HEADER TRANSFERASE/TRANSFERASE INHIBITOR 10-JUL-17 5WEV
TITLE IDENTIFICATION OF AN IMIDAZOPYRIDINE SCAFFOLD TO GENERATE POTENT AND
TITLE 2 SELECTIVE TYK2 INHIBITORS THAT DEMONSTRATE ACTIVITY IN AN IN VIVO
TITLE 3 PSORIASIS MODEL
COMPND MOL_ID: 1;
COMPND 2 MOLECULE: TYROSINE-PROTEIN KINASE JAK2;
COMPND 3 CHAIN: A;
COMPND 4 FRAGMENT: UNP RESIDUES 833-1132;
COMPND 5 SYNONYM: JANUS KINASE 2,JAK-2;
COMPND 6 EC: 2.7.10.2;
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: JAK2;
SOURCE 6 EXPRESSION_SYSTEM: UNIDENTIFIED BACULOVIRUS;
SOURCE 7 EXPRESSION_SYSTEM_TAXID: 10469
KEYWDS JAK2, KINASE, INHIBITOR, TRANSFERASE-TRANSFERASE INHIBITOR COMPLEX
EXPDTA X-RAY DIFFRACTION
AUTHOR M.H.ULTSCH,S.MAGNUSON
REVDAT 4 15-NOV-23 5WEV 1 REMARK
REVDAT 3 04-OCT-23 5WEV 1 REMARK
REVDAT 2 20-SEP-17 5WEV 1 JRNL
REVDAT 1 06-SEP-17 5WEV 0
JRNL AUTH J.LIANG,A.VAN ABBEMA,M.BALAZS,K.BARRETT,L.BEREZHKOVSKY,
JRNL AUTH 2 W.S.BLAIR,C.CHANG,D.DELAROSA,J.DEVOSS,J.DRISCOLL,
JRNL AUTH 3 C.EIGENBROT,S.GOODACRE,N.GHILARDI,C.MACLEOD,A.JOHNSON,
JRNL AUTH 4 P.BIR KOHLI,Y.LAI,Z.LIN,P.MANTIK,K.MENGHRAJANI,H.NGUYEN,
JRNL AUTH 5 I.PENG,A.SAMBRONE,S.SHIA,J.SMITH,S.SOHN,V.TSUI,M.ULTSCH,
JRNL AUTH 6 K.WILLIAMS,L.C.WU,W.YANG,B.ZHANG,S.MAGNUSON
JRNL TITL IDENTIFICATION OF AN IMIDAZOPYRIDINE SCAFFOLD TO GENERATE
JRNL TITL 2 POTENT AND SELECTIVE TYK2 INHIBITORS THAT DEMONSTRATE
JRNL TITL 3 ACTIVITY IN AN IN VIVO PSORIASIS MODEL.
JRNL REF BIOORG. MED. CHEM. LETT. V. 27 4370 2017
JRNL REFN ESSN 1464-3405
JRNL PMID 28830649
JRNL DOI 10.1016/J.BMCL.2017.08.022
REMARK 2
REMARK 2 RESOLUTION. 1.85 ANGSTROMS.
REMARK 3
REMARK 3 REFINEMENT.
REMARK 3 PROGRAM : REFMAC 5.8.0155
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) : 1.85
REMARK 3 RESOLUTION RANGE LOW (ANGSTROMS) : 40.00
REMARK 3 DATA CUTOFF (SIGMA(F)) : NULL
REMARK 3 COMPLETENESS FOR RANGE (%) : 99.2
REMARK 3 NUMBER OF REFLECTIONS : 29409
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) : 0.167
REMARK 3 R VALUE (WORKING SET) : 0.166
REMARK 3 FREE R VALUE : 0.194
REMARK 3 FREE R VALUE TEST SET SIZE (%) : 5.700
REMARK 3 FREE R VALUE TEST SET COUNT : 1768
REMARK 3
REMARK 3 FIT IN THE HIGHEST RESOLUTION BIN.
REMARK 3 TOTAL NUMBER OF BINS USED : 10
REMARK 3 BIN RESOLUTION RANGE HIGH (A) : 1.85
REMARK 3 BIN RESOLUTION RANGE LOW (A) : 1.95
REMARK 3 REFLECTION IN BIN (WORKING SET) : 4187
REMARK 3 BIN COMPLETENESS (WORKING+TEST) (%) : 96.50
REMARK 3 BIN R VALUE (WORKING SET) : 0.2030
REMARK 3 BIN FREE R VALUE SET COUNT : 224
REMARK 3 BIN FREE R VALUE : 0.2630
REMARK 3
REMARK 3 NUMBER OF NON-HYDROGEN ATOMS USED IN REFINEMENT.
REMARK 3 PROTEIN ATOMS : 2447
REMARK 3 NUCLEIC ACID ATOMS : 0
REMARK 3 HETEROGEN ATOMS : 23
REMARK 3 SOLVENT ATOMS : 139
REMARK 3
REMARK 3 B VALUES.
REMARK 3 FROM WILSON PLOT (A**2) : NULL
REMARK 3 MEAN B VALUE (OVERALL, A**2) : 27.97
REMARK 3 OVERALL ANISOTROPIC B VALUE.
REMARK 3 B11 (A**2) : 1.07000
REMARK 3 B22 (A**2) : -0.58000
REMARK 3 B33 (A**2) : -0.64000
REMARK 3 B12 (A**2) : 0.00000
REMARK 3 B13 (A**2) : 0.62000
REMARK 3 B23 (A**2) : 0.00000
REMARK 3
REMARK 3 ESTIMATED OVERALL COORDINATE ERROR.
REMARK 3 ESU BASED ON R VALUE (A): 0.117
REMARK 3 ESU BASED ON FREE R VALUE (A): 0.110
REMARK 3 ESU BASED ON MAXIMUM LIKELIHOOD (A): 0.075
REMARK 3 ESU FOR B VALUES BASED ON MAXIMUM LIKELIHOOD (A**2): 2.504
REMARK 3
REMARK 3 CORRELATION COEFFICIENTS.
REMARK 3 CORRELATION COEFFICIENT FO-FC : 0.964
REMARK 3 CORRELATION COEFFICIENT FO-FC FREE : 0.958
REMARK 3
REMARK 3 RMS DEVIATIONS FROM IDEAL VALUES COUNT RMS WEIGHT
REMARK 3 BOND LENGTHS REFINED ATOMS (A): 2542 ; 0.009 ; 0.019
REMARK 3 BOND LENGTHS OTHERS (A): NULL ; NULL ; NULL
REMARK 3 BOND ANGLES REFINED ATOMS (DEGREES): 3432 ; 1.424 ; 1.993
REMARK 3 BOND ANGLES OTHERS (DEGREES): NULL ; NULL ; NULL
REMARK 3 TORSION ANGLES, PERIOD 1 (DEGREES): 297 ; 5.506 ; 5.000
REMARK 3 TORSION ANGLES, PERIOD 2 (DEGREES): 128 ;39.043 ;24.063
REMARK 3 TORSION ANGLES, PERIOD 3 (DEGREES): 472 ;14.574 ;15.000
REMARK 3 TORSION ANGLES, PERIOD 4 (DEGREES): 20 ;21.842 ;15.000
REMARK 3 CHIRAL-CENTER RESTRAINTS (A**3): 357 ; 0.096 ; 0.200
REMARK 3 GENERAL PLANES REFINED ATOMS (A): 1945 ; 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): 1188 ; 5.120 ; 5.240
REMARK 3 MAIN-CHAIN BOND OTHER ATOMS (A**2): NULL ; NULL ; NULL
REMARK 3 MAIN-CHAIN ANGLE REFINED ATOMS (A**2): 1485 ; 6.102 ; 9.929
REMARK 3 MAIN-CHAIN ANGLE OTHER ATOMS (A**2): NULL ; NULL ; NULL
REMARK 3 SIDE-CHAIN BOND REFINED ATOMS (A**2): 1353 ; 8.788 ; 7.143
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): 3779 ;11.903 ;31.828
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 : 1.40
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
REMARK 4
REMARK 4 5WEV COMPLIES WITH FORMAT V. 3.30, 13-JUL-11
REMARK 100
REMARK 100 THIS ENTRY HAS BEEN PROCESSED BY RCSB ON 12-JUL-17.
REMARK 100 THE DEPOSITION ID IS D_1000228675.
REMARK 200
REMARK 200 EXPERIMENTAL DETAILS
REMARK 200 EXPERIMENT TYPE : X-RAY DIFFRACTION
REMARK 200 DATE OF DATA COLLECTION : 10-OCT-09
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 : ALS
REMARK 200 BEAMLINE : 5.0.2
REMARK 200 X-RAY GENERATOR MODEL : NULL
REMARK 200 MONOCHROMATIC OR LAUE (M/L) : M
REMARK 200 WAVELENGTH OR RANGE (A) : 1.0
REMARK 200 MONOCHROMATOR : SI(111)
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 : SCALEPACK
REMARK 200
REMARK 200 NUMBER OF UNIQUE REFLECTIONS : 31177
REMARK 200 RESOLUTION RANGE HIGH (A) : 1.854
REMARK 200 RESOLUTION RANGE LOW (A) : 50.010
REMARK 200 REJECTION CRITERIA (SIGMA(I)) : 2.000
REMARK 200
REMARK 200 OVERALL.
REMARK 200 COMPLETENESS FOR RANGE (%) : 99.8
REMARK 200 DATA REDUNDANCY : 3.600
REMARK 200 R MERGE (I) : NULL
REMARK 200 R SYM (I) : 0.06700
REMARK 200 <I/SIGMA(I)> FOR THE DATA SET : 19.1000
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) : 1.92
REMARK 200 COMPLETENESS FOR SHELL (%) : 99.7
REMARK 200 DATA REDUNDANCY IN SHELL : 3.60
REMARK 200 R MERGE FOR SHELL (I) : NULL
REMARK 200 R SYM FOR SHELL (I) : 0.42400
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: PHASER
REMARK 200 STARTING MODEL: 2B7A
REMARK 200
REMARK 200 REMARK: RODS
REMARK 280
REMARK 280 CRYSTAL
REMARK 280 SOLVENT CONTENT, VS (%): 50.89
REMARK 280 MATTHEWS COEFFICIENT, VM (ANGSTROMS**3/DA): 2.50
REMARK 280
REMARK 280 CRYSTALLIZATION CONDITIONS: 25-30% W/V PEG 8000 0.2M AMMONIUM
REMARK 280 ACETATE 0.1M NA CITRATE PH 6.0, VAPOR DIFFUSION, HANGING DROP,
REMARK 280 TEMPERATURE 291K
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 53.82650
REMARK 290 SMTRY2 3 0.000000 1.000000 0.000000 34.77100
REMARK 290 SMTRY3 3 0.000000 0.000000 1.000000 0.00000
REMARK 290 SMTRY1 4 -1.000000 0.000000 0.000000 53.82650
REMARK 290 SMTRY2 4 0.000000 1.000000 0.000000 34.77100
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 MET A 814
REMARK 465 GLY A 815
REMARK 465 SER A 816
REMARK 465 SER A 817
REMARK 465 HIS A 818
REMARK 465 HIS A 819
REMARK 465 HIS A 820
REMARK 465 HIS A 821
REMARK 465 HIS A 822
REMARK 465 HIS A 823
REMARK 465 SER A 824
REMARK 465 SER A 825
REMARK 465 GLY A 826
REMARK 465 LEU A 827
REMARK 465 VAL A 828
REMARK 465 PRO A 829
REMARK 465 ARG A 830
REMARK 465 GLY A 831
REMARK 465 SER A 832
REMARK 465 GLY A 858
REMARK 465 ASN A 859
REMARK 465 PHE A 860
REMARK 465 ALA A 1131
REMARK 465 GLY A 1132
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 ASP A 840 87.67 -150.49
REMARK 500 GLN A 872 15.71 59.70
REMARK 500 THR A 875 -143.25 -119.63
REMARK 500 ARG A 975 -5.34 71.47
REMARK 500 ASP A 976 35.06 -140.09
REMARK 500 TYR A1050 29.22 48.69
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 9ZS A 1201
DBREF 5WEV A 833 1132 UNP O60674 JAK2_HUMAN 833 1132
SEQADV 5WEV MET A 814 UNP O60674 EXPRESSION TAG
SEQADV 5WEV GLY A 815 UNP O60674 EXPRESSION TAG
SEQADV 5WEV SER A 816 UNP O60674 EXPRESSION TAG
SEQADV 5WEV SER A 817 UNP O60674 EXPRESSION TAG
SEQADV 5WEV HIS A 818 UNP O60674 EXPRESSION TAG
SEQADV 5WEV HIS A 819 UNP O60674 EXPRESSION TAG
SEQADV 5WEV HIS A 820 UNP O60674 EXPRESSION TAG
SEQADV 5WEV HIS A 821 UNP O60674 EXPRESSION TAG
SEQADV 5WEV HIS A 822 UNP O60674 EXPRESSION TAG
SEQADV 5WEV HIS A 823 UNP O60674 EXPRESSION TAG
SEQADV 5WEV SER A 824 UNP O60674 EXPRESSION TAG
SEQADV 5WEV SER A 825 UNP O60674 EXPRESSION TAG
SEQADV 5WEV GLY A 826 UNP O60674 EXPRESSION TAG
SEQADV 5WEV LEU A 827 UNP O60674 EXPRESSION TAG
SEQADV 5WEV VAL A 828 UNP O60674 EXPRESSION TAG
SEQADV 5WEV PRO A 829 UNP O60674 EXPRESSION TAG
SEQADV 5WEV ARG A 830 UNP O60674 EXPRESSION TAG
SEQADV 5WEV GLY A 831 UNP O60674 EXPRESSION TAG
SEQADV 5WEV SER A 832 UNP O60674 EXPRESSION TAG
SEQRES 1 A 319 MET GLY SER SER HIS HIS HIS HIS HIS HIS SER SER GLY
SEQRES 2 A 319 LEU VAL PRO ARG GLY SER SER GLY ALA PHE GLU ASP ARG
SEQRES 3 A 319 ASP PRO THR GLN PHE GLU GLU ARG HIS LEU LYS PHE LEU
SEQRES 4 A 319 GLN GLN LEU GLY LYS GLY ASN PHE GLY SER VAL GLU MET
SEQRES 5 A 319 CYS ARG TYR ASP PRO LEU GLN ASP ASN THR GLY GLU VAL
SEQRES 6 A 319 VAL ALA VAL LYS LYS LEU GLN HIS SER THR GLU GLU HIS
SEQRES 7 A 319 LEU ARG ASP PHE GLU ARG GLU ILE GLU ILE LEU LYS SER
SEQRES 8 A 319 LEU GLN HIS ASP ASN ILE VAL LYS TYR LYS GLY VAL CYS
SEQRES 9 A 319 TYR SER ALA GLY ARG ARG ASN LEU LYS LEU ILE MET GLU
SEQRES 10 A 319 TYR LEU PRO TYR GLY SER LEU ARG ASP TYR LEU GLN LYS
SEQRES 11 A 319 HIS LYS GLU ARG ILE ASP HIS ILE LYS LEU LEU GLN TYR
SEQRES 12 A 319 THR SER GLN ILE CYS LYS GLY MET GLU TYR LEU GLY THR
SEQRES 13 A 319 LYS ARG TYR ILE HIS ARG ASP LEU ALA THR ARG ASN ILE
SEQRES 14 A 319 LEU VAL GLU ASN GLU ASN ARG VAL LYS ILE GLY ASP PHE
SEQRES 15 A 319 GLY LEU THR LYS VAL LEU PRO GLN ASP LYS GLU PTR PTR
SEQRES 16 A 319 LYS VAL LYS GLU PRO GLY GLU SER PRO ILE PHE TRP TYR
SEQRES 17 A 319 ALA PRO GLU SER LEU THR GLU SER LYS PHE SER VAL ALA
SEQRES 18 A 319 SER ASP VAL TRP SER PHE GLY VAL VAL LEU TYR GLU LEU
SEQRES 19 A 319 PHE THR TYR ILE GLU LYS SER LYS SER PRO PRO ALA GLU
SEQRES 20 A 319 PHE MET ARG MET ILE GLY ASN ASP LYS GLN GLY GLN MET
SEQRES 21 A 319 ILE VAL PHE HIS LEU ILE GLU LEU LEU LYS ASN ASN GLY
SEQRES 22 A 319 ARG LEU PRO ARG PRO ASP GLY CYS PRO ASP GLU ILE TYR
SEQRES 23 A 319 MET ILE MET THR GLU CYS TRP ASN ASN ASN VAL ASN GLN
SEQRES 24 A 319 ARG PRO SER PHE ARG ASP LEU ALA LEU ARG VAL ASP GLN
SEQRES 25 A 319 ILE ARG ASP ASN MET ALA GLY
MODRES 5WEV PTR A 1007 TYR MODIFIED RESIDUE
MODRES 5WEV PTR A 1008 TYR MODIFIED RESIDUE
HET PTR A1007 16
HET PTR A1008 16
HET 9ZS A1201 23
HETNAM PTR O-PHOSPHOTYROSINE
HETNAM 9ZS N-[2-(2,6-DICHLOROPHENYL)-1H-IMIDAZO[4,5-C]PYRIDIN-4-
HETNAM 2 9ZS YL]CYCLOPROPANECARBOXAMIDE
HETSYN PTR PHOSPHONOTYROSINE
FORMUL 1 PTR 2(C9 H12 N O6 P)
FORMUL 2 9ZS C16 H12 CL2 N4 O
FORMUL 3 HOH *139(H2 O)
HELIX 1 AA1 GLU A 845 ARG A 847 5 3
HELIX 2 AA2 THR A 888 SER A 904 1 17
HELIX 3 AA3 TYR A 918 ARG A 923 1 6
HELIX 4 AA4 SER A 936 HIS A 944 1 9
HELIX 5 AA5 LYS A 945 ILE A 948 5 4
HELIX 6 AA6 ASP A 949 LYS A 970 1 22
HELIX 7 AA7 ALA A 978 ARG A 980 5 3
HELIX 8 AA8 PRO A 1017 TYR A 1021 5 5
HELIX 9 AA9 ALA A 1022 SER A 1029 1 8
HELIX 10 AB1 SER A 1032 THR A 1049 1 18
HELIX 11 AB2 GLU A 1052 LYS A 1055 5 4
HELIX 12 AB3 SER A 1056 GLY A 1066 1 11
HELIX 13 AB4 GLY A 1071 ASN A 1084 1 14
HELIX 14 AB5 PRO A 1095 TRP A 1106 1 12
HELIX 15 AB6 ASN A 1109 ARG A 1113 5 5
HELIX 16 AB7 SER A 1115 ASN A 1129 1 15
SHEET 1 AA1 5 LEU A 849 GLY A 856 0
SHEET 2 AA1 5 SER A 862 TYR A 868 -1 O ARG A 867 N LYS A 850
SHEET 3 AA1 5 GLU A 877 LYS A 883 -1 O VAL A 881 N GLU A 864
SHEET 4 AA1 5 LYS A 926 GLU A 930 -1 O MET A 929 N ALA A 880
SHEET 5 AA1 5 TYR A 913 CYS A 917 -1 N GLY A 915 O ILE A 928
SHEET 1 AA2 2 TYR A 972 ILE A 973 0
SHEET 2 AA2 2 LYS A 999 VAL A1000 -1 O LYS A 999 N ILE A 973
SHEET 1 AA3 2 ILE A 982 ASN A 986 0
SHEET 2 AA3 2 ARG A 989 ILE A 992 -1 O LYS A 991 N LEU A 983
SHEET 1 AA4 2 PTR A1008 LYS A1009 0
SHEET 2 AA4 2 LYS A1030 PHE A1031 -1 O PHE A1031 N PTR A1008
LINK C GLU A1006 N PTR A1007 1555 1555 1.34
LINK C PTR A1007 N PTR A1008 1555 1555 1.33
LINK C PTR A1008 N LYS A1009 1555 1555 1.33
SITE 1 AC1 12 GLN A 853 LEU A 855 ALA A 880 GLU A 930
SITE 2 AC1 12 TYR A 931 LEU A 932 PRO A 933 GLY A 935
SITE 3 AC1 12 LEU A 983 HOH A1359 HOH A1370 HOH A1411
CRYST1 107.653 69.542 50.629 90.00 98.93 90.00 C 1 2 1 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 0.009289 0.000000 0.001460 0.00000
SCALE2 0.000000 0.014380 0.000000 0.00000
SCALE3 0.000000 0.000000 0.019994 0.00000
(ATOM LINES ARE NOT SHOWN.)
END
