HEADER TRANSFERASE/TRANSFERASE INHIBITOR 09-MAR-15 4YNE
TITLE (R)-2-PHENYLPYRROLIDINE SUBSTITUTE IMIDAZOPYRIDAZINES: A NEW CLASS OF
TITLE 2 POTENT AND SELECTIVE PAN-TRK INHIBITORS
COMPND MOL_ID: 1;
COMPND 2 MOLECULE: HIGH AFFINITY NERVE GROWTH FACTOR RECEPTOR;
COMPND 3 CHAIN: A;
COMPND 4 SYNONYM: NEUROTROPHIC TYROSINE KINASE RECEPTOR TYPE 1,TRK1-
COMPND 5 TRANSFORMING TYROSINE KINASE PROTEIN,TROPOMYOSIN-RELATED KINASE A,
COMPND 6 TYROSINE KINASE RECEPTOR,TYROSINE KINASE RECEPTOR A,TRK-A,GP140TRK,
COMPND 7 P140-TRKA;
COMPND 8 EC: 2.7.10.1;
COMPND 9 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: NTRK1, MTC, TRK, TRKA;
SOURCE 6 EXPRESSION_SYSTEM: SPODOPTERA FRUGIPERDA;
SOURCE 7 EXPRESSION_SYSTEM_TAXID: 7108;
SOURCE 8 EXPRESSION_SYSTEM_CELL_LINE: SF9;
SOURCE 9 EXPRESSION_SYSTEM_VECTOR_TYPE: BACULOVIRUS;
SOURCE 10 EXPRESSION_SYSTEM_PLASMID: PFASTBAC1-HM
KEYWDS KINASE, TRK, INHIBITOR, ONCOLOGY, TRANSFERASE-TRANSFERASE INHIBITOR
KEYWDS 2 COMPLEX
EXPDTA X-RAY DIFFRACTION
AUTHOR A.KREUSCH,P.RUCKER,V.MOLTENI,J.LOREN
REVDAT 2 27-SEP-23 4YNE 1 SOURCE REMARK
REVDAT 1 03-JUN-15 4YNE 0
JRNL AUTH H.S.CHOI,P.V.RUCKER,Z.WANG,Y.FAN,P.ALBAUGH,G.CHOPIUK,
JRNL AUTH 2 F.GESSIER,F.SUN,F.ADRIAN,G.LIU,T.HOOD,N.LI,Y.JIA,J.CHE,
JRNL AUTH 3 S.MCCORMACK,A.LI,J.LI,A.STEFFY,A.CULAZZO,C.TOMPKINS,V.PHUNG,
JRNL AUTH 4 A.KREUSCH,M.LU,B.HU,A.CHAUDHARY,M.PRASHAD,T.TUNTLAND,B.LIU,
JRNL AUTH 5 J.HARRIS,H.M.SEIDEL,J.LOREN,V.MOLTENI
JRNL TITL (R)-2-PHENYLPYRROLIDINE SUBSTITUTED IMIDAZOPYRIDAZINES: A
JRNL TITL 2 NEW CLASS OF POTENT AND SELECTIVE PAN-TRK INHIBITORS.
JRNL REF ACS MED.CHEM.LETT. V. 6 562 2015
JRNL REFN ISSN 1948-5875
JRNL PMID 26005534
JRNL DOI 10.1021/ACSMEDCHEMLETT.5B00050
REMARK 2
REMARK 2 RESOLUTION. 2.02 ANGSTROMS.
REMARK 3
REMARK 3 REFINEMENT.
REMARK 3 PROGRAM : PHENIX (PHENIX.REFINE: 1.9_1692)
REMARK 3 AUTHORS : PAUL ADAMS,PAVEL AFONINE,VINCENT CHEN,IAN
REMARK 3 : DAVIS,KRESHNA GOPAL,RALF GROSSE-KUNSTLEVE,
REMARK 3 : LI-WEI HUNG,ROBERT IMMORMINO,TOM IOERGER,
REMARK 3 : AIRLIE MCCOY,ERIK MCKEE,NIGEL MORIARTY,
REMARK 3 : REETAL PAI,RANDY READ,JANE RICHARDSON,
REMARK 3 : DAVID RICHARDSON,TOD ROMO,JIM SACCHETTINI,
REMARK 3 : NICHOLAS SAUTER,JACOB SMITH,LAURENT
REMARK 3 : STORONI,TOM TERWILLIGER,PETER ZWART
REMARK 3
REMARK 3 REFINEMENT TARGET : ML
REMARK 3
REMARK 3 DATA USED IN REFINEMENT.
REMARK 3 RESOLUTION RANGE HIGH (ANGSTROMS) : 2.02
REMARK 3 RESOLUTION RANGE LOW (ANGSTROMS) : 34.13
REMARK 3 MIN(FOBS/SIGMA_FOBS) : 1.350
REMARK 3 COMPLETENESS FOR RANGE (%) : 99.7
REMARK 3 NUMBER OF REFLECTIONS : 28997
REMARK 3
REMARK 3 FIT TO DATA USED IN REFINEMENT.
REMARK 3 R VALUE (WORKING + TEST SET) : 0.185
REMARK 3 R VALUE (WORKING SET) : 0.183
REMARK 3 FREE R VALUE : 0.216
REMARK 3 FREE R VALUE TEST SET SIZE (%) : 5.080
REMARK 3 FREE R VALUE TEST SET COUNT : 1474
REMARK 3
REMARK 3 FIT TO DATA USED IN REFINEMENT (IN BINS).
REMARK 3 BIN RESOLUTION RANGE COMPL. NWORK NFREE RWORK RFREE
REMARK 3 1 34.1000 - 4.4957 0.99 2617 116 0.1734 0.2204
REMARK 3 2 4.4957 - 3.5696 1.00 2548 126 0.1586 0.1623
REMARK 3 3 3.5696 - 3.1187 1.00 2501 148 0.1901 0.2184
REMARK 3 4 3.1187 - 2.8337 1.00 2512 139 0.1934 0.2379
REMARK 3 5 2.8337 - 2.6307 1.00 2519 126 0.2013 0.2605
REMARK 3 6 2.6307 - 2.4757 1.00 2443 149 0.1931 0.2156
REMARK 3 7 2.4757 - 2.3517 1.00 2483 128 0.1982 0.2833
REMARK 3 8 2.3517 - 2.2493 1.00 2477 138 0.2089 0.2304
REMARK 3 9 2.2493 - 2.1628 1.00 2491 143 0.2150 0.2532
REMARK 3 10 2.1628 - 2.0882 1.00 2457 126 0.2305 0.2481
REMARK 3 11 2.0882 - 2.0229 0.99 2475 135 0.2562 0.2874
REMARK 3
REMARK 3 BULK SOLVENT MODELLING.
REMARK 3 METHOD USED : FLAT BULK SOLVENT MODEL
REMARK 3 SOLVENT RADIUS : 1.11
REMARK 3 SHRINKAGE RADIUS : 0.90
REMARK 3 K_SOL : NULL
REMARK 3 B_SOL : NULL
REMARK 3
REMARK 3 ERROR ESTIMATES.
REMARK 3 COORDINATE ERROR (MAXIMUM-LIKELIHOOD BASED) : 0.200
REMARK 3 PHASE ERROR (DEGREES, MAXIMUM-LIKELIHOOD BASED) : 23.150
REMARK 3
REMARK 3 B VALUES.
REMARK 3 FROM WILSON PLOT (A**2) : 45.64
REMARK 3 MEAN B VALUE (OVERALL, A**2) : 56.66
REMARK 3 OVERALL ANISOTROPIC B VALUE.
REMARK 3 B11 (A**2) : NULL
REMARK 3 B22 (A**2) : NULL
REMARK 3 B33 (A**2) : NULL
REMARK 3 B12 (A**2) : NULL
REMARK 3 B13 (A**2) : NULL
REMARK 3 B23 (A**2) : NULL
REMARK 3
REMARK 3 TWINNING INFORMATION.
REMARK 3 FRACTION: NULL
REMARK 3 OPERATOR: NULL
REMARK 3
REMARK 3 DEVIATIONS FROM IDEAL VALUES.
REMARK 3 RMSD COUNT
REMARK 3 BOND : 0.008 2314
REMARK 3 ANGLE : 1.057 3141
REMARK 3 CHIRALITY : 0.050 335
REMARK 3 PLANARITY : 0.005 399
REMARK 3 DIHEDRAL : 13.982 816
REMARK 3
REMARK 3 TLS DETAILS
REMARK 3 NUMBER OF TLS GROUPS : 1
REMARK 3 TLS GROUP : 1
REMARK 3 SELECTION: ALL
REMARK 3 ORIGIN FOR THE GROUP (A): -25.6387 -42.9463 -19.4055
REMARK 3 T TENSOR
REMARK 3 T11: 0.3802 T22: 0.2920
REMARK 3 T33: 0.2725 T12: 0.0466
REMARK 3 T13: 0.0393 T23: -0.0233
REMARK 3 L TENSOR
REMARK 3 L11: 4.2519 L22: 1.9296
REMARK 3 L33: 4.0990 L12: 0.7625
REMARK 3 L13: 0.8591 L23: 0.1315
REMARK 3 S TENSOR
REMARK 3 S11: -0.2090 S12: -0.0792 S13: 0.0846
REMARK 3 S21: -0.1791 S22: -0.0313 S23: 0.0772
REMARK 3 S31: -0.3414 S32: 0.1636 S33: 0.1902
REMARK 3
REMARK 3 NCS DETAILS
REMARK 3 NUMBER OF NCS GROUPS : NULL
REMARK 3
REMARK 3 OTHER REFINEMENT REMARKS: NULL
REMARK 4
REMARK 4 4YNE COMPLIES WITH FORMAT V. 3.30, 13-JUL-11
REMARK 100
REMARK 100 THIS ENTRY HAS BEEN PROCESSED BY RCSB ON 10-MAR-15.
REMARK 100 THE DEPOSITION ID IS D_1000207752.
REMARK 200
REMARK 200 EXPERIMENTAL DETAILS
REMARK 200 EXPERIMENT TYPE : X-RAY DIFFRACTION
REMARK 200 DATE OF DATA COLLECTION : 28-APR-12
REMARK 200 TEMPERATURE (KELVIN) : 100
REMARK 200 PH : 5.0
REMARK 200 NUMBER OF CRYSTALS USED : 1
REMARK 200
REMARK 200 SYNCHROTRON (Y/N) : Y
REMARK 200 RADIATION SOURCE : ALS
REMARK 200 BEAMLINE : 5.0.3
REMARK 200 X-RAY GENERATOR MODEL : NULL
REMARK 200 MONOCHROMATIC OR LAUE (M/L) : M
REMARK 200 WAVELENGTH OR RANGE (A) : 0.9765
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 : DENZO
REMARK 200 DATA SCALING SOFTWARE : HKL-2000
REMARK 200
REMARK 200 NUMBER OF UNIQUE REFLECTIONS : 29032
REMARK 200 RESOLUTION RANGE HIGH (A) : 2.020
REMARK 200 RESOLUTION RANGE LOW (A) : 34.130
REMARK 200 REJECTION CRITERIA (SIGMA(I)) : NULL
REMARK 200
REMARK 200 OVERALL.
REMARK 200 COMPLETENESS FOR RANGE (%) : 99.8
REMARK 200 DATA REDUNDANCY : 5.600
REMARK 200 R MERGE (I) : 0.03500
REMARK 200 R SYM (I) : NULL
REMARK 200 <I/SIGMA(I)> FOR THE DATA SET : 12.3000
REMARK 200
REMARK 200 IN THE HIGHEST RESOLUTION SHELL.
REMARK 200 HIGHEST RESOLUTION SHELL, RANGE HIGH (A) : 2.02
REMARK 200 HIGHEST RESOLUTION SHELL, RANGE LOW (A) : 2.05
REMARK 200 COMPLETENESS FOR SHELL (%) : 100.0
REMARK 200 DATA REDUNDANCY IN SHELL : 5.10
REMARK 200 R MERGE FOR SHELL (I) : 0.57500
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: 3V5Q
REMARK 200
REMARK 200 REMARK: NULL
REMARK 280
REMARK 280 CRYSTAL
REMARK 280 SOLVENT CONTENT, VS (%): 62.00
REMARK 280 MATTHEWS COEFFICIENT, VM (ANGSTROMS**3/DA): 3.23
REMARK 280
REMARK 280 CRYSTALLIZATION CONDITIONS: 0.8M (NH4)2SO4, 0.1M CITRATE PH 5.0,
REMARK 280 VAPOR DIFFUSION, SITTING DROP, TEMPERATURE 277K
REMARK 290
REMARK 290 CRYSTALLOGRAPHIC SYMMETRY
REMARK 290 SYMMETRY OPERATORS FOR SPACE GROUP: H 3 2
REMARK 290
REMARK 290 SYMOP SYMMETRY
REMARK 290 NNNMMM OPERATOR
REMARK 290 1555 X,Y,Z
REMARK 290 2555 -Y,X-Y,Z
REMARK 290 3555 -X+Y,-X,Z
REMARK 290 4555 Y,X,-Z
REMARK 290 5555 X-Y,-Y,-Z
REMARK 290 6555 -X,-X+Y,-Z
REMARK 290 7555 X+2/3,Y+1/3,Z+1/3
REMARK 290 8555 -Y+2/3,X-Y+1/3,Z+1/3
REMARK 290 9555 -X+Y+2/3,-X+1/3,Z+1/3
REMARK 290 10555 Y+2/3,X+1/3,-Z+1/3
REMARK 290 11555 X-Y+2/3,-Y+1/3,-Z+1/3
REMARK 290 12555 -X+2/3,-X+Y+1/3,-Z+1/3
REMARK 290 13555 X+1/3,Y+2/3,Z+2/3
REMARK 290 14555 -Y+1/3,X-Y+2/3,Z+2/3
REMARK 290 15555 -X+Y+1/3,-X+2/3,Z+2/3
REMARK 290 16555 Y+1/3,X+2/3,-Z+2/3
REMARK 290 17555 X-Y+1/3,-Y+2/3,-Z+2/3
REMARK 290 18555 -X+1/3,-X+Y+2/3,-Z+2/3
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 -0.500000 -0.866025 0.000000 0.00000
REMARK 290 SMTRY2 2 0.866025 -0.500000 0.000000 0.00000
REMARK 290 SMTRY3 2 0.000000 0.000000 1.000000 0.00000
REMARK 290 SMTRY1 3 -0.500000 0.866025 0.000000 0.00000
REMARK 290 SMTRY2 3 -0.866025 -0.500000 0.000000 0.00000
REMARK 290 SMTRY3 3 0.000000 0.000000 1.000000 0.00000
REMARK 290 SMTRY1 4 -0.500000 0.866025 0.000000 0.00000
REMARK 290 SMTRY2 4 0.866025 0.500000 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 0.00000
REMARK 290 SMTRY2 5 0.000000 -1.000000 0.000000 0.00000
REMARK 290 SMTRY3 5 0.000000 0.000000 -1.000000 0.00000
REMARK 290 SMTRY1 6 -0.500000 -0.866025 0.000000 0.00000
REMARK 290 SMTRY2 6 -0.866025 0.500000 0.000000 0.00000
REMARK 290 SMTRY3 6 0.000000 0.000000 -1.000000 0.00000
REMARK 290 SMTRY1 7 1.000000 0.000000 0.000000 52.87350
REMARK 290 SMTRY2 7 0.000000 1.000000 0.000000 30.52653
REMARK 290 SMTRY3 7 0.000000 0.000000 1.000000 68.22800
REMARK 290 SMTRY1 8 -0.500000 -0.866025 0.000000 52.87350
REMARK 290 SMTRY2 8 0.866025 -0.500000 0.000000 30.52653
REMARK 290 SMTRY3 8 0.000000 0.000000 1.000000 68.22800
REMARK 290 SMTRY1 9 -0.500000 0.866025 0.000000 52.87350
REMARK 290 SMTRY2 9 -0.866025 -0.500000 0.000000 30.52653
REMARK 290 SMTRY3 9 0.000000 0.000000 1.000000 68.22800
REMARK 290 SMTRY1 10 -0.500000 0.866025 0.000000 52.87350
REMARK 290 SMTRY2 10 0.866025 0.500000 0.000000 30.52653
REMARK 290 SMTRY3 10 0.000000 0.000000 -1.000000 68.22800
REMARK 290 SMTRY1 11 1.000000 0.000000 0.000000 52.87350
REMARK 290 SMTRY2 11 0.000000 -1.000000 0.000000 30.52653
REMARK 290 SMTRY3 11 0.000000 0.000000 -1.000000 68.22800
REMARK 290 SMTRY1 12 -0.500000 -0.866025 0.000000 52.87350
REMARK 290 SMTRY2 12 -0.866025 0.500000 0.000000 30.52653
REMARK 290 SMTRY3 12 0.000000 0.000000 -1.000000 68.22800
REMARK 290 SMTRY1 13 1.000000 0.000000 0.000000 0.00000
REMARK 290 SMTRY2 13 0.000000 1.000000 0.000000 61.05306
REMARK 290 SMTRY3 13 0.000000 0.000000 1.000000 136.45600
REMARK 290 SMTRY1 14 -0.500000 -0.866025 0.000000 0.00000
REMARK 290 SMTRY2 14 0.866025 -0.500000 0.000000 61.05306
REMARK 290 SMTRY3 14 0.000000 0.000000 1.000000 136.45600
REMARK 290 SMTRY1 15 -0.500000 0.866025 0.000000 0.00000
REMARK 290 SMTRY2 15 -0.866025 -0.500000 0.000000 61.05306
REMARK 290 SMTRY3 15 0.000000 0.000000 1.000000 136.45600
REMARK 290 SMTRY1 16 -0.500000 0.866025 0.000000 0.00000
REMARK 290 SMTRY2 16 0.866025 0.500000 0.000000 61.05306
REMARK 290 SMTRY3 16 0.000000 0.000000 -1.000000 136.45600
REMARK 290 SMTRY1 17 1.000000 0.000000 0.000000 0.00000
REMARK 290 SMTRY2 17 0.000000 -1.000000 0.000000 61.05306
REMARK 290 SMTRY3 17 0.000000 0.000000 -1.000000 136.45600
REMARK 290 SMTRY1 18 -0.500000 -0.866025 0.000000 0.00000
REMARK 290 SMTRY2 18 -0.866025 0.500000 0.000000 61.05306
REMARK 290 SMTRY3 18 0.000000 0.000000 -1.000000 136.45600
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 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 GLY A -7
REMARK 465 ALA A -6
REMARK 465 MET A -5
REMARK 465 GLU A 535
REMARK 465 GLN A 536
REMARK 465 ALA A 549
REMARK 465 SER A 550
REMARK 465 GLU A 551
REMARK 465 SER A 552
REMARK 465 ALA A 553
REMARK 465 SER A 672
REMARK 465 ARG A 673
REMARK 465 ASP A 674
REMARK 465 ILE A 675
REMARK 465 TYR A 676
REMARK 465 VAL A 683
REMARK 465 GLY A 684
REMARK 465 GLY A 685
REMARK 465 ARG A 686
REMARK 465 VAL A 794
REMARK 465 LEU A 795
REMARK 465 GLY A 796
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 LYS A 506 CG CD CE NZ
REMARK 470 ASP A 537 CG OD1 OD2
REMARK 470 LYS A 538 CG CD CE NZ
REMARK 470 LYS A 547 CG CD CE NZ
REMARK 470 GLU A 548 CG CD OE1 OE2
REMARK 470 ARG A 554 CG CD NE CZ NH1 NH2
REMARK 470 GLN A 555 CG CD OE1 NE2
REMARK 470 ARG A 583 CG CD NE CZ NH1 NH2
REMARK 470 ASP A 607 CG OD1 OD2
REMARK 470 LYS A 609 CG CD CE NZ
REMARK 470 LEU A 611 CG CD1 CD2
REMARK 470 ARG A 702 CG CD NE CZ NH1 NH2
REMARK 470 ARG A 750 CG CD NE CZ NH1 NH2
REMARK 470 GLN A 769 CG CD OE1 NE2
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 LEU A 532 -66.39 -91.27
REMARK 500 LYS A 547 -70.32 -59.96
REMARK 500 ASP A 650 53.77 -150.12
REMARK 500 ALA A 787 78.94 -151.78
REMARK 500
REMARK 500 REMARK: NULL
REMARK 525
REMARK 525 SOLVENT
REMARK 525
REMARK 525 THE SOLVENT MOLECULES HAVE CHAIN IDENTIFIERS THAT
REMARK 525 INDICATE THE POLYMER CHAIN WITH WHICH THEY ARE MOST
REMARK 525 CLOSELY ASSOCIATED. THE REMARK LISTS ALL THE SOLVENT
REMARK 525 MOLECULES WHICH ARE MORE THAN 5A AWAY FROM THE
REMARK 525 NEAREST POLYMER CHAIN (M = MODEL NUMBER;
REMARK 525 RES=RESIDUE NAME; C=CHAIN IDENTIFIER; SSEQ=SEQUENCE
REMARK 525 NUMBER; I=INSERTION CODE):
REMARK 525
REMARK 525 M RES CSSEQI
REMARK 525 HOH A 949 DISTANCE = 6.40 ANGSTROMS
REMARK 800
REMARK 800 SITE
REMARK 800 SITE_IDENTIFIER: AC1
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: binding site for residue 4EK A 801
REMARK 800
REMARK 800 SITE_IDENTIFIER: AC2
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: binding site for residue SO4 A 802
REMARK 800
REMARK 800 SITE_IDENTIFIER: AC3
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: binding site for residue SO4 A 803
REMARK 800
REMARK 800 SITE_IDENTIFIER: AC4
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: binding site for residue SO4 A 804
REMARK 800
REMARK 800 SITE_IDENTIFIER: AC5
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: binding site for residue SO4 A 805
REMARK 800
REMARK 800 SITE_IDENTIFIER: AC6
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: binding site for residue SO4 A 806
REMARK 800
REMARK 800 SITE_IDENTIFIER: AC7
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: binding site for residue GOL A 807
DBREF 4YNE A 502 796 UNP P04629 NTRK1_HUMAN 502 796
SEQADV 4YNE GLY A -7 UNP P04629 EXPRESSION TAG
SEQADV 4YNE ALA A -6 UNP P04629 EXPRESSION TAG
SEQADV 4YNE MET A -5 UNP P04629 EXPRESSION TAG
SEQADV 4YNE GLY A -4 UNP P04629 EXPRESSION TAG
SEQADV 4YNE SER A -3 UNP P04629 EXPRESSION TAG
SEQADV 4YNE GLY A -2 UNP P04629 EXPRESSION TAG
SEQADV 4YNE ILE A -1 UNP P04629 EXPRESSION TAG
SEQADV 4YNE ARG A 0 UNP P04629 EXPRESSION TAG
SEQRES 1 A 303 GLY ALA MET GLY SER GLY ILE ARG VAL HIS HIS ILE LYS
SEQRES 2 A 303 ARG ARG ASP ILE VAL LEU LYS TRP GLU LEU GLY GLU GLY
SEQRES 3 A 303 ALA PHE GLY LYS VAL PHE LEU ALA GLU CYS HIS ASN LEU
SEQRES 4 A 303 LEU PRO GLU GLN ASP LYS MET LEU VAL ALA VAL LYS ALA
SEQRES 5 A 303 LEU LYS GLU ALA SER GLU SER ALA ARG GLN ASP PHE GLN
SEQRES 6 A 303 ARG GLU ALA GLU LEU LEU THR MET LEU GLN HIS GLN HIS
SEQRES 7 A 303 ILE VAL ARG PHE PHE GLY VAL CYS THR GLU GLY ARG PRO
SEQRES 8 A 303 LEU LEU MET VAL PHE GLU TYR MET ARG HIS GLY ASP LEU
SEQRES 9 A 303 ASN ARG PHE LEU ARG SER HIS GLY PRO ASP ALA LYS LEU
SEQRES 10 A 303 LEU ALA GLY GLY GLU ASP VAL ALA PRO GLY PRO LEU GLY
SEQRES 11 A 303 LEU GLY GLN LEU LEU ALA VAL ALA SER GLN VAL ALA ALA
SEQRES 12 A 303 GLY MET VAL TYR LEU ALA GLY LEU HIS PHE VAL HIS ARG
SEQRES 13 A 303 ASP LEU ALA THR ARG ASN CYS LEU VAL GLY GLN GLY LEU
SEQRES 14 A 303 VAL VAL LYS ILE GLY ASP PHE GLY MET SER ARG ASP ILE
SEQRES 15 A 303 TYR SER THR ASP TYR TYR ARG VAL GLY GLY ARG THR MET
SEQRES 16 A 303 LEU PRO ILE ARG TRP MET PRO PRO GLU SER ILE LEU TYR
SEQRES 17 A 303 ARG LYS PHE THR THR GLU SER ASP VAL TRP SER PHE GLY
SEQRES 18 A 303 VAL VAL LEU TRP GLU ILE PHE THR TYR GLY LYS GLN PRO
SEQRES 19 A 303 TRP TYR GLN LEU SER ASN THR GLU ALA ILE ASP CYS ILE
SEQRES 20 A 303 THR GLN GLY ARG GLU LEU GLU ARG PRO ARG ALA CYS PRO
SEQRES 21 A 303 PRO GLU VAL TYR ALA ILE MET ARG GLY CYS TRP GLN ARG
SEQRES 22 A 303 GLU PRO GLN GLN ARG HIS SER ILE LYS ASP VAL HIS ALA
SEQRES 23 A 303 ARG LEU GLN ALA LEU ALA GLN ALA PRO PRO VAL TYR LEU
SEQRES 24 A 303 ASP VAL LEU GLY
HET 4EK A 801 27
HET SO4 A 802 5
HET SO4 A 803 5
HET SO4 A 804 5
HET SO4 A 805 5
HET SO4 A 806 5
HET GOL A 807 6
HETNAM 4EK 6-[(2R)-2-(3-FLUOROPHENYL)PYRROLIDIN-1-YL]-3-(PYRIDIN-
HETNAM 2 4EK 2-YL)IMIDAZO[1,2-B]PYRIDAZINE
HETNAM SO4 SULFATE ION
HETNAM GOL GLYCEROL
HETSYN GOL GLYCERIN; PROPANE-1,2,3-TRIOL
FORMUL 2 4EK C21 H18 F N5
FORMUL 3 SO4 5(O4 S 2-)
FORMUL 8 GOL C3 H8 O3
FORMUL 9 HOH *78(H2 O)
HELIX 1 AA1 LYS A 506 ARG A 508 5 3
HELIX 2 AA2 GLN A 555 LEU A 567 1 13
HELIX 3 AA3 ASP A 596 HIS A 604 1 9
HELIX 4 AA4 GLY A 623 LEU A 644 1 22
HELIX 5 AA5 ALA A 652 ARG A 654 5 3
HELIX 6 AA6 GLN A 660 LEU A 662 5 3
HELIX 7 AA7 PRO A 690 MET A 694 5 5
HELIX 8 AA8 PRO A 695 ARG A 702 1 8
HELIX 9 AA9 THR A 705 THR A 722 1 18
HELIX 10 AB1 SER A 732 GLY A 743 1 12
HELIX 11 AB2 PRO A 753 TRP A 764 1 12
HELIX 12 AB3 GLU A 767 ARG A 771 5 5
HELIX 13 AB4 SER A 773 ALA A 787 1 15
SHEET 1 AA1 5 ILE A 510 GLY A 519 0
SHEET 2 AA1 5 GLY A 522 CYS A 529 -1 O VAL A 524 N LEU A 516
SHEET 3 AA1 5 MET A 539 ALA A 545 -1 O VAL A 543 N PHE A 525
SHEET 4 AA1 5 LEU A 586 GLU A 590 -1 O PHE A 589 N ALA A 542
SHEET 5 AA1 5 PHE A 575 CYS A 579 -1 N PHE A 576 O VAL A 588
SHEET 1 AA2 2 CYS A 656 VAL A 658 0
SHEET 2 AA2 2 VAL A 664 ILE A 666 -1 O LYS A 665 N LEU A 657
CISPEP 1 HIS A 530 ASN A 531 0 -3.34
CISPEP 2 ARG A 583 PRO A 584 0 0.78
CISPEP 3 GLY A 613 GLY A 614 0 3.15
SITE 1 AC1 12 PHE A 521 ALA A 542 PHE A 589 GLU A 590
SITE 2 AC1 12 MET A 592 ARG A 654 ASN A 655 CYS A 656
SITE 3 AC1 12 LEU A 657 GLY A 667 ASP A 668 HOH A 930
SITE 1 AC2 4 THR A 722 LYS A 725 ARG A 750 HOH A 920
SITE 1 AC3 4 ARG A 0 HIS A 503 HIS A 504 HOH A 949
SITE 1 AC4 5 ARG A 602 ASP A 607 TYR A 723 LYS A 725
SITE 2 AC4 5 HOH A 973
SITE 1 AC5 3 GLN A 633 GLY A 661 LEU A 662
SITE 1 AC6 5 HIS A 571 SER A 632 GLN A 633 HIS A 778
SITE 2 AC6 5 GLN A 782
SITE 1 AC7 7 LYS A 544 GLU A 560 ASP A 668 PHE A 669
SITE 2 AC7 7 GLY A 670 MET A 671 HOH A 929
CRYST1 105.747 105.747 204.684 90.00 90.00 120.00 H 3 2 18
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 0.009457 0.005460 0.000000 0.00000
SCALE2 0.000000 0.010919 0.000000 0.00000
SCALE3 0.000000 0.000000 0.004886 0.00000
(ATOM LINES ARE NOT SHOWN.)
END
