HEADER TRANSFERASE/TRANSFERASE INHIBITOR 01-MAR-16 5IIS
TITLE DESIGN, SYNTHESIS AND STRUCTURE ACTIVITY RELATIONSHIP OF POTENT PAN-
TITLE 2 PIM KINASE INHIBITORS DERIVED FROM THE PYRIDYL-AMIDE SCAFFOLD
COMPND MOL_ID: 1;
COMPND 2 MOLECULE: SERINE/THREONINE-PROTEIN KINASE PIM-1;
COMPND 3 CHAIN: A;
COMPND 4 EC: 2.7.11.1;
COMPND 5 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: PIM1;
SOURCE 6 EXPRESSION_SYSTEM: ESCHERICHIA COLI;
SOURCE 7 EXPRESSION_SYSTEM_TAXID: 562
KEYWDS PIM1, MOLONEY MURINE LEUKEMIA, PIM447, KINASE INHIBITOR, TRANSFERASE-
KEYWDS 2 TRANSFERASE INHIBITOR COMPLEX
EXPDTA X-RAY DIFFRACTION
AUTHOR C.BELLAMACINA,D.BUSSIERE,M.BURGER
REVDAT 3 04-MAY-16 5IIS 1 JRNL
REVDAT 2 13-APR-16 5IIS 1 REMARK
REVDAT 1 06-APR-16 5IIS 0
JRNL AUTH G.A.NISHIGUCHI,M.T.BURGER,W.HAN,J.LAN,G.ATALLAH,V.TAMEZ,
JRNL AUTH 2 M.LINDVALL,C.BELLAMACINA,P.GARCIA,P.FEUCHT,T.ZAVOROTINSKAYA,
JRNL AUTH 3 Y.DAI,K.WONG
JRNL TITL DESIGN, SYNTHESIS AND STRUCTURE ACTIVITY RELATIONSHIP OF
JRNL TITL 2 POTENT PAN-PIM KINASE INHIBITORS DERIVED FROM THE PYRIDYL
JRNL TITL 3 CARBOXAMIDE SCAFFOLD.
JRNL REF BIOORG.MED.CHEM.LETT. V. 26 2328 2016
JRNL REFN ESSN 1464-3405
JRNL PMID 26995528
JRNL DOI 10.1016/J.BMCL.2016.03.037
REMARK 2
REMARK 2 RESOLUTION. 2.10 ANGSTROMS.
REMARK 3
REMARK 3 REFINEMENT.
REMARK 3 PROGRAM : BUSTER 2.11.5
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) : 2.10
REMARK 3 RESOLUTION RANGE LOW (ANGSTROMS) : 41.78
REMARK 3 DATA CUTOFF (SIGMA(F)) : NULL
REMARK 3 COMPLETENESS FOR RANGE (%) : 100.0
REMARK 3 NUMBER OF REFLECTIONS : 25621
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) : 0.171
REMARK 3 FREE R VALUE : 0.193
REMARK 3 FREE R VALUE TEST SET SIZE (%) : 5.060
REMARK 3 FREE R VALUE TEST SET COUNT : 1297
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 : 13
REMARK 3 BIN RESOLUTION RANGE HIGH (ANGSTROMS) : 2.10
REMARK 3 BIN RESOLUTION RANGE LOW (ANGSTROMS) : 2.19
REMARK 3 BIN COMPLETENESS (WORKING+TEST) (%) : 99.96
REMARK 3 REFLECTIONS IN BIN (WORKING + TEST SET) : 2890
REMARK 3 BIN R VALUE (WORKING + TEST SET) : 0.1665
REMARK 3 REFLECTIONS IN BIN (WORKING SET) : 2745
REMARK 3 BIN R VALUE (WORKING SET) : 0.1649
REMARK 3 BIN FREE R VALUE : 0.1953
REMARK 3 BIN FREE R VALUE TEST SET SIZE (%) : 5.02
REMARK 3 BIN FREE R VALUE TEST SET COUNT : 145
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 : 2233
REMARK 3 NUCLEIC ACID ATOMS : 0
REMARK 3 HETEROGEN ATOMS : 38
REMARK 3 SOLVENT ATOMS : 209
REMARK 3
REMARK 3 B VALUES.
REMARK 3 FROM WILSON PLOT (A**2) : 29.10
REMARK 3 MEAN B VALUE (OVERALL, A**2) : 35.95
REMARK 3 OVERALL ANISOTROPIC B VALUE.
REMARK 3 B11 (A**2) : 0.05150
REMARK 3 B22 (A**2) : 0.05150
REMARK 3 B33 (A**2) : -0.10300
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) : NULL
REMARK 3 DPI (BLOW EQ-10) BASED ON R VALUE (A) : 0.145
REMARK 3 DPI (BLOW EQ-9) BASED ON FREE R VALUE (A) : 0.127
REMARK 3 DPI (CRUICKSHANK) BASED ON R VALUE (A) : 0.143
REMARK 3 DPI (CRUICKSHANK) BASED ON FREE R VALUE (A) : 0.126
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 : 0.954
REMARK 3 CORRELATION COEFFICIENT FO-FC FREE : 0.949
REMARK 3
REMARK 3 NUMBER OF GEOMETRIC FUNCTION TERMS DEFINED : 15
REMARK 3 TERM COUNT WEIGHT FUNCTION.
REMARK 3 BOND LENGTHS : 2352 ; 2.000 ; HARMONIC
REMARK 3 BOND ANGLES : 3204 ; 2.000 ; HARMONIC
REMARK 3 TORSION ANGLES : 804 ; 2.000 ; SINUSOIDAL
REMARK 3 TRIGONAL CARBON PLANES : 58 ; 2.000 ; HARMONIC
REMARK 3 GENERAL PLANES : 384 ; 5.000 ; HARMONIC
REMARK 3 ISOTROPIC THERMAL FACTORS : 2352 ; 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 : 279 ; 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 : 2816 ; 4.000 ; SEMIHARMONIC
REMARK 3
REMARK 3 RMS DEVIATIONS FROM IDEAL VALUES.
REMARK 3 BOND LENGTHS (A) : 0.010
REMARK 3 BOND ANGLES (DEGREES) : 0.92
REMARK 3 PEPTIDE OMEGA TORSION ANGLES (DEGREES) : 3.19
REMARK 3 OTHER TORSION ANGLES (DEGREES) : 17.05
REMARK 3
REMARK 3 TLS DETAILS
REMARK 3 NUMBER OF TLS GROUPS : 1
REMARK 3
REMARK 3 TLS GROUP : 1
REMARK 3 SELECTION: { A|* }
REMARK 3 ORIGIN FOR THE GROUP (A): -8.4315 40.3983 0.1370
REMARK 3 T TENSOR
REMARK 3 T11: 0.0000 T22: 0.0000
REMARK 3 T33: 0.0000 T12: 0.0000
REMARK 3 T13: 0.0000 T23: 0.0000
REMARK 3 L TENSOR
REMARK 3 L11: 0.0000 L22: 0.0000
REMARK 3 L33: 0.0000 L12: 0.0000
REMARK 3 L13: 0.0000 L23: 0.0000
REMARK 3 S TENSOR
REMARK 3 S11: 0.0000 S12: 0.0000 S13: 0.0000
REMARK 3 S21: 0.0000 S22: 0.0000 S23: 0.0000
REMARK 3 S31: 0.0000 S32: 0.0000 S33: 0.0000
REMARK 3
REMARK 3 OTHER REFINEMENT REMARKS: NULL
REMARK 4
REMARK 4 5IIS COMPLIES WITH FORMAT V. 3.30, 13-JUL-11
REMARK 100
REMARK 100 THIS ENTRY HAS BEEN PROCESSED BY RCSB ON 09-MAR-16.
REMARK 100 THE DEPOSITION ID IS D_1000218861.
REMARK 200
REMARK 200 EXPERIMENTAL DETAILS
REMARK 200 EXPERIMENT TYPE : X-RAY DIFFRACTION
REMARK 200 DATE OF DATA COLLECTION : 02-MAY-07
REMARK 200 TEMPERATURE (KELVIN) : NULL
REMARK 200 PH : 5.5
REMARK 200 NUMBER OF CRYSTALS USED : 1
REMARK 200
REMARK 200 SYNCHROTRON (Y/N) : Y
REMARK 200 RADIATION SOURCE : SSRL
REMARK 200 BEAMLINE : BL11-1
REMARK 200 X-RAY GENERATOR MODEL : NULL
REMARK 200 MONOCHROMATIC OR LAUE (M/L) : M
REMARK 200 WAVELENGTH OR RANGE (A) : 0.998
REMARK 200 MONOCHROMATOR : NULL
REMARK 200 OPTICS : NULL
REMARK 200
REMARK 200 DETECTOR TYPE : CCD
REMARK 200 DETECTOR MANUFACTURER : MARMOSAIC 325 MM CCD
REMARK 200 INTENSITY-INTEGRATION SOFTWARE : MOSFLM
REMARK 200 DATA SCALING SOFTWARE : SCALA
REMARK 200
REMARK 200 NUMBER OF UNIQUE REFLECTIONS : 29642
REMARK 200 RESOLUTION RANGE HIGH (A) : 2.100
REMARK 200 RESOLUTION RANGE LOW (A) : 84.515
REMARK 200 REJECTION CRITERIA (SIGMA(I)) : NULL
REMARK 200
REMARK 200 OVERALL.
REMARK 200 COMPLETENESS FOR RANGE (%) : 100.0
REMARK 200 DATA REDUNDANCY : 7.600
REMARK 200 R MERGE (I) : 0.06800
REMARK 200 R SYM (I) : NULL
REMARK 200 <I/SIGMA(I)> FOR THE DATA SET : 21.3000
REMARK 200
REMARK 200 IN THE HIGHEST RESOLUTION SHELL.
REMARK 200 HIGHEST RESOLUTION SHELL, RANGE HIGH (A) : 2.10
REMARK 200 HIGHEST RESOLUTION SHELL, RANGE LOW (A) : 2.11
REMARK 200 COMPLETENESS FOR SHELL (%) : 100.0
REMARK 200 DATA REDUNDANCY IN SHELL : 7.60
REMARK 200 R MERGE FOR SHELL (I) : 0.41600
REMARK 200 R SYM FOR SHELL (I) : NULL
REMARK 200 <I/SIGMA(I)> FOR SHELL : 4.600
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: NULL
REMARK 200
REMARK 200 REMARK: P6(5)
REMARK 280
REMARK 280 CRYSTAL
REMARK 280 SOLVENT CONTENT, VS (%): 64.56
REMARK 280 MATTHEWS COEFFICIENT, VM (ANGSTROMS**3/DA): 3.47
REMARK 280
REMARK 280 CRYSTALLIZATION CONDITIONS: 0.5-1.0 MM (NH4)2HPO4; 0.1 M SODIUM
REMARK 280 CITRATE PH 5.5; 250 MM SODIUM CHLORIDE, VAPOR DIFFUSION, HANGING
REMARK 280 DROP, TEMPERATURE 298K
REMARK 290
REMARK 290 CRYSTALLOGRAPHIC SYMMETRY
REMARK 290 SYMMETRY OPERATORS FOR SPACE GROUP: P 65
REMARK 290
REMARK 290 SYMOP SYMMETRY
REMARK 290 NNNMMM OPERATOR
REMARK 290 1555 X,Y,Z
REMARK 290 2555 -Y,X-Y,Z+2/3
REMARK 290 3555 -X+Y,-X,Z+1/3
REMARK 290 4555 -X,-Y,Z+1/2
REMARK 290 5555 Y,-X+Y,Z+1/6
REMARK 290 6555 X-Y,X,Z+5/6
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 53.73933
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 26.86967
REMARK 290 SMTRY1 4 -1.000000 0.000000 0.000000 0.00000
REMARK 290 SMTRY2 4 0.000000 -1.000000 0.000000 0.00000
REMARK 290 SMTRY3 4 0.000000 0.000000 1.000000 40.30450
REMARK 290 SMTRY1 5 0.500000 0.866025 0.000000 0.00000
REMARK 290 SMTRY2 5 -0.866025 0.500000 0.000000 0.00000
REMARK 290 SMTRY3 5 0.000000 0.000000 1.000000 13.43483
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 67.17417
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 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 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 SER A 306
REMARK 465 LEU A 307
REMARK 465 SER A 308
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 GLU A 35 CG CD OE1 OE2
REMARK 500
REMARK 500 GEOMETRY AND STEREOCHEMISTRY
REMARK 500 SUBTOPIC: COVALENT BOND LENGTHS
REMARK 500
REMARK 500 THE STEREOCHEMICAL PARAMETERS OF THE FOLLOWING RESIDUES
REMARK 500 HAVE VALUES WHICH DEVIATE FROM EXPECTED VALUES BY MORE
REMARK 500 THAN 6*RMSD (M=MODEL NUMBER; RES=RESIDUE NAME; C=CHAIN
REMARK 500 IDENTIFIER; SSEQ=SEQUENCE NUMBER; I=INSERTION CODE).
REMARK 500
REMARK 500 STANDARD TABLE:
REMARK 500 FORMAT: (10X,I3,1X,2(A3,1X,A1,I4,A1,1X,A4,3X),1X,F6.3)
REMARK 500
REMARK 500 EXPECTED VALUES PROTEIN: ENGH AND HUBER, 1999
REMARK 500 EXPECTED VALUES NUCLEIC ACID: CLOWNEY ET AL 1996
REMARK 500
REMARK 500 M RES CSSEQI ATM1 RES CSSEQI ATM2 DEVIATION
REMARK 500 MET A 290 SD MET A 290 CE -0.422
REMARK 500
REMARK 500 REMARK: NULL
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 98 -158.18 -156.76
REMARK 500 ASP A 167 45.80 -149.79
REMARK 500 ASP A 186 84.09 61.28
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 PEG A 401
REMARK 800
REMARK 800 SITE_IDENTIFIER: AC2
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: binding site for residue 6CB A 402
DBREF 5IIS A 32 308 UNP P11309 PIM1_HUMAN 32 308
SEQRES 1 A 277 GLU PRO LEU GLU SER GLN TYR GLN VAL GLY PRO LEU LEU
SEQRES 2 A 277 GLY SER GLY GLY PHE GLY SER VAL TYR SER GLY ILE ARG
SEQRES 3 A 277 VAL SER ASP ASN LEU PRO VAL ALA ILE LYS HIS VAL GLU
SEQRES 4 A 277 LYS ASP ARG ILE SER ASP TRP GLY GLU LEU PRO ASN GLY
SEQRES 5 A 277 THR ARG VAL PRO MET GLU VAL VAL LEU LEU LYS LYS VAL
SEQRES 6 A 277 SER SER GLY PHE SER GLY VAL ILE ARG LEU LEU ASP TRP
SEQRES 7 A 277 PHE GLU ARG PRO ASP SER PHE VAL LEU ILE LEU GLU ARG
SEQRES 8 A 277 PRO GLU PRO VAL GLN ASP LEU PHE ASP PHE ILE THR GLU
SEQRES 9 A 277 ARG GLY ALA LEU GLN GLU GLU LEU ALA ARG SER PHE PHE
SEQRES 10 A 277 TRP GLN VAL LEU GLU ALA VAL ARG HIS CYS HIS ASN CYS
SEQRES 11 A 277 GLY VAL LEU HIS ARG ASP ILE LYS ASP GLU ASN ILE LEU
SEQRES 12 A 277 ILE ASP LEU ASN ARG GLY GLU LEU LYS LEU ILE ASP PHE
SEQRES 13 A 277 GLY SER GLY ALA LEU LEU LYS ASP THR VAL TYR THR ASP
SEQRES 14 A 277 PHE ASP GLY THR ARG VAL TYR SER PRO PRO GLU TRP ILE
SEQRES 15 A 277 ARG TYR HIS ARG TYR HIS GLY ARG SER ALA ALA VAL TRP
SEQRES 16 A 277 SER LEU GLY ILE LEU LEU TYR ASP MET VAL CYS GLY ASP
SEQRES 17 A 277 ILE PRO PHE GLU HIS ASP GLU GLU ILE ILE ARG GLY GLN
SEQRES 18 A 277 VAL PHE PHE ARG GLN ARG VAL SER SEP GLU CYS GLN HIS
SEQRES 19 A 277 LEU ILE ARG TRP CYS LEU ALA LEU ARG PRO SER ASP ARG
SEQRES 20 A 277 PRO THR PHE GLU GLU ILE GLN ASN HIS PRO TRP MET GLN
SEQRES 21 A 277 ASP VAL LEU LEU PRO GLN GLU THR ALA GLU ILE HIS LEU
SEQRES 22 A 277 HIS SER LEU SER
MODRES 5IIS SEP A 261 SER MODIFIED RESIDUE
HET SEP A 261 10
HET PEG A 401 7
HET 6CB A 402 50
HETNAM SEP PHOSPHOSERINE
HETNAM PEG DI(HYDROXYETHYL)ETHER
HETNAM 6CB 3-AMINO-N-(2'-AMINO-6'-METHYL[4,4'-BIPYRIDIN]-3-YL)-6-
HETNAM 2 6CB (2-FLUOROPHENYL)PYRIDINE-2-CARBOXAMIDE
HETSYN SEP PHOSPHONOSERINE
FORMUL 1 SEP C3 H8 N O6 P
FORMUL 2 PEG C4 H10 O3
FORMUL 3 6CB C23 H19 F N6 O
FORMUL 4 HOH *209(H2 O)
HELIX 1 AA1 PRO A 33 GLN A 37 1 5
HELIX 2 AA2 ASP A 72 ILE A 74 5 3
HELIX 3 AA3 MET A 88 VAL A 96 1 9
HELIX 4 AA4 LEU A 129 GLY A 137 1 9
HELIX 5 AA5 GLN A 140 CYS A 161 1 22
HELIX 6 AA6 LYS A 169 GLU A 171 5 3
HELIX 7 AA7 THR A 204 SER A 208 5 5
HELIX 8 AA8 PRO A 209 HIS A 216 1 8
HELIX 9 AA9 HIS A 219 GLY A 238 1 20
HELIX 10 AB1 HIS A 244 GLY A 251 1 8
HELIX 11 AB2 SER A 260 LEU A 271 1 12
HELIX 12 AB3 ARG A 274 ARG A 278 5 5
HELIX 13 AB4 THR A 280 ASN A 286 1 7
HELIX 14 AB5 HIS A 287 GLN A 291 5 5
HELIX 15 AB6 LEU A 295 LEU A 304 1 10
SHEET 1 AA1 5 TYR A 38 GLY A 47 0
SHEET 2 AA1 5 GLY A 50 ARG A 57 -1 O SER A 54 N GLY A 41
SHEET 3 AA1 5 PRO A 63 GLU A 70 -1 O ILE A 66 N TYR A 53
SHEET 4 AA1 5 SER A 115 GLU A 121 -1 O LEU A 118 N LYS A 67
SHEET 5 AA1 5 LEU A 106 GLU A 111 -1 N ASP A 108 O ILE A 119
SHEET 1 AA2 2 TRP A 77 GLU A 79 0
SHEET 2 AA2 2 ARG A 85 PRO A 87 -1 O VAL A 86 N GLY A 78
SHEET 1 AA3 3 VAL A 126 ASP A 128 0
SHEET 2 AA3 3 ILE A 173 ASP A 176 -1 O ILE A 175 N GLN A 127
SHEET 3 AA3 3 GLU A 181 LEU A 184 -1 O GLU A 181 N ASP A 176
SHEET 1 AA4 2 VAL A 163 LEU A 164 0
SHEET 2 AA4 2 ALA A 191 LEU A 192 -1 O ALA A 191 N LEU A 164
LINK C SER A 260 N SEP A 261 1555 1555 1.34
LINK C SEP A 261 N GLU A 262 1555 1555 1.34
CISPEP 1 GLU A 124 PRO A 125 0 0.44
SITE 1 AC1 6 PHE A 130 ILE A 133 ASP A 170 TYR A 207
SITE 2 AC1 6 ASP A 234 ASP A 239
SITE 1 AC2 14 LEU A 44 PHE A 49 ALA A 65 LYS A 67
SITE 2 AC2 14 ILE A 104 LEU A 120 GLU A 121 VAL A 126
SITE 3 AC2 14 ASP A 128 GLU A 171 LEU A 174 ILE A 185
SITE 4 AC2 14 ASP A 186 HOH A 565
CRYST1 97.720 97.720 80.609 90.00 90.00 120.00 P 65 6
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 0.010233 0.005908 0.000000 0.00000
SCALE2 0.000000 0.011816 0.000000 0.00000
SCALE3 0.000000 0.000000 0.012406 0.00000
(ATOM LINES ARE NOT SHOWN.)
END
