENESS FOR RANGE (%) : 82.7
REMARK 200 DATA REDUNDANCY : 4.700
REMARK 200 R MERGE (I) : NULL
REMARK 200 R SYM (I) : 0.05000
REMARK 200 <I/SIGMA(I)> FOR THE DATA SET : 26.9000
REMARK 200
REMARK 200 IN THE HIGHEST RESOLUTION SHELL.
REMARK 200 HIGHEST RESOLUTION SHELL, RANGE HIGH (A) : 1.85
REMARK 200 HIGHEST RESOLUTION SHELL, RANGE LOW (A) : 1.90
REMARK 200 COMPLETENESS FOR SHELL (%) : 17.0
REMARK 200 DATA REDUNDANCY IN SHELL : 1.50
REMARK 200 R MERGE FOR SHELL (I) : NULL
REMARK 200 R SYM FOR SHELL (I) : 0.26300
REMARK 200 <I/SIGMA(I)> FOR SHELL : 2.300
REMARK 200
REMARK 200 DIFFRACTION PROTOCOL: SINGLE WAVELENGTH
REMARK 200 METHOD USED TO DETERMINE THE STRUCTURE: FOURIER SYNTHESIS
REMARK 200 SOFTWARE USED: PHASER
REMARK 200 STARTING MODEL: PDB ENTRY 1YVJ
REMARK 200
REMARK 200 REMARK: NULL
REMARK 280
REMARK 280 CRYSTAL
REMARK 280 SOLVENT CONTENT, VS (%): 44.48
REMARK 280 MATTHEWS COEFFICIENT, VM (ANGSTROMS**3/DA): 2.22
REMARK 280
REMARK 280 CRYSTALLIZATION CONDITIONS: 30% PEG3350, 0.1M MES, 0.2M MGCL, PH
REMARK 280 6.0, 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 23.40800
REMARK 290 SMTRY2 2 0.000000 -1.000000 0.000000 0.00000
REMARK 290 SMTRY3 2 0.000000 0.000000 1.000000 44.69600
REMARK 290 SMTRY1 3 -1.000000 0.000000 0.000000 0.00000
REMARK 290 SMTRY2 3 0.000000 1.000000 0.000000 37.70800
REMARK 290 SMTRY3 3 0.000000 0.000000 -1.000000 44.69600
REMARK 290 SMTRY1 4 1.000000 0.000000 0.000000 23.40800
REMARK 290 SMTRY2 4 0.000000 -1.000000 0.000000 37.70800
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 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 CYS A 811
REMARK 465 GLN A 812
REMARK 465 ASP A 813
REMARK 465 PRO A 814
REMARK 465 GLY A 892
REMARK 465 PRO A 893
REMARK 465 GLY A 894
REMARK 465 ARG A 895
REMARK 465 GLN A 896
REMARK 465 SER A 897
REMARK 465 GLY A 1039
REMARK 465 SER A 1040
REMARK 465 GLU A 1041
REMARK 465 ARG A 1042
REMARK 465 ASP A 1043
REMARK 465 SER A 1102
REMARK 465 ARG A 1103
REMARK 465 GLY A 1104
REMARK 465 CYS A 1105
REMARK 465 GLU A 1106
REMARK 465 THR A 1107
REMARK 465 HIS A 1108
REMARK 465 ALA A 1109
REMARK 465 PHE A 1110
REMARK 465 THR A 1111
REMARK 465 ALA A 1112
REMARK 465 HIS A 1113
REMARK 465 PRO A 1114
REMARK 465 GLU A 1115
REMARK 465 GLY A 1116
REMARK 465 LYS A 1117
REMARK 465 HIS A 1118
REMARK 465 HIS A 1119
REMARK 465 SER A 1120
REMARK 465 LEU A 1121
REMARK 465 SER A 1122
REMARK 465 PHE A 1123
REMARK 465 SER A 1124
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 ASN A 832 -106.53 63.31
REMARK 500 ARG A 948 -13.80 83.01
REMARK 500 ASP A 949 40.00 -141.37
REMARK 500 ALA A 966 -166.42 -128.55
REMARK 500 ASP A 967 76.56 58.39
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 PHU A 1201
REMARK 800
REMARK 800 SITE_IDENTIFIER: AC2
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: BINDING SITE FOR RESIDUE 933 A 1202
REMARK 900
REMARK 900 RELATED ENTRIES
REMARK 900 RELATED ID: 4HVG RELATED DB: PDB
REMARK 900 RELATED ID: 4HVH RELATED DB: PDB
REMARK 900 RELATED ID: 4HVI RELATED DB: PDB
DBREF 4HVD A 811 1124 UNP P52333 JAK3_HUMAN 811 1124
SEQADV 4HVD SER A 1040 UNP P52333 CYS 1040 ENGINEERED MUTATION
SEQADV 4HVD SER A 1048 UNP P52333 CYS 1048 ENGINEERED MUTATION
SEQRES 1 A 314 CYS GLN ASP PRO THR ILE PHE GLU GLU ARG HIS LEU LYS
SEQRES 2 A 314 TYR ILE SER GLN LEU GLY LYS GLY ASN PHE GLY SER VAL
SEQRES 3 A 314 GLU LEU CYS ARG TYR ASP PRO LEU GLY ASP ASN THR GLY
SEQRES 4 A 314 ALA LEU VAL ALA VAL LYS GLN LEU GLN HIS SER GLY PRO
SEQRES 5 A 314 ASP GLN GLN ARG ASP PHE GLN ARG GLU ILE GLN ILE LEU
SEQRES 6 A 314 LYS ALA LEU HIS SER ASP PHE ILE VAL LYS TYR ARG GLY
SEQRES 7 A 314 VAL SER TYR GLY PRO GLY ARG GLN SER LEU ARG LEU VAL
SEQRES 8 A 314 MET GLU TYR LEU PRO SER GLY CYS LEU ARG ASP PHE LEU
SEQRES 9 A 314 GLN ARG HIS ARG ALA ARG LEU ASP ALA SER ARG LEU LEU
SEQRES 10 A 314 LEU TYR SER SER GLN ILE CYS LYS GLY MET GLU TYR LEU
SEQRES 11 A 314 GLY SER ARG ARG CYS VAL HIS ARG ASP LEU ALA ALA ARG
SEQRES 12 A 314 ASN ILE LEU VAL GLU SER GLU ALA HIS VAL LYS ILE ALA
SEQRES 13 A 314 ASP PHE GLY LEU ALA LYS LEU LEU PRO LEU ASP LYS ASP
SEQRES 14 A 314 TYR TYR VAL VAL ARG GLU PRO GLY GLN SER PRO ILE PHE
SEQRES 15 A 314 TRP TYR ALA PRO GLU SER LEU SER ASP ASN ILE PHE SER
SEQRES 16 A 314 ARG GLN SER ASP VAL TRP SER PHE GLY VAL VAL LEU TYR
SEQRES 17 A 314 GLU LEU PHE THR TYR CYS ASP LYS SER CYS SER PRO SER
SEQRES 18 A 314 ALA GLU PHE LEU ARG MET MET GLY SER GLU ARG ASP VAL
SEQRES 19 A 314 PRO ALA LEU SER ARG LEU LEU GLU LEU LEU GLU GLU GLY
SEQRES 20 A 314 GLN ARG LEU PRO ALA PRO PRO ALA CYS PRO ALA GLU VAL
SEQRES 21 A 314 HIS GLU LEU MET LYS LEU CYS TRP ALA PRO SER PRO GLN
SEQRES 22 A 314 ASP ARG PRO SER PHE SER ALA LEU GLY PRO GLN LEU ASP
SEQRES 23 A 314 MET LEU TRP SER GLY SER ARG GLY CYS GLU THR HIS ALA
SEQRES 24 A 314 PHE THR ALA HIS PRO GLU GLY LYS HIS HIS SER LEU SER
SEQRES 25 A 314 PHE SER
HET PHU A1201 10
HET 933 A1202 21
HETNAM PHU 1-PHENYLUREA
HETNAM 933 2-CYCLOPROPYL-N-[(2S)-3,3-DIMETHYLBUTAN-2-YL]-5H-
HETNAM 2 933 PYRROLO[2,3-B]PYRAZINE-7-CARBOXAMIDE
HETSYN PHU PHENYLUREA
FORMUL 2 PHU C7 H8 N2 O
FORMUL 3 933 C16 H22 N4 O
FORMUL 4 HOH *131(H2 O)
HELIX 1 1 GLU A 818 ARG A 820 5 3
HELIX 2 2 GLY A 861 ALA A 877 1 17
HELIX 3 3 CYS A 909 ARG A 918 1 10
HELIX 4 4 ALA A 919 LEU A 921 5 3
HELIX 5 5 ASP A 922 ARG A 943 1 22
HELIX 6 6 ALA A 951 ARG A 953 5 3
HELIX 7 7 PRO A 990 TYR A 994 5 5
HELIX 8 8 ALA A 995 ASN A 1002 1 8
HELIX 9 9 ARG A 1006 THR A 1022 1 17
HELIX 10 10 ASP A 1025 CYS A 1028 5 4
HELIX 11 11 SER A 1029 MET A 1038 1 10
HELIX 12 12 PRO A 1045 GLU A 1056 1 12
HELIX 13 13 PRO A 1067 TRP A 1078 1 12
HELIX 14 14 SER A 1081 ARG A 1085 5 5
HELIX 15 15 SER A 1087 GLY A 1101 1 15
SHEET 1 A 5 LEU A 822 GLY A 831 0
SHEET 2 A 5 GLY A 834 TYR A 841 -1 O VAL A 836 N LEU A 828
SHEET 3 A 5 ALA A 850 LEU A 857 -1 O VAL A 854 N GLU A 837
SHEET 4 A 5 ARG A 899 GLU A 903 -1 O LEU A 900 N LYS A 855
SHEET 5 A 5 TYR A 886 SER A 890 -1 N ARG A 887 O VAL A 901
SHEET 1 B 2 CYS A 945 VAL A 946 0
SHEET 2 B 2 LYS A 972 LEU A 973 -1 O LYS A 972 N VAL A 946
SHEET 1 C 2 ILE A 955 SER A 959 0
SHEET 2 C 2 HIS A 962 ILE A 965 -1 O LYS A 964 N LEU A 956
SHEET 1 D 2 TYR A 980 VAL A 982 0
SHEET 2 D 2 ILE A1003 SER A1005 -1 O PHE A1004 N TYR A 981
SITE 1 AC1 6 TRP A1011 PRO A1030 ARG A1059 LEU A1060
SITE 2 AC1 6 TRP A1078 HOH A1338
SITE 1 AC2 9 LEU A 828 GLY A 829 ALA A 853 GLU A 903
SITE 2 AC2 9 TYR A 904 LEU A 905 ASN A 954 LEU A 956
SITE 3 AC2 9 HOH A1316
CRYST1 46.816 75.416 89.392 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 0.021360 0.000000 0.000000 0.00000
SCALE2 0.000000 0.013260 0.000000 0.00000
SCALE3 0.000000 0.000000 0.011187 0.00000
(ATOM LINES ARE NOT SHOWN.)
END
