HEADER TRANSFERASE/TRANSFERASE INHIBITOR 14-OCT-16 5H25
TITLE EED IN COMPLEX WITH PRC2 ALLOSTERIC INHIBITOR COMPOUND 11
COMPND MOL_ID: 1;
COMPND 2 MOLECULE: POLYCOMB PROTEIN EED;
COMPND 3 CHAIN: A, B;
COMPND 4 FRAGMENT: UNP RESIDUES 76-441;
COMPND 5 SYNONYM: HEED,WD PROTEIN ASSOCIATING WITH INTEGRIN CYTOPLASMIC TAILS
COMPND 6 1,WAIT-1;
COMPND 7 ENGINEERED: YES;
COMPND 8 MOL_ID: 2;
COMPND 9 MOLECULE: HISTONE-LYSINE N-METHYLTRANSFERASE EZH2;
COMPND 10 CHAIN: C, D;
COMPND 11 FRAGMENT: UNP RESIDUES 40-68;
COMPND 12 SYNONYM: ENX-1,ENHANCER OF ZESTE HOMOLOG 2,LYSINE N-METHYLTRANSFERASE
COMPND 13 6;
COMPND 14 EC: 2.1.1.43;
COMPND 15 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: EED;
SOURCE 6 EXPRESSION_SYSTEM: ESCHERICHIA COLI;
SOURCE 7 EXPRESSION_SYSTEM_TAXID: 562;
SOURCE 8 EXPRESSION_SYSTEM_VECTOR_TYPE: PLASMID;
SOURCE 9 EXPRESSION_SYSTEM_PLASMID: PGEX-KG;
SOURCE 10 MOL_ID: 2;
SOURCE 11 SYNTHETIC: YES;
SOURCE 12 ORGANISM_SCIENTIFIC: HOMO SAPIENS;
SOURCE 13 ORGANISM_COMMON: HUMAN;
SOURCE 14 ORGANISM_TAXID: 9606
KEYWDS EED, PRC2, INHIBITOR, TRANSFERASE-TRANSFERASE INHIBITOR COMPLEX
EXPDTA X-RAY DIFFRACTION
AUTHOR K.ZHAO,M.ZHAO,X.LUO,H.ZHANG
REVDAT 3 08-NOV-23 5H25 1 REMARK
REVDAT 2 05-APR-17 5H25 1 JRNL
REVDAT 1 25-JAN-17 5H25 0
JRNL AUTH Y.HUANG,J.ZHANG,Z.YU,H.ZHANG,Y.WANG,A.LINGEL,W.QI,J.GU,
JRNL AUTH 2 K.ZHAO,M.D.SHULTZ,L.WANG,X.FU,Y.SUN,Q.ZHANG,X.JIANG,J.ZHANG,
JRNL AUTH 3 C.ZHANG,L.LI,J.ZENG,L.FENG,C.ZHANG,Y.LIU,M.ZHANG,L.ZHANG,
JRNL AUTH 4 M.ZHAO,Z.GAO,X.LIU,D.FANG,H.GUO,Y.MI,T.GABRIEL,M.P.DILLON,
JRNL AUTH 5 P.ATADJA,C.OYANG
JRNL TITL DISCOVERY OF FIRST-IN-CLASS, POTENT, AND ORALLY BIOAVAILABLE
JRNL TITL 2 EMBRYONIC ECTODERM DEVELOPMENT (EED) INHIBITOR WITH ROBUST
JRNL TITL 3 ANTICANCER EFFICACY
JRNL REF J. MED. CHEM. V. 60 2215 2017
JRNL REFN ISSN 1520-4804
JRNL PMID 28092155
JRNL DOI 10.1021/ACS.JMEDCHEM.6B01576
REMARK 2
REMARK 2 RESOLUTION. 2.88 ANGSTROMS.
REMARK 3
REMARK 3 REFINEMENT.
REMARK 3 PROGRAM : BUSTER 2.10.2
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) : 2.88
REMARK 3 RESOLUTION RANGE LOW (ANGSTROMS) : 43.94
REMARK 3 DATA CUTOFF (SIGMA(F)) : 0.000
REMARK 3 COMPLETENESS FOR RANGE (%) : 98.6
REMARK 3 NUMBER OF REFLECTIONS : 19920
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) : 0.189
REMARK 3 R VALUE (WORKING SET) : 0.184
REMARK 3 FREE R VALUE : 0.274
REMARK 3 FREE R VALUE TEST SET SIZE (%) : 5.110
REMARK 3 FREE R VALUE TEST SET COUNT : 1017
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 : 10
REMARK 3 BIN RESOLUTION RANGE HIGH (ANGSTROMS) : 2.88
REMARK 3 BIN RESOLUTION RANGE LOW (ANGSTROMS) : 3.04
REMARK 3 BIN COMPLETENESS (WORKING+TEST) (%) : 93.94
REMARK 3 REFLECTIONS IN BIN (WORKING + TEST SET) : 2706
REMARK 3 BIN R VALUE (WORKING + TEST SET) : NULL
REMARK 3 REFLECTIONS IN BIN (WORKING SET) : 2565
REMARK 3 BIN R VALUE (WORKING SET) : 0.2110
REMARK 3 BIN FREE R VALUE : 0.2980
REMARK 3 BIN FREE R VALUE TEST SET SIZE (%) : 5.21
REMARK 3 BIN FREE R VALUE TEST SET COUNT : 141
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 : 6346
REMARK 3 NUCLEIC ACID ATOMS : 0
REMARK 3 HETEROGEN ATOMS : 40
REMARK 3 SOLVENT ATOMS : 4
REMARK 3
REMARK 3 B VALUES.
REMARK 3 FROM WILSON PLOT (A**2) : 60.44
REMARK 3 MEAN B VALUE (OVERALL, A**2) : 49.26
REMARK 3 OVERALL ANISOTROPIC B VALUE.
REMARK 3 B11 (A**2) : -26.11190
REMARK 3 B22 (A**2) : 13.15970
REMARK 3 B33 (A**2) : 12.95210
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 COORDINATE ERROR.
REMARK 3 ESD FROM LUZZATI PLOT (A) : 0.340
REMARK 3 DPI (BLOW EQ-10) BASED ON R VALUE (A) : NULL
REMARK 3 DPI (BLOW EQ-9) BASED ON FREE R VALUE (A) : 0.441
REMARK 3 DPI (CRUICKSHANK) BASED ON R VALUE (A) : NULL
REMARK 3 DPI (CRUICKSHANK) BASED ON FREE R VALUE (A) : NULL
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 : 0.904
REMARK 3 CORRELATION COEFFICIENT FO-FC FREE : 0.832
REMARK 3
REMARK 3 NUMBER OF GEOMETRIC FUNCTION TERMS DEFINED : 15
REMARK 3 TERM COUNT WEIGHT FUNCTION.
REMARK 3 BOND LENGTHS : 6548 ; 2.000 ; HARMONIC
REMARK 3 BOND ANGLES : 8858 ; 2.000 ; HARMONIC
REMARK 3 TORSION ANGLES : 2296 ; 2.000 ; SINUSOIDAL
REMARK 3 TRIGONAL CARBON PLANES : 169 ; 2.000 ; HARMONIC
REMARK 3 GENERAL PLANES : 939 ; 5.000 ; HARMONIC
REMARK 3 ISOTROPIC THERMAL FACTORS : 6548 ; 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 : 830 ; 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 : 7365 ; 4.000 ; SEMIHARMONIC
REMARK 3
REMARK 3 RMS DEVIATIONS FROM IDEAL VALUES.
REMARK 3 BOND LENGTHS (A) : 0.010
REMARK 3 BOND ANGLES (DEGREES) : 1.18
REMARK 3 PEPTIDE OMEGA TORSION ANGLES (DEGREES) : 3.03
REMARK 3 OTHER TORSION ANGLES (DEGREES) : 21.54
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 5H25 COMPLIES WITH FORMAT V. 3.30, 13-JUL-11
REMARK 100
REMARK 100 THIS ENTRY HAS BEEN PROCESSED BY PDBJ ON 17-OCT-16.
REMARK 100 THE DEPOSITION ID IS D_1300001874.
REMARK 200
REMARK 200 EXPERIMENTAL DETAILS
REMARK 200 EXPERIMENT TYPE : X-RAY DIFFRACTION
REMARK 200 DATE OF DATA COLLECTION : 08-JAN-13
REMARK 200 TEMPERATURE (KELVIN) : 100
REMARK 200 PH : 8.0
REMARK 200 NUMBER OF CRYSTALS USED : 1
REMARK 200
REMARK 200 SYNCHROTRON (Y/N) : Y
REMARK 200 RADIATION SOURCE : SSRF
REMARK 200 BEAMLINE : BL17U
REMARK 200 X-RAY GENERATOR MODEL : NULL
REMARK 200 MONOCHROMATIC OR LAUE (M/L) : M
REMARK 200 WAVELENGTH OR RANGE (A) : 0.978524
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 : NULL
REMARK 200 DATA SCALING SOFTWARE : SCALEPACK
REMARK 200
REMARK 200 NUMBER OF UNIQUE REFLECTIONS : 19963
REMARK 200 RESOLUTION RANGE HIGH (A) : 2.880
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 (%) : 99.4
REMARK 200 DATA REDUNDANCY : 5.100
REMARK 200 R MERGE (I) : 0.11000
REMARK 200 R SYM (I) : NULL
REMARK 200 <I/SIGMA(I)> FOR THE DATA SET : 6.9000
REMARK 200
REMARK 200 IN THE HIGHEST RESOLUTION SHELL.
REMARK 200 HIGHEST RESOLUTION SHELL, RANGE HIGH (A) : 2.88
REMARK 200 HIGHEST RESOLUTION SHELL, RANGE LOW (A) : 3.00
REMARK 200 COMPLETENESS FOR SHELL (%) : 99.8
REMARK 200 DATA REDUNDANCY IN SHELL : 5.20
REMARK 200 R MERGE FOR SHELL (I) : 0.48500
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: 2QXV
REMARK 200
REMARK 200 REMARK: NULL
REMARK 280
REMARK 280 CRYSTAL
REMARK 280 SOLVENT CONTENT, VS (%): 47.18
REMARK 280 MATTHEWS COEFFICIENT, VM (ANGSTROMS**3/DA): 2.33
REMARK 280
REMARK 280 CRYSTALLIZATION CONDITIONS: 0.1 M TRIS, 16% PEG 8000, 10 MM BETA
REMARK 280 -NICOTINAMIDE MONONUCLEOTIDE, PH 8.0, VAPOR DIFFUSION, SITTING
REMARK 280 DROP, TEMPERATURE 293K
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 47.37350
REMARK 290 SMTRY2 3 0.000000 1.000000 0.000000 89.68950
REMARK 290 SMTRY3 3 0.000000 0.000000 -1.000000 0.00000
REMARK 290 SMTRY1 4 1.000000 0.000000 0.000000 47.37350
REMARK 290 SMTRY2 4 0.000000 -1.000000 0.000000 89.68950
REMARK 290 SMTRY3 4 0.000000 0.000000 -1.000000 0.00000
REMARK 290
REMARK 290 REMARK: NULL
REMARK 300
REMARK 300 BIOMOLECULE: 1, 2
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 SOFTWARE DETERMINED QUATERNARY STRUCTURE: DIMERIC
REMARK 350 SOFTWARE USED: PISA
REMARK 350 TOTAL BURIED SURFACE AREA: 2920 ANGSTROM**2
REMARK 350 SURFACE AREA OF THE COMPLEX: 16120 ANGSTROM**2
REMARK 350 CHANGE IN SOLVENT FREE ENERGY: -15.0 KCAL/MOL
REMARK 350 APPLY THE FOLLOWING TO CHAINS: A, C
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 AUTHOR DETERMINED BIOLOGICAL UNIT: DIMERIC
REMARK 350 SOFTWARE DETERMINED QUATERNARY STRUCTURE: DIMERIC
REMARK 350 SOFTWARE USED: PISA
REMARK 350 TOTAL BURIED SURFACE AREA: 2950 ANGSTROM**2
REMARK 350 SURFACE AREA OF THE COMPLEX: 15520 ANGSTROM**2
REMARK 350 CHANGE IN SOLVENT FREE ENERGY: -15.0 KCAL/MOL
REMARK 350 APPLY THE FOLLOWING TO CHAINS: B, D
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 75
REMARK 465 LYS A 76
REMARK 465 ARG A 441
REMARK 465 GLY B 75
REMARK 465 LYS B 76
REMARK 465 ASN B 281
REMARK 465 PRO B 282
REMARK 465 ASN B 283
REMARK 465 LYS B 284
REMARK 465 THR B 285
REMARK 465 ASN B 286
REMARK 465 ARG B 287
REMARK 465 ARG B 441
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 SER A 118 -143.48 54.60
REMARK 500 LEU A 135 -69.74 -107.82
REMARK 500 ASN A 157 -71.68 -75.78
REMARK 500 LYS A 184 145.18 -172.98
REMARK 500 HIS A 213 -4.05 77.89
REMARK 500 HIS A 258 -3.72 69.08
REMARK 500 LYS A 284 -15.39 -175.90
REMARK 500 SER A 323 -155.78 -134.40
REMARK 500 GLU A 325 13.13 -61.30
REMARK 500 MET A 336 -33.60 -36.72
REMARK 500 SER A 346 31.86 -95.73
REMARK 500 TYR A 365 31.52 78.82
REMARK 500 PRO A 396 1.79 -65.29
REMARK 500 HIS A 407 -2.53 -57.64
REMARK 500 PRO B 95 151.15 -47.49
REMARK 500 ASP B 109 155.43 -48.83
REMARK 500 SER B 118 -139.83 50.19
REMARK 500 ASN B 119 30.37 -93.61
REMARK 500 ASP B 212 6.48 -67.51
REMARK 500 HIS B 213 -4.78 81.74
REMARK 500 HIS B 258 -7.34 71.97
REMARK 500 PHE B 299 152.63 178.03
REMARK 500 SER B 323 -142.47 -127.80
REMARK 500 GLU B 325 24.99 -66.45
REMARK 500 TYR B 365 50.99 73.27
REMARK 500 GLN D 62 41.15 -87.10
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 LQH A 501
REMARK 800
REMARK 800 SITE_IDENTIFIER: AC2
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: binding site for residue LQH B 501
REMARK 900
REMARK 900 RELATED ENTRIES
REMARK 900 RELATED ID: 5H13 RELATED DB: PDB
REMARK 900 RELATED ID: 5H14 RELATED DB: PDB
REMARK 900 RELATED ID: 5H15 RELATED DB: PDB
REMARK 900 RELATED ID: 5H17 RELATED DB: PDB
REMARK 900 RELATED ID: 5H19 RELATED DB: PDB
REMARK 900 RELATED ID: 5H24 RELATED DB: PDB
DBREF 5H25 A 76 441 UNP O75530 EED_HUMAN 76 441
DBREF 5H25 B 76 441 UNP O75530 EED_HUMAN 76 441
DBREF 5H25 C 40 68 UNP Q15910 EZH2_HUMAN 40 68
DBREF 5H25 D 40 68 UNP Q15910 EZH2_HUMAN 40 68
SEQADV 5H25 GLY A 75 UNP O75530 EXPRESSION TAG
SEQADV 5H25 GLY B 75 UNP O75530 EXPRESSION TAG
SEQRES 1 A 367 GLY LYS LYS CYS LYS TYR SER PHE LYS CYS VAL ASN SER
SEQRES 2 A 367 LEU LYS GLU ASP HIS ASN GLN PRO LEU PHE GLY VAL GLN
SEQRES 3 A 367 PHE ASN TRP HIS SER LYS GLU GLY ASP PRO LEU VAL PHE
SEQRES 4 A 367 ALA THR VAL GLY SER ASN ARG VAL THR LEU TYR GLU CYS
SEQRES 5 A 367 HIS SER GLN GLY GLU ILE ARG LEU LEU GLN SER TYR VAL
SEQRES 6 A 367 ASP ALA ASP ALA ASP GLU ASN PHE TYR THR CYS ALA TRP
SEQRES 7 A 367 THR TYR ASP SER ASN THR SER HIS PRO LEU LEU ALA VAL
SEQRES 8 A 367 ALA GLY SER ARG GLY ILE ILE ARG ILE ILE ASN PRO ILE
SEQRES 9 A 367 THR MET GLN CYS ILE LYS HIS TYR VAL GLY HIS GLY ASN
SEQRES 10 A 367 ALA ILE ASN GLU LEU LYS PHE HIS PRO ARG ASP PRO ASN
SEQRES 11 A 367 LEU LEU LEU SER VAL SER LYS ASP HIS ALA LEU ARG LEU
SEQRES 12 A 367 TRP ASN ILE GLN THR ASP THR LEU VAL ALA ILE PHE GLY
SEQRES 13 A 367 GLY VAL GLU GLY HIS ARG ASP GLU VAL LEU SER ALA ASP
SEQRES 14 A 367 TYR ASP LEU LEU GLY GLU LYS ILE MET SER CYS GLY MET
SEQRES 15 A 367 ASP HIS SER LEU LYS LEU TRP ARG ILE ASN SER LYS ARG
SEQRES 16 A 367 MET MET ASN ALA ILE LYS GLU SER TYR ASP TYR ASN PRO
SEQRES 17 A 367 ASN LYS THR ASN ARG PRO PHE ILE SER GLN LYS ILE HIS
SEQRES 18 A 367 PHE PRO ASP PHE SER THR ARG ASP ILE HIS ARG ASN TYR
SEQRES 19 A 367 VAL ASP CYS VAL ARG TRP LEU GLY ASP LEU ILE LEU SER
SEQRES 20 A 367 LYS SER CYS GLU ASN ALA ILE VAL CYS TRP LYS PRO GLY
SEQRES 21 A 367 LYS MET GLU ASP ASP ILE ASP LYS ILE LYS PRO SER GLU
SEQRES 22 A 367 SER ASN VAL THR ILE LEU GLY ARG PHE ASP TYR SER GLN
SEQRES 23 A 367 CYS ASP ILE TRP TYR MET ARG PHE SER MET ASP PHE TRP
SEQRES 24 A 367 GLN LYS MET LEU ALA LEU GLY ASN GLN VAL GLY LYS LEU
SEQRES 25 A 367 TYR VAL TRP ASP LEU GLU VAL GLU ASP PRO HIS LYS ALA
SEQRES 26 A 367 LYS CYS THR THR LEU THR HIS HIS LYS CYS GLY ALA ALA
SEQRES 27 A 367 ILE ARG GLN THR SER PHE SER ARG ASP SER SER ILE LEU
SEQRES 28 A 367 ILE ALA VAL CYS ASP ASP ALA SER ILE TRP ARG TRP ASP
SEQRES 29 A 367 ARG LEU ARG
SEQRES 1 B 367 GLY LYS LYS CYS LYS TYR SER PHE LYS CYS VAL ASN SER
SEQRES 2 B 367 LEU LYS GLU ASP HIS ASN GLN PRO LEU PHE GLY VAL GLN
SEQRES 3 B 367 PHE ASN TRP HIS SER LYS GLU GLY ASP PRO LEU VAL PHE
SEQRES 4 B 367 ALA THR VAL GLY SER ASN ARG VAL THR LEU TYR GLU CYS
SEQRES 5 B 367 HIS SER GLN GLY GLU ILE ARG LEU LEU GLN SER TYR VAL
SEQRES 6 B 367 ASP ALA ASP ALA ASP GLU ASN PHE TYR THR CYS ALA TRP
SEQRES 7 B 367 THR TYR ASP SER ASN THR SER HIS PRO LEU LEU ALA VAL
SEQRES 8 B 367 ALA GLY SER ARG GLY ILE ILE ARG ILE ILE ASN PRO ILE
SEQRES 9 B 367 THR MET GLN CYS ILE LYS HIS TYR VAL GLY HIS GLY ASN
SEQRES 10 B 367 ALA ILE ASN GLU LEU LYS PHE HIS PRO ARG ASP PRO ASN
SEQRES 11 B 367 LEU LEU LEU SER VAL SER LYS ASP HIS ALA LEU ARG LEU
SEQRES 12 B 367 TRP ASN ILE GLN THR ASP THR LEU VAL ALA ILE PHE GLY
SEQRES 13 B 367 GLY VAL GLU GLY HIS ARG ASP GLU VAL LEU SER ALA ASP
SEQRES 14 B 367 TYR ASP LEU LEU GLY GLU LYS ILE MET SER CYS GLY MET
SEQRES 15 B 367 ASP HIS SER LEU LYS LEU TRP ARG ILE ASN SER LYS ARG
SEQRES 16 B 367 MET MET ASN ALA ILE LYS GLU SER TYR ASP TYR ASN PRO
SEQRES 17 B 367 ASN LYS THR ASN ARG PRO PHE ILE SER GLN LYS ILE HIS
SEQRES 18 B 367 PHE PRO ASP PHE SER THR ARG ASP ILE HIS ARG ASN TYR
SEQRES 19 B 367 VAL ASP CYS VAL ARG TRP LEU GLY ASP LEU ILE LEU SER
SEQRES 20 B 367 LYS SER CYS GLU ASN ALA ILE VAL CYS TRP LYS PRO GLY
SEQRES 21 B 367 LYS MET GLU ASP ASP ILE ASP LYS ILE LYS PRO SER GLU
SEQRES 22 B 367 SER ASN VAL THR ILE LEU GLY ARG PHE ASP TYR SER GLN
SEQRES 23 B 367 CYS ASP ILE TRP TYR MET ARG PHE SER MET ASP PHE TRP
SEQRES 24 B 367 GLN LYS MET LEU ALA LEU GLY ASN GLN VAL GLY LYS LEU
SEQRES 25 B 367 TYR VAL TRP ASP LEU GLU VAL GLU ASP PRO HIS LYS ALA
SEQRES 26 B 367 LYS CYS THR THR LEU THR HIS HIS LYS CYS GLY ALA ALA
SEQRES 27 B 367 ILE ARG GLN THR SER PHE SER ARG ASP SER SER ILE LEU
SEQRES 28 B 367 ILE ALA VAL CYS ASP ASP ALA SER ILE TRP ARG TRP ASP
SEQRES 29 B 367 ARG LEU ARG
SEQRES 1 C 29 SER MET PHE SER SER ASN ARG GLN LYS ILE LEU GLU ARG
SEQRES 2 C 29 THR GLU ILE LEU ASN GLN GLU TRP LYS GLN ARG ARG ILE
SEQRES 3 C 29 GLN PRO VAL
SEQRES 1 D 29 SER MET PHE SER SER ASN ARG GLN LYS ILE LEU GLU ARG
SEQRES 2 D 29 THR GLU ILE LEU ASN GLN GLU TRP LYS GLN ARG ARG ILE
SEQRES 3 D 29 GLN PRO VAL
HET LQH A 501 20
HET LQH B 501 20
HETNAM LQH 5-(2-FLUOROPHENYL)-2,3-DIHYDROIMIDAZO[2,1-
HETNAM 2 LQH A]ISOQUINOLINE
FORMUL 5 LQH 2(C17 H13 F N2)
FORMUL 7 HOH *4(H2 O)
HELIX 1 AA1 SER A 267 TYR A 280 1 14
HELIX 2 AA2 ASP A 339 ILE A 343 5 5
HELIX 3 AA3 SER B 267 TYR B 280 1 14
HELIX 4 AA4 MET C 41 GLN C 62 1 22
HELIX 5 AA5 MET D 41 GLN D 62 1 22
SHEET 1 AA1 4 PHE A 82 LYS A 89 0
SHEET 2 AA1 4 SER A 433 ARG A 439 -1 O ARG A 436 N ASN A 86
SHEET 3 AA1 4 ILE A 424 CYS A 429 -1 N LEU A 425 O TRP A 437
SHEET 4 AA1 4 ILE A 413 PHE A 418 -1 N SER A 417 O ILE A 426
SHEET 1 AA2 4 GLY A 98 PHE A 101 0
SHEET 2 AA2 4 LEU A 111 GLY A 117 -1 O ALA A 114 N GLN A 100
SHEET 3 AA2 4 ARG A 120 HIS A 127 -1 O THR A 122 N THR A 115
SHEET 4 AA2 4 GLU A 131 VAL A 139 -1 O TYR A 138 N VAL A 121
SHEET 1 AA3 4 PHE A 147 TYR A 154 0
SHEET 2 AA3 4 PRO A 161 GLY A 167 -1 O ALA A 164 N ALA A 151
SHEET 3 AA3 4 ILE A 172 ASN A 176 -1 O ILE A 175 N LEU A 163
SHEET 4 AA3 4 GLN A 181 TYR A 186 -1 O LYS A 184 N ILE A 174
SHEET 1 AA4 5 ILE A 193 PHE A 198 0
SHEET 2 AA4 5 LEU A 205 SER A 210 -1 O LEU A 207 N LYS A 197
SHEET 3 AA4 5 LEU A 215 ASN A 219 -1 O ARG A 216 N SER A 208
SHEET 4 AA4 5 THR A 224 PHE A 229 -1 O PHE A 229 N LEU A 215
SHEET 5 AA4 5 GLN A 292 ILE A 294 1 O ILE A 294 N ILE A 228
SHEET 1 AA5 4 VAL A 239 TYR A 244 0
SHEET 2 AA5 4 LYS A 250 GLY A 255 -1 O CYS A 254 N LEU A 240
SHEET 3 AA5 4 LEU A 260 ARG A 264 -1 O LYS A 261 N SER A 253
SHEET 4 AA5 4 PHE A 299 THR A 301 -1 O PHE A 299 N LEU A 262
SHEET 1 AA6 4 CYS A 311 LEU A 315 0
SHEET 2 AA6 4 LEU A 318 LYS A 322 -1 O LEU A 318 N LEU A 315
SHEET 3 AA6 4 ALA A 327 PRO A 333 -1 O TRP A 331 N ILE A 319
SHEET 4 AA6 4 VAL A 350 ASP A 357 -1 O GLY A 354 N CYS A 330
SHEET 1 AA7 3 SER A 369 MET A 370 0
SHEET 2 AA7 3 MET A 376 GLY A 380 -1 O ALA A 378 N SER A 369
SHEET 3 AA7 3 LEU A 386 ASP A 390 -1 O TYR A 387 N LEU A 379
SHEET 1 AA8 4 PHE B 82 LYS B 89 0
SHEET 2 AA8 4 SER B 433 ARG B 439 -1 O ASP B 438 N LYS B 83
SHEET 3 AA8 4 ILE B 424 CYS B 429 -1 N LEU B 425 O TRP B 437
SHEET 4 AA8 4 ILE B 413 PHE B 418 -1 N SER B 417 O ILE B 426
SHEET 1 AA9 4 GLY B 98 PHE B 101 0
SHEET 2 AA9 4 LEU B 111 GLY B 117 -1 O ALA B 114 N GLN B 100
SHEET 3 AA9 4 ARG B 120 CYS B 126 -1 O CYS B 126 N LEU B 111
SHEET 4 AA9 4 ILE B 132 GLN B 136 -1 O GLN B 136 N LEU B 123
SHEET 1 AB1 4 PHE B 147 ASP B 155 0
SHEET 2 AB1 4 HIS B 160 GLY B 167 -1 O ALA B 164 N ALA B 151
SHEET 3 AB1 4 ILE B 172 ASN B 176 -1 O ILE B 175 N LEU B 163
SHEET 4 AB1 4 GLN B 181 TYR B 186 -1 O GLN B 181 N ASN B 176
SHEET 1 AB2 5 ILE B 193 PHE B 198 0
SHEET 2 AB2 5 LEU B 205 SER B 210 -1 O LEU B 207 N LYS B 197
SHEET 3 AB2 5 LEU B 215 ASN B 219 -1 O ARG B 216 N SER B 208
SHEET 4 AB2 5 THR B 224 PHE B 229 -1 O PHE B 229 N LEU B 215
SHEET 5 AB2 5 GLN B 292 ILE B 294 1 O ILE B 294 N ILE B 228
SHEET 1 AB3 4 VAL B 239 TYR B 244 0
SHEET 2 AB3 4 LYS B 250 GLY B 255 -1 O CYS B 254 N SER B 241
SHEET 3 AB3 4 LEU B 260 ARG B 264 -1 O LYS B 261 N SER B 253
SHEET 4 AB3 4 PHE B 299 THR B 301 -1 O THR B 301 N LEU B 260
SHEET 1 AB4 4 CYS B 311 LEU B 315 0
SHEET 2 AB4 4 LEU B 318 LYS B 322 -1 O LEU B 318 N LEU B 315
SHEET 3 AB4 4 ALA B 327 PRO B 333 -1 O VAL B 329 N SER B 321
SHEET 4 AB4 4 VAL B 350 ASP B 357 -1 O LEU B 353 N CYS B 330
SHEET 1 AB5 4 SER B 369 MET B 370 0
SHEET 2 AB5 4 MET B 376 GLY B 380 -1 O ALA B 378 N SER B 369
SHEET 3 AB5 4 LEU B 386 ASP B 390 -1 O TYR B 387 N LEU B 379
SHEET 4 AB5 4 LYS B 400 LEU B 404 -1 O CYS B 401 N VAL B 388
SSBOND 1 CYS A 78 CYS A 401 1555 1555 2.04
SSBOND 2 CYS B 78 CYS B 401 1555 1555 2.04
SITE 1 AC1 6 PHE A 97 ASN A 146 TYR A 148 ASN A 194
SITE 2 AC1 6 TYR A 365 ARG A 414
SITE 1 AC2 6 PHE B 97 ASN B 146 TYR B 148 ASN B 194
SITE 2 AC2 6 TYR B 365 ARG B 367
CRYST1 94.747 179.379 50.396 90.00 90.00 90.00 P 21 21 2 8
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 0.010554 0.000000 0.000000 0.00000
SCALE2 0.000000 0.005575 0.000000 0.00000
SCALE3 0.000000 0.000000 0.019843 0.00000
(ATOM LINES ARE NOT SHOWN.)
END