HEADER TRANSFERASE/INHIBITOR 12-APR-18 6D20
TITLE CRYSTAL STRUCTURE OF TYROSINE-PROTEIN KINASE RECEPTOR IN COMPLEX WITH
TITLE 2 5-(4-FLUOROPHENYL)THIENO[2,3-D]PYRIMIDIN-4(3H)-ONE AND 5-{[2,4-
TITLE 3 DICHLORO-5-(PYRIDIN-2-YL)BENZENE-1-CARBONYL]AMINO}-N-(2-HYDROXY-2-
TITLE 4 METHYLPROPYL)-1-PHENYL-1H-PYRAZOLE-3-CARBOXAMIDE 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: INSECT CELL EXPRESSION VECTOR PTIE1;
SOURCE 7 EXPRESSION_SYSTEM_TAXID: 266783;
SOURCE 8 EXPRESSION_SYSTEM_VECTOR_TYPE: PKRIC-N6
KEYWDS ALLOSTERIC INHIBITOR COMPLEX TYROSINE KINASE, TRANSFERASE,
KEYWDS 2 TRANSFERASE-INHIBITOR COMPLEX
EXPDTA X-RAY DIFFRACTION
AUTHOR S.E.GREASLEY,E.JOHNSON,M.L.KRAUS,C.N.CRONIN
REVDAT 3 13-MAR-24 6D20 1 REMARK
REVDAT 2 01-MAY-19 6D20 1 JRNL
REVDAT 1 02-MAY-18 6D20 0
JRNL AUTH S.K.BAGAL,K.OMOTO,D.C.BLAKEMORE,P.J.BUNGAY,J.G.BILSLAND,
JRNL AUTH 2 P.J.CLARKE,M.S.CORBETT,C.N.CRONIN,J.J.CUI,R.DIAS,
JRNL AUTH 3 N.J.FLANAGAN,S.E.GREASLEY,R.GRIMLEY,E.JOHNSON,D.FENGAS,
JRNL AUTH 4 L.KITCHING,M.L.KRAUS,I.MCALPINE,A.NAGATA,G.J.WALDRON,
JRNL AUTH 5 J.S.WARMUS
JRNL TITL DISCOVERY OF ALLOSTERIC, POTENT, SUBTYPE SELECTIVE, AND
JRNL TITL 2 PERIPHERALLY RESTRICTED TRKA KINASE INHIBITORS.
JRNL REF J. MED. CHEM. V. 62 247 2019
JRNL REFN ISSN 1520-4804
JRNL PMID 29672039
JRNL DOI 10.1021/ACS.JMEDCHEM.8B00280
REMARK 2
REMARK 2 RESOLUTION. 1.94 ANGSTROMS.
REMARK 3
REMARK 3 REFINEMENT.
REMARK 3 PROGRAM : BUSTER
REMARK 3 AUTHORS : BRICOGNE,BLANC,BRANDL,FLENSBURG,KELLER,
REMARK 3 : PACIOREK,ROVERSI,SHARFF,SMART,VONRHEIN,
REMARK 3 : WOMACK,MATTHEWS,TEN EYCK,TRONRUD
REMARK 3
REMARK 3 DATA USED IN REFINEMENT.
REMARK 3 RESOLUTION RANGE HIGH (ANGSTROMS) : 1.94
REMARK 3 RESOLUTION RANGE LOW (ANGSTROMS) : 45.47
REMARK 3 DATA CUTOFF (SIGMA(F)) : 0.000
REMARK 3 COMPLETENESS FOR RANGE (%) : 97.8
REMARK 3 NUMBER OF REFLECTIONS : 23957
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) : 0.172
REMARK 3 R VALUE (WORKING SET) : 0.170
REMARK 3 FREE R VALUE : 0.207
REMARK 3 FREE R VALUE TEST SET SIZE (%) : 5.120
REMARK 3 FREE R VALUE TEST SET COUNT : 1226
REMARK 3 ESTIMATED ERROR OF FREE R VALUE : NULL
REMARK 3
REMARK 3 FIT IN THE HIGHEST RESOLUTION BIN.
REMARK 3 TOTAL NUMBER OF BINS USED : 12
REMARK 3 BIN RESOLUTION RANGE HIGH (ANGSTROMS) : 1.94
REMARK 3 BIN RESOLUTION RANGE LOW (ANGSTROMS) : 2.03
REMARK 3 BIN COMPLETENESS (WORKING+TEST) (%) : 97.77
REMARK 3 REFLECTIONS IN BIN (WORKING + TEST SET) : 2715
REMARK 3 BIN R VALUE (WORKING + TEST SET) : 0.1984
REMARK 3 REFLECTIONS IN BIN (WORKING SET) : 2586
REMARK 3 BIN R VALUE (WORKING SET) : 0.1966
REMARK 3 BIN FREE R VALUE : 0.2318
REMARK 3 BIN FREE R VALUE TEST SET SIZE (%) : 4.75
REMARK 3 BIN FREE R VALUE TEST SET COUNT : 129
REMARK 3 ESTIMATED ERROR OF BIN FREE R VALUE : 0.000
REMARK 3
REMARK 3 NUMBER OF NON-HYDROGEN ATOMS USED IN REFINEMENT.
REMARK 3 PROTEIN ATOMS : 2352
REMARK 3 NUCLEIC ACID ATOMS : 0
REMARK 3 HETEROGEN ATOMS : 53
REMARK 3 SOLVENT ATOMS : 224
REMARK 3
REMARK 3 B VALUES.
REMARK 3 FROM WILSON PLOT (A**2) : 23.60
REMARK 3 MEAN B VALUE (OVERALL, A**2) : 28.71
REMARK 3 OVERALL ANISOTROPIC B VALUE.
REMARK 3 B11 (A**2) : 0.88140
REMARK 3 B22 (A**2) : 4.72100
REMARK 3 B33 (A**2) : -5.60230
REMARK 3 B12 (A**2) : 0.00000
REMARK 3 B13 (A**2) : -1.37060
REMARK 3 B23 (A**2) : 0.00000
REMARK 3
REMARK 3 ESTIMATED COORDINATE ERROR.
REMARK 3 ESD FROM LUZZATI PLOT (A) : NULL
REMARK 3 DPI (BLOW EQ-10) BASED ON R VALUE (A) : 0.152
REMARK 3 DPI (BLOW EQ-9) BASED ON FREE R VALUE (A) : 0.135
REMARK 3 DPI (CRUICKSHANK) BASED ON R VALUE (A) : 0.147
REMARK 3 DPI (CRUICKSHANK) BASED ON FREE R VALUE (A) : 0.134
REMARK 3
REMARK 3 REFERENCES: BLOW, D. (2002) ACTA CRYST D58, 792-797
REMARK 3 CRUICKSHANK, D.W.J. (1999) ACTA CRYST D55, 583-601
REMARK 3
REMARK 3 CORRELATION COEFFICIENTS.
REMARK 3 CORRELATION COEFFICIENT FO-FC : 0.949
REMARK 3 CORRELATION COEFFICIENT FO-FC FREE : 0.927
REMARK 3
REMARK 3 NUMBER OF GEOMETRIC FUNCTION TERMS DEFINED : 15
REMARK 3 TERM COUNT WEIGHT FUNCTION.
REMARK 3 BOND LENGTHS : 2489 ; 2.000 ; HARMONIC
REMARK 3 BOND ANGLES : 3386 ; 2.000 ; HARMONIC
REMARK 3 TORSION ANGLES : 841 ; 2.000 ; SINUSOIDAL
REMARK 3 TRIGONAL CARBON PLANES : 53 ; 2.000 ; HARMONIC
REMARK 3 GENERAL PLANES : 403 ; 5.000 ; HARMONIC
REMARK 3 ISOTROPIC THERMAL FACTORS : 2489 ; 20.000 ; HARMONIC
REMARK 3 BAD NON-BONDED CONTACTS : NULL ; NULL ; NULL
REMARK 3 IMPROPER TORSIONS : NULL ; NULL ; NULL
REMARK 3 PSEUDOROTATION ANGLES : NULL ; NULL ; NULL
REMARK 3 CHIRAL IMPROPER TORSION : 295 ; 5.000 ; SEMIHARMONIC
REMARK 3 SUM OF OCCUPANCIES : NULL ; NULL ; NULL
REMARK 3 UTILITY DISTANCES : NULL ; NULL ; NULL
REMARK 3 UTILITY ANGLES : NULL ; NULL ; NULL
REMARK 3 UTILITY TORSION : NULL ; NULL ; NULL
REMARK 3 IDEAL-DIST CONTACT TERM : 2949 ; 4.000 ; SEMIHARMONIC
REMARK 3
REMARK 3 RMS DEVIATIONS FROM IDEAL VALUES.
REMARK 3 BOND LENGTHS (A) : 0.010
REMARK 3 BOND ANGLES (DEGREES) : 0.97
REMARK 3 PEPTIDE OMEGA TORSION ANGLES (DEGREES) : 3.29
REMARK 3 OTHER TORSION ANGLES (DEGREES) : 15.70
REMARK 3
REMARK 3 TLS DETAILS
REMARK 3 NUMBER OF TLS GROUPS : NULL
REMARK 3
REMARK 3 OTHER REFINEMENT REMARKS: NULL
REMARK 4
REMARK 4 6D20 COMPLIES WITH FORMAT V. 3.30, 13-JUL-11
REMARK 100
REMARK 100 THIS ENTRY HAS BEEN PROCESSED BY RCSB ON 13-APR-18.
REMARK 100 THE DEPOSITION ID IS D_1000233878.
REMARK 200
REMARK 200 EXPERIMENTAL DETAILS
REMARK 200 EXPERIMENT TYPE : X-RAY DIFFRACTION
REMARK 200 DATE OF DATA COLLECTION : 29-JAN-15
REMARK 200 TEMPERATURE (KELVIN) : 93
REMARK 200 PH : 8.0
REMARK 200 NUMBER OF CRYSTALS USED : 1
REMARK 200
REMARK 200 SYNCHROTRON (Y/N) : Y
REMARK 200 RADIATION SOURCE : CLSI
REMARK 200 BEAMLINE : 08ID-1
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 : NULL
REMARK 200 OPTICS : NULL
REMARK 200
REMARK 200 DETECTOR TYPE : CCD
REMARK 200 DETECTOR MANUFACTURER : RAYONIX MX-300
REMARK 200 INTENSITY-INTEGRATION SOFTWARE : HKL-2000
REMARK 200 DATA SCALING SOFTWARE : SCALEPACK
REMARK 200
REMARK 200 NUMBER OF UNIQUE REFLECTIONS : 23960
REMARK 200 RESOLUTION RANGE HIGH (A) : 1.940
REMARK 200 RESOLUTION RANGE LOW (A) : 50.000
REMARK 200 REJECTION CRITERIA (SIGMA(I)) : NULL
REMARK 200
REMARK 200 OVERALL.
REMARK 200 COMPLETENESS FOR RANGE (%) : 98.4
REMARK 200 DATA REDUNDANCY : 3.800
REMARK 200 R MERGE (I) : 0.11500
REMARK 200 R SYM (I) : NULL
REMARK 200 <I/SIGMA(I)> FOR THE DATA SET : 7.9000
REMARK 200
REMARK 200 IN THE HIGHEST RESOLUTION SHELL.
REMARK 200 HIGHEST RESOLUTION SHELL, RANGE HIGH (A) : 1.95
REMARK 200 HIGHEST RESOLUTION SHELL, RANGE LOW (A) : 2.02
REMARK 200 COMPLETENESS FOR SHELL (%) : 97.1
REMARK 200 DATA REDUNDANCY IN SHELL : 3.50
REMARK 200 R MERGE FOR SHELL (I) : 0.70800
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: NULL
REMARK 200 SOFTWARE USED: BUSTER
REMARK 200 STARTING MODEL: NULL
REMARK 200
REMARK 200 REMARK: NULL
REMARK 280
REMARK 280 CRYSTAL
REMARK 280 SOLVENT CONTENT, VS (%): 46.35
REMARK 280 MATTHEWS COEFFICIENT, VM (ANGSTROMS**3/DA): 2.29
REMARK 280
REMARK 280 CRYSTALLIZATION CONDITIONS: WELL VOLUME: 30.0 UL WELL INGREDIENTS:
REMARK 280 POLYMER: 10.0 %W/V (6.0 UL OF STOCK 50.0 %W/V) PEG 3350 BUFFER:
REMARK 280 16.0 %V/V (4.8 UL OF STOCK 100.0 %V/V) TACSIMATE (PH 8.00)
REMARK 280 ORGANIC (NON-VOLATILE): 10.0 %V/V (3.0 UL OF STOCK 100.0 %V/V)
REMARK 280 ETHYLENE GLYCOL ADDITIVE: 0.025 M (1.5 UL OF STOCK 0.5 M) TCEP
REMARK 280 HYDROCHLORIDE PLATE SETUP TEMPERATURE: 13 C PLATE INCUBATION
REMARK 280 TEMPERATURE: 21 C DROP VOLUME FROM WELL: 0.2 UL DROP PROTEIN
REMARK 280 VOLUME: 0.4 UL PROTEIN: 6.30 MG/ML (0.17 MM) COMPOUND1: 1.00 MM
REMARK 280 (TO AID CRYSTALLIZATION). COMPOUND23 (ALLOSTRIC INHIBITOR):
REMARK 280 1.3UL 50MM COMPOUND23 DMSO STOCK IN 133UL PROTEIN (0.50 MM),
REMARK 280 VAPOR DIFFUSION, HANGING DROP, TEMPERATURE 294K
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 56.97000
REMARK 290 SMTRY2 3 0.000000 1.000000 0.000000 22.90500
REMARK 290 SMTRY3 3 0.000000 0.000000 1.000000 0.00000
REMARK 290 SMTRY1 4 -1.000000 0.000000 0.000000 56.97000
REMARK 290 SMTRY2 4 0.000000 1.000000 0.000000 22.90500
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 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 375
REMARK 375 SPECIAL POSITION
REMARK 375 THE FOLLOWING ATOMS ARE FOUND TO BE WITHIN 0.15 ANGSTROMS
REMARK 375 OF A SYMMETRY RELATED ATOM AND ARE ASSUMED TO BE ON SPECIAL
REMARK 375 POSITIONS.
REMARK 375
REMARK 375 ATOM RES CSSEQI
REMARK 375 HOH A 902 LIES ON A SPECIAL POSITION.
REMARK 375 HOH A 943 LIES ON A SPECIAL POSITION.
REMARK 375 HOH A1082 LIES ON A SPECIAL POSITION.
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 477
REMARK 465 SER A 478
REMARK 465 THR A 479
REMARK 465 GLU A 480
REMARK 465 GLY A 481
REMARK 465 PRO A 494
REMARK 465 GLN A 495
REMARK 465 TYR A 496
REMARK 465 PHE A 497
REMARK 465 SER A 498
REMARK 465 ASP A 499
REMARK 465 LYS A 609
REMARK 465 LEU A 610
REMARK 465 LEU A 611
REMARK 465 ALA A 612
REMARK 465 GLY A 613
REMARK 465 GLY A 614
REMARK 465 GLU A 615
REMARK 465 ASP A 616
REMARK 465 VAL A 617
REMARK 465 ALA A 618
REMARK 465 PRO A 619
REMARK 465 GLY A 685
REMARK 465 ARG A 686
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 482 CG CD CE NZ
REMARK 470 GLN A 660 CG CD OE1 NE2
REMARK 470 ARG A 682 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 649 -20.54 81.74
REMARK 500 ASP A 650 46.28 -141.74
REMARK 500 VAL A 683 -75.65 -126.56
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 A1124 DISTANCE = 6.59 ANGSTROMS
REMARK 800
REMARK 800 SITE
REMARK 800 SITE_IDENTIFIER: AC1
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: binding site for residue FQD A 801
REMARK 800
REMARK 800 SITE_IDENTIFIER: AC2
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: binding site for residue FQG A 802
REMARK 900
REMARK 900 RELATED ENTRIES
REMARK 900 RELATED ID: 6D1Y RELATED DB: PDB
REMARK 900 RELATED ALLOSTERIC INHIBITOR
REMARK 900 RELATED ID: 6D1Z RELATED DB: PDB
REMARK 900 RELATED ALLOSTERIC INHIBITOR
DBREF 6D20 A 479 796 UNP P04629 NTRK1_HUMAN 381 698
SEQADV 6D20 GLY A 477 UNP P04629 EXPRESSION TAG
SEQADV 6D20 SER A 478 UNP P04629 EXPRESSION TAG
SEQRES 1 A 320 GLY SER THR GLU GLY LYS GLY SER GLY LEU GLN GLY HIS
SEQRES 2 A 320 ILE ILE GLU ASN PRO GLN TYR PHE SER ASP ALA CYS VAL
SEQRES 3 A 320 HIS HIS ILE LYS ARG ARG ASP ILE VAL LEU LYS TRP GLU
SEQRES 4 A 320 LEU GLY GLU GLY ALA PHE GLY LYS VAL PHE LEU ALA GLU
SEQRES 5 A 320 CYS HIS ASN LEU LEU PRO GLU GLN ASP LYS MET LEU VAL
SEQRES 6 A 320 ALA VAL LYS ALA LEU LYS GLU ALA SER GLU SER ALA ARG
SEQRES 7 A 320 GLN ASP PHE GLN ARG GLU ALA GLU LEU LEU THR MET LEU
SEQRES 8 A 320 GLN HIS GLN HIS ILE VAL ARG PHE PHE GLY VAL CYS THR
SEQRES 9 A 320 GLU GLY ARG PRO LEU LEU MET VAL PHE GLU TYR MET ARG
SEQRES 10 A 320 HIS GLY ASP LEU ASN ARG PHE LEU ARG SER HIS GLY PRO
SEQRES 11 A 320 ASP ALA LYS LEU LEU ALA GLY GLY GLU ASP VAL ALA PRO
SEQRES 12 A 320 GLY PRO LEU GLY LEU GLY GLN LEU LEU ALA VAL ALA SER
SEQRES 13 A 320 GLN VAL ALA ALA GLY MET VAL TYR LEU ALA GLY LEU HIS
SEQRES 14 A 320 PHE VAL HIS ARG ASP LEU ALA THR ARG ASN CYS LEU VAL
SEQRES 15 A 320 GLY GLN GLY LEU VAL VAL LYS ILE GLY ASP PHE GLY MET
SEQRES 16 A 320 SER ARG ASP ILE TYR SER THR ASP TYR TYR ARG VAL GLY
SEQRES 17 A 320 GLY ARG THR MET LEU PRO ILE ARG TRP MET PRO PRO GLU
SEQRES 18 A 320 SER ILE LEU TYR ARG LYS PHE THR THR GLU SER ASP VAL
SEQRES 19 A 320 TRP SER PHE GLY VAL VAL LEU TRP GLU ILE PHE THR TYR
SEQRES 20 A 320 GLY LYS GLN PRO TRP TYR GLN LEU SER ASN THR GLU ALA
SEQRES 21 A 320 ILE ASP CYS ILE THR GLN GLY ARG GLU LEU GLU ARG PRO
SEQRES 22 A 320 ARG ALA CYS PRO PRO GLU VAL TYR ALA ILE MET ARG GLY
SEQRES 23 A 320 CYS TRP GLN ARG GLU PRO GLN GLN ARG HIS SER ILE LYS
SEQRES 24 A 320 ASP VAL HIS ALA ARG LEU GLN ALA LEU ALA GLN ALA PRO
SEQRES 25 A 320 PRO VAL TYR LEU ASP VAL LEU GLY
HET FQD A 801 17
HET FQG A 802 59
HETNAM FQD 5-(4-FLUOROPHENYL)THIENO[2,3-D]PYRIMIDIN-4(3H)-ONE
HETNAM FQG 5-{[2,4-DICHLORO-5-(PYRIDIN-2-YL)BENZENE-1-
HETNAM 2 FQG CARBONYL]AMINO}-N-(2-HYDROXY-2-METHYLPROPYL)-1-PHENYL-
HETNAM 3 FQG 1H-PYRAZOLE-3-CARBOXAMIDE
FORMUL 2 FQD C12 H7 F N2 O S
FORMUL 3 FQG C26 H23 CL2 N5 O3
FORMUL 4 HOH *224(H2 O)
HELIX 1 AA1 SER A 484 ASN A 493 1 10
HELIX 2 AA2 LYS A 506 ARG A 508 5 3
HELIX 3 AA3 SER A 550 LEU A 567 1 18
HELIX 4 AA4 ASP A 596 HIS A 604 1 9
HELIX 5 AA5 GLY A 623 LEU A 644 1 22
HELIX 6 AA6 ALA A 652 ARG A 654 5 3
HELIX 7 AA7 MET A 671 TYR A 676 1 6
HELIX 8 AA8 SER A 677 TYR A 680 5 4
HELIX 9 AA9 PRO A 690 MET A 694 5 5
HELIX 10 AB1 PRO A 695 ARG A 702 1 8
HELIX 11 AB2 THR A 705 THR A 722 1 18
HELIX 12 AB3 SER A 732 GLY A 743 1 12
HELIX 13 AB4 PRO A 753 TRP A 764 1 12
HELIX 14 AB5 GLU A 767 ARG A 771 5 5
HELIX 15 AB6 SER A 773 ALA A 787 1 15
HELIX 16 AB7 LEU A 792 GLY A 796 5 5
SHEET 1 AA1 5 ILE A 510 GLY A 519 0
SHEET 2 AA1 5 GLY A 522 CYS A 529 -1 O GLY A 522 N GLY A 519
SHEET 3 AA1 5 MET A 539 LEU A 546 -1 O ALA A 545 N LYS A 523
SHEET 4 AA1 5 LEU A 585 GLU A 590 -1 O PHE A 589 N ALA A 542
SHEET 5 AA1 5 PHE A 575 CYS A 579 -1 N GLY A 577 O VAL A 588
SHEET 1 AA2 2 CYS A 656 GLY A 659 0
SHEET 2 AA2 2 VAL A 663 ILE A 666 -1 O LYS A 665 N LEU A 657
SHEET 1 AA3 2 TYR A 681 ARG A 682 0
SHEET 2 AA3 2 MET A 688 LEU A 689 -1 O LEU A 689 N TYR A 681
CISPEP 1 ARG A 583 PRO A 584 0 -2.90
SITE 1 AC1 8 LEU A 512 LYS A 513 TRP A 514 GLU A 515
SITE 2 AC1 8 PHE A 525 ALA A 545 LYS A 547 HOH A 999
SITE 1 AC2 15 SER A 484 GLY A 485 LEU A 486 LYS A 544
SITE 2 AC2 15 GLU A 560 LEU A 564 VAL A 573 PHE A 589
SITE 3 AC2 15 PHE A 646 HIS A 648 GLY A 667 ASP A 668
SITE 4 AC2 15 GLY A 670 ARG A 673 HOH A 918
CRYST1 113.940 45.810 79.490 90.00 127.04 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 0.008777 0.000000 0.006623 0.00000
SCALE2 0.000000 0.021829 0.000000 0.00000
SCALE3 0.000000 0.000000 0.015760 0.00000
(ATOM LINES ARE NOT SHOWN.)
END
