HEADER TRANSFERASE/TRANSFERASE INHIBITOR 06-MAY-16 5JRS
TITLE CRYSTAL STRUCTURE OF BRUTON AGAMMAGLOBULINEMIA TYROSINE KINASE
TITLE 2 COMPLEXED WITH 4-[2-FLUORO-3-(4-OXO -3,4-DIHYDROQUINAZOLIN-3-YL)
TITLE 3 PHENYL]-7-(2-HYDROXYPROPAN-2-Y L)-9H-CARBAZOLE-1-CARBOXAMIDE
COMPND MOL_ID: 1;
COMPND 2 MOLECULE: TYROSINE-PROTEIN KINASE BTK;
COMPND 3 CHAIN: A, B;
COMPND 4 FRAGMENT: KINASE DOMAIN (UNP RESIDUES 396-659;
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: SPODOPTERA FRUGIPERDA;
SOURCE 7 EXPRESSION_SYSTEM_COMMON: FALL ARMYWORM;
SOURCE 8 EXPRESSION_SYSTEM_TAXID: 7108;
SOURCE 9 EXPRESSION_SYSTEM_CELL_LINE: SF9;
SOURCE 10 EXPRESSION_SYSTEM_VECTOR_TYPE: BACULOVIRUS
KEYWDS KINASE, BTK, PROTEIN INHIBITOR COMPLEX, TRANSFERASE-TRANSFERASE
KEYWDS 2 INHIBITOR COMPLEX
EXPDTA X-RAY DIFFRACTION
AUTHOR J.K.MUCKELBAUER
REVDAT 3 06-MAR-24 5JRS 1 JRNL REMARK
REVDAT 2 21-SEP-16 5JRS 1 JRNL
REVDAT 1 31-AUG-16 5JRS 0
JRNL AUTH G.V.DE LUCCA,Q.SHI,Q.LIU,D.G.BATT,M.BEAUDOIN BERTRAND,
JRNL AUTH 2 R.RAMPULLA,A.MATHUR,L.DISCENZA,C.D'ARIENZO,J.DAI,
JRNL AUTH 3 M.OBERMEIER,R.VICKERY,Y.ZHANG,Z.YANG,P.MARATHE,A.J.TEBBEN,
JRNL AUTH 4 J.K.MUCKELBAUER,C.J.CHANG,H.ZHANG,K.GILLOOLY,T.TAYLOR,
JRNL AUTH 5 M.A.PATTOLI,S.SKALA,D.W.KUKRAL,K.W.MCINTYRE,L.SALTER-CID,
JRNL AUTH 6 A.FURA,J.R.BURKE,J.C.BARRISH,P.H.CARTER,J.A.TINO
JRNL TITL SMALL MOLECULE REVERSIBLE INHIBITORS OF BRUTON'S TYROSINE
JRNL TITL 2 KINASE (BTK): STRUCTURE-ACTIVITY RELATIONSHIPS LEADING TO
JRNL TITL 3 THE IDENTIFICATION OF
JRNL TITL 4 7-(2-HYDROXYPROPAN-2-YL)-4-[2-METHYL-3-(4-OXO-3,
JRNL TITL 5 4-DIHYDROQUINAZOLIN-3-YL)PHENYL]-9H-CARBAZOLE-1-CARBOXAMIDE
JRNL TITL 6 (BMS-935177).
JRNL REF J.MED.CHEM. V. 59 7915 2016
JRNL REFN ISSN 0022-2623
JRNL PMID 27531604
JRNL DOI 10.1021/ACS.JMEDCHEM.6B00722
REMARK 2
REMARK 2 RESOLUTION. 1.97 ANGSTROMS.
REMARK 3
REMARK 3 REFINEMENT.
REMARK 3 PROGRAM : BUSTER-TNT 2.11.7
REMARK 3 AUTHORS : BRICOGNE,BLANC,BRANDL,FLENSBURG,KELLER,
REMARK 3 : PACIOREK,ROVERSI,SMART,VONRHEIN,WOMACK,
REMARK 3 : MATTHEWS,TEN EYCK,TRONRUD
REMARK 3
REMARK 3 DATA USED IN REFINEMENT.
REMARK 3 RESOLUTION RANGE HIGH (ANGSTROMS) : 1.97
REMARK 3 RESOLUTION RANGE LOW (ANGSTROMS) : 39.20
REMARK 3 DATA CUTOFF (SIGMA(F)) : 0.000
REMARK 3 COMPLETENESS FOR RANGE (%) : 99.1
REMARK 3 NUMBER OF REFLECTIONS : 39665
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) : 0.203
REMARK 3 R VALUE (WORKING SET) : 0.202
REMARK 3 FREE R VALUE : 0.226
REMARK 3 FREE R VALUE TEST SET SIZE (%) : 5.020
REMARK 3 FREE R VALUE TEST SET COUNT : 1993
REMARK 3 ESTIMATED ERROR OF FREE R VALUE : 0.000
REMARK 3
REMARK 3 FIT IN THE HIGHEST RESOLUTION BIN.
REMARK 3 TOTAL NUMBER OF BINS USED : 20
REMARK 3 BIN RESOLUTION RANGE HIGH (ANGSTROMS) : 1.97
REMARK 3 BIN RESOLUTION RANGE LOW (ANGSTROMS) : 2.02
REMARK 3 BIN COMPLETENESS (WORKING+TEST) (%) : 96.04
REMARK 3 REFLECTIONS IN BIN (WORKING + TEST SET) : 2777
REMARK 3 BIN R VALUE (WORKING + TEST SET) : NULL
REMARK 3 REFLECTIONS IN BIN (WORKING SET) : 2600
REMARK 3 BIN R VALUE (WORKING SET) : 0.2150
REMARK 3 BIN FREE R VALUE : 0.2400
REMARK 3 BIN FREE R VALUE TEST SET SIZE (%) : 6.37
REMARK 3 BIN FREE R VALUE TEST SET COUNT : 177
REMARK 3 ESTIMATED ERROR OF BIN FREE R VALUE : NULL
REMARK 3
REMARK 3 NUMBER OF NON-HYDROGEN ATOMS USED IN REFINEMENT.
REMARK 3 PROTEIN ATOMS : 3898
REMARK 3 NUCLEIC ACID ATOMS : 0
REMARK 3 HETEROGEN ATOMS : 76
REMARK 3 SOLVENT ATOMS : 167
REMARK 3
REMARK 3 B VALUES.
REMARK 3 FROM WILSON PLOT (A**2) : 30.40
REMARK 3 MEAN B VALUE (OVERALL, A**2) : 32.57
REMARK 3 OVERALL ANISOTROPIC B VALUE.
REMARK 3 B11 (A**2) : -6.65000
REMARK 3 B22 (A**2) : 2.36720
REMARK 3 B33 (A**2) : 4.28280
REMARK 3 B12 (A**2) : 0.00000
REMARK 3 B13 (A**2) : 2.48850
REMARK 3 B23 (A**2) : 0.00000
REMARK 3
REMARK 3 ESTIMATED COORDINATE ERROR.
REMARK 3 ESD FROM LUZZATI PLOT (A) : 0.260
REMARK 3 DPI (BLOW EQ-10) BASED ON R VALUE (A) : 0.167
REMARK 3 DPI (BLOW EQ-9) BASED ON FREE R VALUE (A) : 0.142
REMARK 3 DPI (CRUICKSHANK) BASED ON R VALUE (A) : 0.286
REMARK 3 DPI (CRUICKSHANK) BASED ON FREE R VALUE (A) : 0.144
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 : 0.928
REMARK 3 CORRELATION COEFFICIENT FO-FC FREE : 0.916
REMARK 3
REMARK 3 NUMBER OF GEOMETRIC FUNCTION TERMS DEFINED : 15
REMARK 3 TERM COUNT WEIGHT FUNCTION.
REMARK 3 BOND LENGTHS : 7844 ; 2.000 ; HARMONIC
REMARK 3 BOND ANGLES : 14110 ; 2.000 ; HARMONIC
REMARK 3 TORSION ANGLES : 1674 ; 2.000 ; SINUSOIDAL
REMARK 3 TRIGONAL CARBON PLANES : 78 ; 2.000 ; HARMONIC
REMARK 3 GENERAL PLANES : 1255 ; 5.000 ; HARMONIC
REMARK 3 ISOTROPIC THERMAL FACTORS : 7844 ; 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 : 514 ; 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 : 8571 ; 4.000 ; SEMIHARMONIC
REMARK 3
REMARK 3 RMS DEVIATIONS FROM IDEAL VALUES.
REMARK 3 BOND LENGTHS (A) : 0.010
REMARK 3 BOND ANGLES (DEGREES) : 1.04
REMARK 3 PEPTIDE OMEGA TORSION ANGLES (DEGREES) : 3.73
REMARK 3 OTHER TORSION ANGLES (DEGREES) : 14.33
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 5JRS COMPLIES WITH FORMAT V. 3.30, 13-JUL-11
REMARK 100
REMARK 100 THIS ENTRY HAS BEEN PROCESSED BY RCSB ON 09-MAY-16.
REMARK 100 THE DEPOSITION ID IS D_1000221130.
REMARK 200
REMARK 200 EXPERIMENTAL DETAILS
REMARK 200 EXPERIMENT TYPE : X-RAY DIFFRACTION
REMARK 200 DATE OF DATA COLLECTION : 13-APR-11
REMARK 200 TEMPERATURE (KELVIN) : 100.0
REMARK 200 PH : 8.5
REMARK 200 NUMBER OF CRYSTALS USED : 1
REMARK 200
REMARK 200 SYNCHROTRON (Y/N) : Y
REMARK 200 RADIATION SOURCE : APS
REMARK 200 BEAMLINE : 17-ID
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 : PIXEL
REMARK 200 DETECTOR MANUFACTURER : DECTRIS PILATUS 6M
REMARK 200 INTENSITY-INTEGRATION SOFTWARE : XDS
REMARK 200 DATA SCALING SOFTWARE : SCALA 3.3.16
REMARK 200
REMARK 200 NUMBER OF UNIQUE REFLECTIONS : 39744
REMARK 200 RESOLUTION RANGE HIGH (A) : 1.970
REMARK 200 RESOLUTION RANGE LOW (A) : 49.060
REMARK 200 REJECTION CRITERIA (SIGMA(I)) : 0.000
REMARK 200
REMARK 200 OVERALL.
REMARK 200 COMPLETENESS FOR RANGE (%) : 99.2
REMARK 200 DATA REDUNDANCY : 3.200
REMARK 200 R MERGE (I) : 0.06200
REMARK 200 R SYM (I) : NULL
REMARK 200 <I/SIGMA(I)> FOR THE DATA SET : 10.8000
REMARK 200
REMARK 200 IN THE HIGHEST RESOLUTION SHELL.
REMARK 200 HIGHEST RESOLUTION SHELL, RANGE HIGH (A) : 1.97
REMARK 200 HIGHEST RESOLUTION SHELL, RANGE LOW (A) : 2.08
REMARK 200 COMPLETENESS FOR SHELL (%) : 97.9
REMARK 200 DATA REDUNDANCY IN SHELL : 2.80
REMARK 200 R MERGE FOR SHELL (I) : 0.43300
REMARK 200 R SYM FOR SHELL (I) : NULL
REMARK 200 <I/SIGMA(I)> FOR SHELL : 26.10
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: NULL
REMARK 200
REMARK 200 REMARK: NULL
REMARK 280
REMARK 280 CRYSTAL
REMARK 280 SOLVENT CONTENT, VS (%): 45.79
REMARK 280 MATTHEWS COEFFICIENT, VM (ANGSTROMS**3/DA): 2.27
REMARK 280
REMARK 280 CRYSTALLIZATION CONDITIONS: PEG 5000, PEG 8000, PH 8.5, VAPOR
REMARK 280 DIFFUSION, TEMPERATURE 298K
REMARK 290
REMARK 290 CRYSTALLOGRAPHIC SYMMETRY
REMARK 290 SYMMETRY OPERATORS FOR SPACE GROUP: P 1 21 1
REMARK 290
REMARK 290 SYMOP SYMMETRY
REMARK 290 NNNMMM OPERATOR
REMARK 290 1555 X,Y,Z
REMARK 290 2555 -X,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 22.74000
REMARK 290 SMTRY3 2 0.000000 0.000000 -1.000000 0.00000
REMARK 290
REMARK 290 REMARK: NULL
REMARK 300
REMARK 300 BIOMOLECULE: 1, 2, 3
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: DIMERIC
REMARK 350 APPLY THE FOLLOWING TO CHAINS: A, B
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 350
REMARK 350 BIOMOLECULE: 2
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 350
REMARK 350 BIOMOLECULE: 3
REMARK 350 SOFTWARE DETERMINED QUATERNARY STRUCTURE: MONOMERIC
REMARK 350 SOFTWARE USED: PISA
REMARK 350 APPLY THE FOLLOWING TO CHAINS: B
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 393
REMARK 465 HIS A 394
REMARK 465 MET A 489
REMARK 465 ARG A 490
REMARK 465 HIS A 491
REMARK 465 ARG A 492
REMARK 465 GLU A 657
REMARK 465 GLU A 658
REMARK 465 SER A 659
REMARK 465 GLY B 393
REMARK 465 HIS B 394
REMARK 465 GLU B 434
REMARK 465 GLY B 435
REMARK 465 LYS B 466
REMARK 465 GLN B 467
REMARK 465 ARG B 468
REMARK 465 PRO B 469
REMARK 465 MET B 489
REMARK 465 ARG B 490
REMARK 465 HIS B 491
REMARK 465 ARG B 492
REMARK 465 LEU B 547
REMARK 465 ASP B 548
REMARK 465 ASP B 549
REMARK 465 GLU B 550
REMARK 465 TYR B 551
REMARK 465 THR B 552
REMARK 465 SER B 553
REMARK 465 SER B 554
REMARK 465 VAL B 555
REMARK 465 GLY B 556
REMARK 465 SER B 557
REMARK 465 ASP B 656
REMARK 465 GLU B 657
REMARK 465 GLU B 658
REMARK 465 SER B 659
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 LEU A 405 CG CD1 CD2
REMARK 470 GLN A 412 CG CD OE1 NE2
REMARK 470 GLN A 424 CG CD OE1 NE2
REMARK 470 TYR A 425 CG CD1 CD2 CE1 CE2 CZ OH
REMARK 470 LYS A 466 CD CE NZ
REMARK 470 ARG A 468 CG CD NE CZ NH1 NH2
REMARK 470 GLU A 488 CG CD OE1 OE2
REMARK 470 GLN A 494 CG CD OE1 NE2
REMARK 470 LYS A 515 CE NZ
REMARK 470 ARG A 520 CG CD NE CZ NH1 NH2
REMARK 470 ARG A 544 CG CD NE CZ NH1 NH2
REMARK 470 ASP A 549 CG OD1 OD2
REMARK 470 GLU A 550 CG CD OE1 OE2
REMARK 470 VAL A 555 CG1 CG2
REMARK 470 GLU A 636 CG CD OE1 OE2
REMARK 470 ASP A 639 CG OD1 OD2
REMARK 470 ASP A 656 CG OD1 OD2
REMARK 470 LYS B 400 CG CD CE NZ
REMARK 470 LEU B 405 CG CD1 CD2
REMARK 470 LYS B 406 CG CD CE NZ
REMARK 470 GLN B 412 CG CD OE1 NE2
REMARK 470 GLN B 424 CG CD OE1 NE2
REMARK 470 ILE B 432 CG1 CG2 CD1
REMARK 470 LYS B 433 CG CD CE NZ
REMARK 470 SER B 438 OG
REMARK 470 GLU B 439 CG CD OE1 OE2
REMARK 470 GLU B 441 CG CD OE1 OE2
REMARK 470 GLU B 444 CG CD OE1 OE2
REMARK 470 GLU B 445 CG CD OE1 OE2
REMARK 470 LYS B 447 CG CD CE NZ
REMARK 470 MET B 450 CG SD CE
REMARK 470 ILE B 470 CG1 CG2 CD1
REMARK 470 GLU B 488 CG CD OE1 OE2
REMARK 470 GLN B 494 CG CD OE1 NE2
REMARK 470 THR B 495 OG1 CG2
REMARK 470 GLN B 496 CG CD OE1 NE2
REMARK 470 GLU B 500 CG CD OE1 OE2
REMARK 470 LYS B 515 CE NZ
REMARK 470 ARG B 520 CG CD NE CZ NH1 NH2
REMARK 470 GLN B 532 CG CD OE1 NE2
REMARK 470 ARG B 544 CG CD NE CZ NH1 NH2
REMARK 470 VAL B 546 CG1 CG2
REMARK 470 GLU B 608 CG CD OE1 OE2
REMARK 470 GLN B 612 CG CD OE1 NE2
REMARK 470 GLU B 636 CG CD OE1 OE2
REMARK 470 LYS B 637 CD CE NZ
REMARK 470 ASP B 639 OD1 OD2
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 405 -147.55 -97.14
REMARK 500 LYS A 406 153.10 -44.99
REMARK 500 ARG A 520 -14.06 84.33
REMARK 500 ASP A 521 47.78 -150.47
REMARK 500 LEU B 405 -145.37 -98.36
REMARK 500 LYS B 406 137.39 -38.20
REMARK 500 GLN B 424 -36.51 -130.67
REMARK 500 ARG B 520 -12.35 82.87
REMARK 500 ASP B 521 48.23 -152.18
REMARK 500 PRO B 560 0.13 -66.14
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 6MV A 4000
REMARK 800
REMARK 800 SITE_IDENTIFIER: AC2
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: binding site for residue 6MV B 4000
DBREF 5JRS A 396 659 UNP Q06187 BTK_HUMAN 396 659
DBREF 5JRS B 396 659 UNP Q06187 BTK_HUMAN 396 659
SEQADV 5JRS GLY A 393 UNP Q06187 EXPRESSION TAG
SEQADV 5JRS HIS A 394 UNP Q06187 EXPRESSION TAG
SEQADV 5JRS MET A 395 UNP Q06187 EXPRESSION TAG
SEQADV 5JRS GLY B 393 UNP Q06187 EXPRESSION TAG
SEQADV 5JRS HIS B 394 UNP Q06187 EXPRESSION TAG
SEQADV 5JRS MET B 395 UNP Q06187 EXPRESSION TAG
SEQRES 1 A 267 GLY HIS MET GLU ILE ASP PRO LYS ASP LEU THR PHE LEU
SEQRES 2 A 267 LYS GLU LEU GLY THR GLY GLN PHE GLY VAL VAL LYS TYR
SEQRES 3 A 267 GLY LYS TRP ARG GLY GLN TYR ASP VAL ALA ILE LYS MET
SEQRES 4 A 267 ILE LYS GLU GLY SER MET SER GLU ASP GLU PHE ILE GLU
SEQRES 5 A 267 GLU ALA LYS VAL MET MET ASN LEU SER HIS GLU LYS LEU
SEQRES 6 A 267 VAL GLN LEU TYR GLY VAL CYS THR LYS GLN ARG PRO ILE
SEQRES 7 A 267 PHE ILE ILE THR GLU TYR MET ALA ASN GLY CYS LEU LEU
SEQRES 8 A 267 ASN TYR LEU ARG GLU MET ARG HIS ARG PHE GLN THR GLN
SEQRES 9 A 267 GLN LEU LEU GLU MET CYS LYS ASP VAL CYS GLU ALA MET
SEQRES 10 A 267 GLU TYR LEU GLU SER LYS GLN PHE LEU HIS ARG ASP LEU
SEQRES 11 A 267 ALA ALA ARG ASN CYS LEU VAL ASN ASP GLN GLY VAL VAL
SEQRES 12 A 267 LYS VAL SER ASP PHE GLY LEU SER ARG TYR VAL LEU ASP
SEQRES 13 A 267 ASP GLU TYR THR SER SER VAL GLY SER LYS PHE PRO VAL
SEQRES 14 A 267 ARG TRP SER PRO PRO GLU VAL LEU MET TYR SER LYS PHE
SEQRES 15 A 267 SER SER LYS SER ASP ILE TRP ALA PHE GLY VAL LEU MET
SEQRES 16 A 267 TRP GLU ILE TYR SER LEU GLY LYS MET PRO TYR GLU ARG
SEQRES 17 A 267 PHE THR ASN SER GLU THR ALA GLU HIS ILE ALA GLN GLY
SEQRES 18 A 267 LEU ARG LEU TYR ARG PRO HIS LEU ALA SER GLU LYS VAL
SEQRES 19 A 267 TYR THR ILE MET TYR SER CYS TRP HIS GLU LYS ALA ASP
SEQRES 20 A 267 GLU ARG PRO THR PHE LYS ILE LEU LEU SER ASN ILE LEU
SEQRES 21 A 267 ASP VAL MET ASP GLU GLU SER
SEQRES 1 B 267 GLY HIS MET GLU ILE ASP PRO LYS ASP LEU THR PHE LEU
SEQRES 2 B 267 LYS GLU LEU GLY THR GLY GLN PHE GLY VAL VAL LYS TYR
SEQRES 3 B 267 GLY LYS TRP ARG GLY GLN TYR ASP VAL ALA ILE LYS MET
SEQRES 4 B 267 ILE LYS GLU GLY SER MET SER GLU ASP GLU PHE ILE GLU
SEQRES 5 B 267 GLU ALA LYS VAL MET MET ASN LEU SER HIS GLU LYS LEU
SEQRES 6 B 267 VAL GLN LEU TYR GLY VAL CYS THR LYS GLN ARG PRO ILE
SEQRES 7 B 267 PHE ILE ILE THR GLU TYR MET ALA ASN GLY CYS LEU LEU
SEQRES 8 B 267 ASN TYR LEU ARG GLU MET ARG HIS ARG PHE GLN THR GLN
SEQRES 9 B 267 GLN LEU LEU GLU MET CYS LYS ASP VAL CYS GLU ALA MET
SEQRES 10 B 267 GLU TYR LEU GLU SER LYS GLN PHE LEU HIS ARG ASP LEU
SEQRES 11 B 267 ALA ALA ARG ASN CYS LEU VAL ASN ASP GLN GLY VAL VAL
SEQRES 12 B 267 LYS VAL SER ASP PHE GLY LEU SER ARG TYR VAL LEU ASP
SEQRES 13 B 267 ASP GLU TYR THR SER SER VAL GLY SER LYS PHE PRO VAL
SEQRES 14 B 267 ARG TRP SER PRO PRO GLU VAL LEU MET TYR SER LYS PHE
SEQRES 15 B 267 SER SER LYS SER ASP ILE TRP ALA PHE GLY VAL LEU MET
SEQRES 16 B 267 TRP GLU ILE TYR SER LEU GLY LYS MET PRO TYR GLU ARG
SEQRES 17 B 267 PHE THR ASN SER GLU THR ALA GLU HIS ILE ALA GLN GLY
SEQRES 18 B 267 LEU ARG LEU TYR ARG PRO HIS LEU ALA SER GLU LYS VAL
SEQRES 19 B 267 TYR THR ILE MET TYR SER CYS TRP HIS GLU LYS ALA ASP
SEQRES 20 B 267 GLU ARG PRO THR PHE LYS ILE LEU LEU SER ASN ILE LEU
SEQRES 21 B 267 ASP VAL MET ASP GLU GLU SER
HET 6MV A4000 61
HET 6MV B4000 61
HETNAM 6MV 4-[2-FLUORO-3-(4-OXOQUINAZOLIN-3(4H)-YL)PHENYL]-7-(2-
HETNAM 2 6MV HYDROXYPROPAN-2-YL)-9H-CARBAZOLE-1-CARBOXAMIDE
FORMUL 3 6MV 2(C30 H23 F N4 O3)
FORMUL 5 HOH *167(H2 O)
HELIX 1 AA1 ASP A 398 LYS A 400 5 3
HELIX 2 AA2 SER A 438 ASN A 451 1 14
HELIX 3 AA3 CYS A 481 GLU A 488 1 8
HELIX 4 AA4 GLN A 494 LYS A 515 1 22
HELIX 5 AA5 ALA A 523 ARG A 525 5 3
HELIX 6 AA6 GLY A 541 VAL A 546 5 6
HELIX 7 AA7 ASP A 548 SER A 553 1 6
HELIX 8 AA8 PRO A 560 SER A 564 5 5
HELIX 9 AA9 PRO A 565 SER A 572 1 8
HELIX 10 AB1 SER A 575 SER A 592 1 18
HELIX 11 AB2 THR A 602 GLN A 612 1 11
HELIX 12 AB3 SER A 623 CYS A 633 1 11
HELIX 13 AB4 LYS A 637 ARG A 641 5 5
HELIX 14 AB5 THR A 643 ASP A 656 1 14
HELIX 15 AB6 ASP B 398 LYS B 400 5 3
HELIX 16 AB7 SER B 438 ASN B 451 1 14
HELIX 17 AB8 CYS B 481 GLU B 488 1 8
HELIX 18 AB9 GLN B 494 LYS B 515 1 22
HELIX 19 AC1 ALA B 523 ARG B 525 5 3
HELIX 20 AC2 GLY B 541 VAL B 546 5 6
HELIX 21 AC3 LYS B 558 SER B 564 5 7
HELIX 22 AC4 PRO B 565 SER B 572 1 8
HELIX 23 AC5 SER B 575 SER B 592 1 18
HELIX 24 AC6 THR B 602 GLN B 612 1 11
HELIX 25 AC7 SER B 623 CYS B 633 1 11
HELIX 26 AC8 LYS B 637 ARG B 641 5 5
HELIX 27 AC9 THR B 643 MET B 655 1 13
SHEET 1 AA1 5 LEU A 402 THR A 410 0
SHEET 2 AA1 5 VAL A 415 TRP A 421 -1 O VAL A 416 N LEU A 408
SHEET 3 AA1 5 TYR A 425 ILE A 432 -1 O ILE A 429 N LYS A 417
SHEET 4 AA1 5 ILE A 470 GLU A 475 -1 O ILE A 472 N LYS A 430
SHEET 5 AA1 5 LEU A 460 CYS A 464 -1 N GLY A 462 O ILE A 473
SHEET 1 AA2 2 CYS A 527 VAL A 529 0
SHEET 2 AA2 2 VAL A 535 VAL A 537 -1 O LYS A 536 N LEU A 528
SHEET 1 AA3 5 LEU B 402 THR B 410 0
SHEET 2 AA3 5 VAL B 415 TRP B 421 -1 O VAL B 416 N LEU B 408
SHEET 3 AA3 5 TYR B 425 MET B 431 -1 O ILE B 429 N LYS B 417
SHEET 4 AA3 5 PHE B 471 GLU B 475 -1 O THR B 474 N ALA B 428
SHEET 5 AA3 5 LEU B 460 CYS B 464 -1 N GLY B 462 O ILE B 473
SHEET 1 AA4 2 CYS B 527 VAL B 529 0
SHEET 2 AA4 2 VAL B 535 VAL B 537 -1 O LYS B 536 N LEU B 528
CISPEP 1 ARG A 468 PRO A 469 0 -7.47
SITE 1 AC1 17 LEU A 408 GLY A 409 THR A 410 VAL A 416
SITE 2 AC1 17 ALA A 428 THR A 474 GLU A 475 TYR A 476
SITE 3 AC1 17 MET A 477 ALA A 478 GLY A 480 CYS A 481
SITE 4 AC1 17 ASN A 484 LEU A 528 HOH A4130 HOH A4144
SITE 5 AC1 17 HOH A4165
SITE 1 AC2 18 LEU B 408 GLY B 409 THR B 410 ALA B 428
SITE 2 AC2 18 THR B 474 GLU B 475 TYR B 476 MET B 477
SITE 3 AC2 18 ALA B 478 GLY B 480 CYS B 481 ASN B 484
SITE 4 AC2 18 LEU B 528 HOH B4125 HOH B4129 HOH B4132
SITE 5 AC2 18 HOH B4142 HOH B4152
CRYST1 63.470 45.480 98.350 90.00 93.95 90.00 P 1 21 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 0.015755 0.000000 0.001088 0.00000
SCALE2 0.000000 0.021988 0.000000 0.00000
SCALE3 0.000000 0.000000 0.010192 0.00000
(ATOM LINES ARE NOT SHOWN.)
END
