HEADER ANTITUMOR PROTEIN 16-DEC-16 5U9D
TITLE DISCOVERY OF A POTENT BTK INHIBITOR WITH A NOVEL BINDING MODE USING
TITLE 2 PARALLEL SELECTIONS WITH A DNA-ENCODED CHEMICAL LIBRARY
COMPND MOL_ID: 1;
COMPND 2 MOLECULE: TYROSINE-PROTEIN KINASE BTK;
COMPND 3 CHAIN: A;
COMPND 4 FRAGMENT: KINASE DOMAIN, UNP RESIDUES 423-693;
COMPND 5 SYNONYM: AGAMMAGLOBULINEMIA TYROSINE KINASE,ATK,B-CELL PROGENITOR
COMPND 6 KINASE,BPK,BRUTON TYROSINE KINASE;
COMPND 7 EC: 2.7.10.2;
COMPND 8 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: BTK, AGMX1, ATK, BPK;
SOURCE 6 EXPRESSION_SYSTEM: UNIDENTIFIED BACULOVIRUS;
SOURCE 7 EXPRESSION_SYSTEM_TAXID: 10469
KEYWDS BRUTONS TYROSINE KINASE, BTK, PROTEIN KINASE, DNA ENCODED LIBRARY,
KEYWDS 2 PROTEROS BIOSTRUCTURES GMBH, ANTITUMOR PROTEIN
EXPDTA X-RAY DIFFRACTION
AUTHOR J.W.CUOZZO,P.A.CENTRELLA,D.GIKUNJU,S.HABESHIAN,C.D.HUPP,A.D.KEEFE,
AUTHOR 2 E.SIGEL,H.H.SOUTTER,H.A.THOMSON,Y.ZHANG,M.A.CLARK
REVDAT 4 06-MAR-24 5U9D 1 REMARK
REVDAT 3 10-MAY-17 5U9D 1 JRNL
REVDAT 2 22-FEB-17 5U9D 1 JRNL
REVDAT 1 18-JAN-17 5U9D 0
JRNL AUTH J.W.CUOZZO,P.A.CENTRELLA,D.GIKUNJU,S.HABESHIAN,C.D.HUPP,
JRNL AUTH 2 A.D.KEEFE,E.A.SIGEL,H.H.SOUTTER,H.A.THOMSON,Y.ZHANG,
JRNL AUTH 3 M.A.CLARK
JRNL TITL DISCOVERY OF A POTENT BTK INHIBITOR WITH A NOVEL BINDING
JRNL TITL 2 MODE BY USING PARALLEL SELECTIONS WITH A DNA-ENCODED
JRNL TITL 3 CHEMICAL LIBRARY.
JRNL REF CHEMBIOCHEM V. 18 864 2017
JRNL REFN ESSN 1439-7633
JRNL PMID 28056160
JRNL DOI 10.1002/CBIC.201600573
REMARK 2
REMARK 2 RESOLUTION. 1.33 ANGSTROMS.
REMARK 3
REMARK 3 REFINEMENT.
REMARK 3 PROGRAM : REFMAC 5.8.0049
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) : 1.33
REMARK 3 RESOLUTION RANGE LOW (ANGSTROMS) : 58.85
REMARK 3 DATA CUTOFF (SIGMA(F)) : 0.000
REMARK 3 COMPLETENESS FOR RANGE (%) : 99.7
REMARK 3 NUMBER OF REFLECTIONS : 58769
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) : 0.151
REMARK 3 R VALUE (WORKING SET) : 0.148
REMARK 3 FREE R VALUE : 0.178
REMARK 3 FREE R VALUE TEST SET SIZE (%) : 10.000
REMARK 3 FREE R VALUE TEST SET COUNT : 6526
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) : 1.33
REMARK 3 BIN RESOLUTION RANGE LOW (A) : 1.37
REMARK 3 REFLECTION IN BIN (WORKING SET) : 4243
REMARK 3 BIN COMPLETENESS (WORKING+TEST) (%) : 98.31
REMARK 3 BIN R VALUE (WORKING SET) : 0.3780
REMARK 3 BIN FREE R VALUE SET COUNT : 455
REMARK 3 BIN FREE R VALUE : 0.4150
REMARK 3
REMARK 3 NUMBER OF NON-HYDROGEN ATOMS USED IN REFINEMENT.
REMARK 3 PROTEIN ATOMS : 2214
REMARK 3 NUCLEIC ACID ATOMS : 0
REMARK 3 HETEROGEN ATOMS : 62
REMARK 3 SOLVENT ATOMS : 338
REMARK 3
REMARK 3 B VALUES.
REMARK 3 FROM WILSON PLOT (A**2) : NULL
REMARK 3 MEAN B VALUE (OVERALL, A**2) : 16.33
REMARK 3 OVERALL ANISOTROPIC B VALUE.
REMARK 3 B11 (A**2) : 0.65000
REMARK 3 B22 (A**2) : -0.39000
REMARK 3 B33 (A**2) : -0.26000
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): 0.059
REMARK 3 ESU BASED ON FREE R VALUE (A): 0.054
REMARK 3 ESU BASED ON MAXIMUM LIKELIHOOD (A): 0.035
REMARK 3 ESU FOR B VALUES BASED ON MAXIMUM LIKELIHOOD (A**2): 1.957
REMARK 3
REMARK 3 CORRELATION COEFFICIENTS.
REMARK 3 CORRELATION COEFFICIENT FO-FC : 0.974
REMARK 3 CORRELATION COEFFICIENT FO-FC FREE : 0.966
REMARK 3
REMARK 3 RMS DEVIATIONS FROM IDEAL VALUES COUNT RMS WEIGHT
REMARK 3 BOND LENGTHS REFINED ATOMS (A): 2558 ; 0.008 ; 0.019
REMARK 3 BOND LENGTHS OTHERS (A): 2355 ; 0.001 ; 0.020
REMARK 3 BOND ANGLES REFINED ATOMS (DEGREES): 3480 ; 1.410 ; 1.979
REMARK 3 BOND ANGLES OTHERS (DEGREES): 5449 ; 2.942 ; 3.000
REMARK 3 TORSION ANGLES, PERIOD 1 (DEGREES): 320 ; 6.333 ; 5.000
REMARK 3 TORSION ANGLES, PERIOD 2 (DEGREES): 117 ;31.696 ;23.846
REMARK 3 TORSION ANGLES, PERIOD 3 (DEGREES): 450 ;12.437 ;15.000
REMARK 3 TORSION ANGLES, PERIOD 4 (DEGREES): 14 ;12.966 ;15.000
REMARK 3 CHIRAL-CENTER RESTRAINTS (A**3): 352 ; 0.093 ; 0.200
REMARK 3 GENERAL PLANES REFINED ATOMS (A): 2977 ; 0.007 ; 0.020
REMARK 3 GENERAL PLANES OTHERS (A): 612 ; 0.006 ; 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): 4913 ; 1.537 ; 3.000
REMARK 3 SPHERICITY; FREE ATOMS (A**2): 74 ;28.923 ; 5.000
REMARK 3 SPHERICITY; BONDED ATOMS (A**2): 5096 ; 7.325 ; 5.000
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 : 1.20
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 U VALUES : REFINED INDIVIDUALLY
REMARK 4
REMARK 4 5U9D COMPLIES WITH FORMAT V. 3.30, 13-JUL-11
REMARK 100
REMARK 100 THIS ENTRY HAS BEEN PROCESSED BY RCSB ON 22-DEC-16.
REMARK 100 THE DEPOSITION ID IS D_1000225280.
REMARK 200
REMARK 200 EXPERIMENTAL DETAILS
REMARK 200 EXPERIMENT TYPE : X-RAY DIFFRACTION
REMARK 200 DATE OF DATA COLLECTION : 01-AUG-16
REMARK 200 TEMPERATURE (KELVIN) : 100.000
REMARK 200 PH : 6.0-6.7
REMARK 200 NUMBER OF CRYSTALS USED : 1
REMARK 200
REMARK 200 SYNCHROTRON (Y/N) : Y
REMARK 200 RADIATION SOURCE : SLS
REMARK 200 BEAMLINE : X06DA
REMARK 200 X-RAY GENERATOR MODEL : NULL
REMARK 200 MONOCHROMATIC OR LAUE (M/L) : M
REMARK 200 WAVELENGTH OR RANGE (A) : 1.00000
REMARK 200 MONOCHROMATOR : NULL
REMARK 200 OPTICS : NULL
REMARK 200
REMARK 200 DETECTOR TYPE : PIXEL
REMARK 200 DETECTOR MANUFACTURER : DECTRIS PILATUS 2M
REMARK 200 INTENSITY-INTEGRATION SOFTWARE : XDS
REMARK 200 DATA SCALING SOFTWARE : XSCALE
REMARK 200
REMARK 200 NUMBER OF UNIQUE REFLECTIONS : 65295
REMARK 200 RESOLUTION RANGE HIGH (A) : 1.330
REMARK 200 RESOLUTION RANGE LOW (A) : 58.850
REMARK 200 REJECTION CRITERIA (SIGMA(I)) : NULL
REMARK 200
REMARK 200 OVERALL.
REMARK 200 COMPLETENESS FOR RANGE (%) : 99.7
REMARK 200 DATA REDUNDANCY : 7.900
REMARK 200 R MERGE (I) : NULL
REMARK 200 R SYM (I) : NULL
REMARK 200 <I/SIGMA(I)> FOR THE DATA SET : 23.8000
REMARK 200
REMARK 200 IN THE HIGHEST RESOLUTION SHELL.
REMARK 200 HIGHEST RESOLUTION SHELL, RANGE HIGH (A) : 1.33
REMARK 200 HIGHEST RESOLUTION SHELL, RANGE LOW (A) : 1.54
REMARK 200 COMPLETENESS FOR SHELL (%) : 99.5
REMARK 200 DATA REDUNDANCY IN SHELL : 7.70
REMARK 200 R MERGE FOR SHELL (I) : 0.43400
REMARK 200 R SYM FOR SHELL (I) : NULL
REMARK 200 <I/SIGMA(I)> FOR SHELL : 5.030
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: NONE
REMARK 200
REMARK 200 REMARK: NULL
REMARK 280
REMARK 280 CRYSTAL
REMARK 280 SOLVENT CONTENT, VS (%): 46.50
REMARK 280 MATTHEWS COEFFICIENT, VM (ANGSTROMS**3/DA): 2.30
REMARK 280
REMARK 280 CRYSTALLIZATION CONDITIONS: POLYETHYLENE GLYCOLS (PEG3350 /
REMARK 280 PEG5000MME), (NH4)2SO4 AND MES BUFFER AT PH6.0-6.7, VAPOR
REMARK 280 DIFFUSION, SITTING DROP, TEMPERATURE 298K
REMARK 290
REMARK 290 CRYSTALLOGRAPHIC SYMMETRY
REMARK 290 SYMMETRY OPERATORS FOR SPACE GROUP: P 21 21 2
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 35.77650
REMARK 290 SMTRY2 3 0.000000 1.000000 0.000000 51.74150
REMARK 290 SMTRY3 3 0.000000 0.000000 -1.000000 0.00000
REMARK 290 SMTRY1 4 1.000000 0.000000 0.000000 35.77650
REMARK 290 SMTRY2 4 0.000000 -1.000000 0.000000 51.74150
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 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 LYS A 406 CD CE NZ
REMARK 480 GLN A 412 CG CD OE1 NE2
REMARK 480 GLU A 434 CD OE1 OE2
REMARK 480 LYS A 466 CE NZ
REMARK 480 GLN A 467 CG CD OE1 NE2
REMARK 480 GLU A 550 CG CD OE1 OE2
REMARK 480 SER A 554 OG
REMARK 480 VAL A 555 CG1 CG2
REMARK 480 LYS A 558 CE NZ
REMARK 480 LYS A 637 NZ
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 GLN A 424 -46.83 -135.05
REMARK 500 ARG A 520 -10.04 78.01
REMARK 500 ASP A 521 47.78 -152.68
REMARK 500 TYR A 571 31.55 -148.84
REMARK 500
REMARK 500 REMARK: NULL
REMARK 615
REMARK 615 ZERO OCCUPANCY ATOM
REMARK 615 THE FOLLOWING RESIDUES HAVE ATOMS MODELED WITH ZERO
REMARK 615 OCCUPANCY. THE LOCATION AND PROPERTIES OF THESE ATOMS
REMARK 615 MAY NOT BE RELIABLE. (M=MODEL NUMBER; RES=RESIDUE NAME;
REMARK 615 C=CHAIN IDENTIFIER; SSEQ=SEQUENCE NUMBER; I=INSERTION CODE):
REMARK 615 M RES C SSEQI
REMARK 615 PEG A 706
REMARK 800
REMARK 800 SITE
REMARK 800 SITE_IDENTIFIER: AC1
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: binding site for residue 83P A 701
REMARK 800
REMARK 800 SITE_IDENTIFIER: AC2
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: binding site for residue EDO A 702
REMARK 800
REMARK 800 SITE_IDENTIFIER: AC3
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: binding site for residue EDO A 703
REMARK 800
REMARK 800 SITE_IDENTIFIER: AC4
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: binding site for residue EDO A 704
REMARK 800
REMARK 800 SITE_IDENTIFIER: AC5
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: binding site for residue PEG A 705
REMARK 800
REMARK 800 SITE_IDENTIFIER: AC6
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: binding site for residue PEG A 706
DBREF 5U9D A 389 659 UNP Q06187 BTK_HUMAN 423 693
SEQRES 1 A 271 GLY LEU GLY TYR GLY SER TRP GLU ILE ASP PRO LYS ASP
SEQRES 2 A 271 LEU THR PHE LEU LYS GLU LEU GLY THR GLY GLN PHE GLY
SEQRES 3 A 271 VAL VAL LYS TYR GLY LYS TRP ARG GLY GLN TYR ASP VAL
SEQRES 4 A 271 ALA ILE LYS MET ILE LYS GLU GLY SER MET SER GLU ASP
SEQRES 5 A 271 GLU PHE ILE GLU GLU ALA LYS VAL MET MET ASN LEU SER
SEQRES 6 A 271 HIS GLU LYS LEU VAL GLN LEU TYR GLY VAL CYS THR LYS
SEQRES 7 A 271 GLN ARG PRO ILE PHE ILE ILE THR GLU TYR MET ALA ASN
SEQRES 8 A 271 GLY CYS LEU LEU ASN TYR LEU ARG GLU MET ARG HIS ARG
SEQRES 9 A 271 PHE GLN THR GLN GLN LEU LEU GLU MET CYS LYS ASP VAL
SEQRES 10 A 271 CYS GLU ALA MET GLU TYR LEU GLU SER LYS GLN PHE LEU
SEQRES 11 A 271 HIS ARG ASP LEU ALA ALA ARG ASN CYS LEU VAL ASN ASP
SEQRES 12 A 271 GLN GLY VAL VAL LYS VAL SER ASP PHE GLY LEU SER ARG
SEQRES 13 A 271 TYR VAL LEU ASP ASP GLU TYR THR SER SER VAL GLY SER
SEQRES 14 A 271 LYS PHE PRO VAL ARG TRP SER PRO PRO GLU VAL LEU MET
SEQRES 15 A 271 TYR SER LYS PHE SER SER LYS SER ASP ILE TRP ALA PHE
SEQRES 16 A 271 GLY VAL LEU MET TRP GLU ILE TYR SER LEU GLY LYS MET
SEQRES 17 A 271 PRO TYR GLU ARG PHE THR ASN SER GLU THR ALA GLU HIS
SEQRES 18 A 271 ILE ALA GLN GLY LEU ARG LEU TYR ARG PRO HIS LEU ALA
SEQRES 19 A 271 SER GLU LYS VAL TYR THR ILE MET TYR SER CYS TRP HIS
SEQRES 20 A 271 GLU LYS ALA ASP GLU ARG PRO THR PHE LYS ILE LEU LEU
SEQRES 21 A 271 SER ASN ILE LEU ASP VAL MET ASP GLU GLU SER
HET 83P A 701 36
HET EDO A 702 4
HET EDO A 703 4
HET EDO A 704 4
HET PEG A 705 7
HET PEG A 706 7
HETNAM 83P (R)-N-METHYL-2-(3-((QUINOXALIN-6-YLAMINO)METHYL)FURAN-
HETNAM 2 83P 2-CARBONYL)-2,3,4,9-TETRAHYDRO-1H-PYRIDO[3,4-B]INDOLE-
HETNAM 3 83P 3-CARBOXAMIDE
HETNAM EDO 1,2-ETHANEDIOL
HETNAM PEG DI(HYDROXYETHYL)ETHER
HETSYN 83P (3R)-N-METHYL-2-(3-{[(QUINOXALIN-6-YL)
HETSYN 2 83P AMINO]METHYL}FURAN-2-CARBONYL)-2,3,4,9-TETRAHYDRO-1H-
HETSYN 3 83P BETA-CARBOLINE-3-CARBOXAMIDE
HETSYN EDO ETHYLENE GLYCOL
FORMUL 2 83P C27 H24 N6 O3
FORMUL 3 EDO 3(C2 H6 O2)
FORMUL 6 PEG 2(C4 H10 O3)
FORMUL 8 HOH *338(H2 O)
HELIX 1 AA1 ASP A 398 LYS A 400 5 3
HELIX 2 AA2 SER A 438 MET A 450 1 13
HELIX 3 AA3 LEU A 482 GLU A 488 1 7
HELIX 4 AA4 MET A 489 ARG A 492 5 4
HELIX 5 AA5 GLN A 494 LYS A 515 1 22
HELIX 6 AA6 ALA A 523 ARG A 525 5 3
HELIX 7 AA7 GLY A 541 VAL A 546 5 6
HELIX 8 AA8 ASP A 548 SER A 553 1 6
HELIX 9 AA9 PRO A 560 SER A 564 5 5
HELIX 10 AB1 PRO A 565 SER A 572 1 8
HELIX 11 AB2 SER A 575 SER A 592 1 18
HELIX 12 AB3 THR A 602 GLN A 612 1 11
HELIX 13 AB4 SER A 623 CYS A 633 1 11
HELIX 14 AB5 LYS A 637 ARG A 641 5 5
HELIX 15 AB6 THR A 643 SER A 659 1 17
SHEET 1 AA1 5 LEU A 402 GLY A 411 0
SHEET 2 AA1 5 GLY A 414 TRP A 421 -1 O TYR A 418 N LYS A 406
SHEET 3 AA1 5 TYR A 425 ILE A 432 -1 O MET A 431 N VAL A 415
SHEET 4 AA1 5 PHE A 471 THR A 474 -1 O ILE A 472 N LYS A 430
SHEET 5 AA1 5 LEU A 460 CYS A 464 -1 N TYR A 461 O ILE A 473
SHEET 1 AA2 3 GLY A 480 CYS A 481 0
SHEET 2 AA2 3 CYS A 527 VAL A 529 -1 O VAL A 529 N GLY A 480
SHEET 3 AA2 3 VAL A 535 VAL A 537 -1 O LYS A 536 N LEU A 528
CISPEP 1 ARG A 468 PRO A 469 0 -0.18
SITE 1 AC1 20 LEU A 408 GLY A 409 THR A 410 GLY A 411
SITE 2 AC1 20 GLN A 412 PHE A 413 GLY A 414 VAL A 416
SITE 3 AC1 20 ALA A 428 LYS A 430 MET A 431 ILE A 472
SITE 4 AC1 20 GLU A 475 MET A 477 LEU A 528 ASP A 539
SITE 5 AC1 20 HOH A 899 HOH A 908 HOH A 958 HOH A1033
SITE 1 AC2 10 LYS A 400 TYR A 571 LYS A 573 ARG A 618
SITE 2 AC2 10 HIS A 620 LEU A 621 ALA A 622 SER A 623
SITE 3 AC2 10 HOH A 803 HOH A 876
SITE 1 AC3 6 TYR A 598 GLU A 599 ARG A 600 HOH A 830
SITE 2 AC3 6 HOH A 859 HOH A 870
SITE 1 AC4 3 PHE A 404 GLU A 407 LYS A 417
SITE 1 AC5 2 TRP A 421 TYR A 461
SITE 1 AC6 5 LYS A 420 GLN A 424 TYR A 425 ASP A 426
SITE 2 AC6 5 HOH A 894
CRYST1 71.553 103.483 37.839 90.00 90.00 90.00 P 21 21 2 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 0.013976 0.000000 0.000000 0.00000
SCALE2 0.000000 0.009663 0.000000 0.00000
SCALE3 0.000000 0.000000 0.026428 0.00000
(ATOM LINES ARE NOT SHOWN.)
END
