HEADER APOPTOSIS 07-NOV-12 4HW4
TITLE DISCOVERY OF POTENT MCL-1 INHIBITORS USING FRAGMENT-BASED METHODS AND
TITLE 2 STRUCTURE-BASED DESIGN
COMPND MOL_ID: 1;
COMPND 2 MOLECULE: INDUCED MYELOID LEUKEMIA CELL DIFFERENTIATION PROTEIN MCL-
COMPND 3 1;
COMPND 4 CHAIN: A, B;
COMPND 5 SYNONYM: BCL-2-LIKE PROTEIN 3, BCL2-L-3, BCL-2-RELATED PROTEIN
COMPND 6 EAT/MCL1, MCL1/EAT;
COMPND 7 ENGINEERED: YES;
COMPND 8 MOL_ID: 2;
COMPND 9 MOLECULE: MCL-1 BH3 PEPTIDE;
COMPND 10 CHAIN: C, D;
COMPND 11 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: MCL1, BCL2L3;
SOURCE 6 EXPRESSION_SYSTEM: ESCHERICHIA COLI;
SOURCE 7 EXPRESSION_SYSTEM_TAXID: 562;
SOURCE 8 MOL_ID: 2;
SOURCE 9 SYNTHETIC: YES;
SOURCE 10 OTHER_DETAILS: SYNTHETIC PEPTIDE
KEYWDS ANTI-APOPTOTIC PROTEIN, BH3 PEPTIDES, APOPTOSIS
EXPDTA X-RAY DIFFRACTION
AUTHOR A.FRIBERG,B.ZHAO
REVDAT 2 06-MAR-13 4HW4 1 JRNL
REVDAT 1 09-JAN-13 4HW4 0
JRNL AUTH A.FRIBERG,D.VIGIL,B.ZHAO,R.N.DANIELS,J.P.BURKE,
JRNL AUTH 2 P.M.GARCIA-BARRANTES,D.CAMPER,B.A.CHAUDER,T.LEE,
JRNL AUTH 3 E.T.OLEJNICZAK,S.W.FESIK
JRNL TITL DISCOVERY OF POTENT MYELOID CELL LEUKEMIA 1 (MCL-1)
JRNL TITL 2 INHIBITORS USING FRAGMENT-BASED METHODS AND STRUCTURE-BASED
JRNL TITL 3 DESIGN.
JRNL REF J.MED.CHEM. V. 56 15 2013
JRNL REFN ISSN 0022-2623
JRNL PMID 23244564
JRNL DOI 10.1021/JM301448P
REMARK 2
REMARK 2 RESOLUTION. 1.53 ANGSTROMS.
REMARK 3
REMARK 3 REFINEMENT.
REMARK 3 PROGRAM : PHENIX (PHENIX.REFINE: 1.8_1069)
REMARK 3 AUTHORS : PAUL ADAMS,PAVEL AFONINE,VICENT CHEN,IAN
REMARK 3 : DAVIS,KRESHNA GOPAL,RALF GROSSE-
REMARK 3 : KUNSTLEVE,LI-WEI HUNG,ROBERT IMMORMINO,
REMARK 3 : TOM IOERGER,AIRLIE MCCOY,ERIK MCKEE,NIGEL
REMARK 3 : MORIARTY,REETAL PAI,RANDY READ,JANE
REMARK 3 : RICHARDSON,DAVID RICHARDSON,TOD ROMO,JIM
REMARK 3 : SACCHETTINI,NICHOLAS SAUTER,JACOB SMITH,
REMARK 3 : LAURENT STORONI,TOM TERWILLIGER,PETER
REMARK 3 : ZWART
REMARK 3
REMARK 3 REFINEMENT TARGET : ENGH & HUBER
REMARK 3
REMARK 3 DATA USED IN REFINEMENT.
REMARK 3 RESOLUTION RANGE HIGH (ANGSTROMS) : 1.53
REMARK 3 RESOLUTION RANGE LOW (ANGSTROMS) : 34.74
REMARK 3 MIN(FOBS/SIGMA_FOBS) : 1.380
REMARK 3 COMPLETENESS FOR RANGE (%) : 99.9
REMARK 3 NUMBER OF REFLECTIONS : 49292
REMARK 3
REMARK 3 FIT TO DATA USED IN REFINEMENT.
REMARK 3 R VALUE (WORKING + TEST SET) : 0.140
REMARK 3 R VALUE (WORKING SET) : 0.137
REMARK 3 FREE R VALUE : 0.184
REMARK 3 FREE R VALUE TEST SET SIZE (%) : 5.060
REMARK 3 FREE R VALUE TEST SET COUNT : 2495
REMARK 3
REMARK 3 FIT TO DATA USED IN REFINEMENT (IN BINS).
REMARK 3 BIN RESOLUTION RANGE COMPL. NWORK NFREE RWORK RFREE
REMARK 3 1 34.7534 - 4.0073 0.99 2684 144 0.1659 0.1674
REMARK 3 2 4.0073 - 3.1814 1.00 2640 133 0.1304 0.1641
REMARK 3 3 3.1814 - 2.7794 1.00 2614 128 0.1400 0.1686
REMARK 3 4 2.7794 - 2.5254 1.00 2601 152 0.1302 0.2016
REMARK 3 5 2.5254 - 2.3444 1.00 2625 144 0.1268 0.1754
REMARK 3 6 2.3444 - 2.2062 1.00 2582 143 0.1177 0.1754
REMARK 3 7 2.2062 - 2.0958 1.00 2597 116 0.1129 0.1888
REMARK 3 8 2.0958 - 2.0045 1.00 2604 142 0.1218 0.1893
REMARK 3 9 2.0045 - 1.9274 1.00 2587 140 0.1246 0.1833
REMARK 3 10 1.9274 - 1.8609 1.00 2552 157 0.1259 0.1949
REMARK 3 11 1.8609 - 1.8027 1.00 2625 149 0.1262 0.1954
REMARK 3 12 1.8027 - 1.7512 1.00 2580 148 0.1288 0.2188
REMARK 3 13 1.7512 - 1.7051 1.00 2570 124 0.1372 0.2051
REMARK 3 14 1.7051 - 1.6635 1.00 2568 144 0.1418 0.2038
REMARK 3 15 1.6635 - 1.6257 1.00 2597 135 0.1490 0.2328
REMARK 3 16 1.6257 - 1.5911 1.00 2627 131 0.1527 0.2340
REMARK 3 17 1.5911 - 1.5592 1.00 2542 133 0.1694 0.2471
REMARK 3 18 1.5592 - 1.5298 0.99 2602 132 0.1942 0.2524
REMARK 3
REMARK 3 BULK SOLVENT MODELLING.
REMARK 3 METHOD USED : FLAT BULK SOLVENT MODEL
REMARK 3 SOLVENT RADIUS : 1.11
REMARK 3 SHRINKAGE RADIUS : 0.90
REMARK 3 K_SOL : NULL
REMARK 3 B_SOL : NULL
REMARK 3
REMARK 3 ERROR ESTIMATES.
REMARK 3 COORDINATE ERROR (MAXIMUM-LIKELIHOOD BASED) : 0.140
REMARK 3 PHASE ERROR (DEGREES, MAXIMUM-LIKELIHOOD BASED) : 19.410
REMARK 3
REMARK 3 B VALUES.
REMARK 3 FROM WILSON PLOT (A**2) : NULL
REMARK 3 MEAN B VALUE (OVERALL, A**2) : NULL
REMARK 3 OVERALL ANISOTROPIC B VALUE.
REMARK 3 B11 (A**2) : NULL
REMARK 3 B22 (A**2) : NULL
REMARK 3 B33 (A**2) : NULL
REMARK 3 B12 (A**2) : NULL
REMARK 3 B13 (A**2) : NULL
REMARK 3 B23 (A**2) : NULL
REMARK 3
REMARK 3 TWINNING INFORMATION.
REMARK 3 FRACTION: NULL
REMARK 3 OPERATOR: NULL
REMARK 3
REMARK 3 DEVIATIONS FROM IDEAL VALUES.
REMARK 3 RMSD COUNT
REMARK 3 BOND : 0.008 2697
REMARK 3 ANGLE : 1.005 3621
REMARK 3 CHIRALITY : 0.053 404
REMARK 3 PLANARITY : 0.005 467
REMARK 3 DIHEDRAL : 13.175 1017
REMARK 3
REMARK 3 TLS DETAILS
REMARK 3 NUMBER OF TLS GROUPS : NULL
REMARK 3
REMARK 3 NCS DETAILS
REMARK 3 NUMBER OF NCS GROUPS : NULL
REMARK 3
REMARK 3 OTHER REFINEMENT REMARKS: NULL
REMARK 4
REMARK 4 4HW4 COMPLIES WITH FORMAT V. 3.30, 13-JUL-11
REMARK 100
REMARK 100 THIS ENTRY HAS BEEN PROCESSED BY RCSB ON 08-NOV-12.
REMARK 100 THE RCSB ID CODE IS RCSB075993.
REMARK 200
REMARK 200 EXPERIMENTAL DETAILS
REMARK 200 EXPERIMENT TYPE : X-RAY DIFFRACTION
REMARK 200 DATE OF DATA COLLECTION : 19-JUN-12
REMARK 200 TEMPERATURE (KELVIN) : 100
REMARK 200 PH : 5.5
REMARK 200 NUMBER OF CRYSTALS USED : 1
REMARK 200
REMARK 200 SYNCHROTRON (Y/N) : Y
REMARK 200 RADIATION SOURCE : APS
REMARK 200 BEAMLINE : 21-ID-G
REMARK 200 X-RAY GENERATOR MODEL : NULL
REMARK 200 MONOCHROMATIC OR LAUE (M/L) : M
REMARK 200 WAVELENGTH OR RANGE (A) : 0.97856
REMARK 200 MONOCHROMATOR : SAGITALLY FOCUSED SI(111)
REMARK 200 OPTICS : NULL
REMARK 200
REMARK 200 DETECTOR TYPE : CCD
REMARK 200 DETECTOR MANUFACTURER : MAR SCANNER 300 MM PLATE
REMARK 200 INTENSITY-INTEGRATION SOFTWARE : HKL-2000
REMARK 200 DATA SCALING SOFTWARE : HKL-2000
REMARK 200
REMARK 200 NUMBER OF UNIQUE REFLECTIONS : 49398
REMARK 200 RESOLUTION RANGE HIGH (A) : 1.530
REMARK 200 RESOLUTION RANGE LOW (A) : 50.000
REMARK 200 REJECTION CRITERIA (SIGMA(I)) : 1.000
REMARK 200
REMARK 200 OVERALL.
REMARK 200 COMPLETENESS FOR RANGE (%) : 100.0
REMARK 200 DATA REDUNDANCY : NULL
REMARK 200 R MERGE (I) : 0.04700
REMARK 200 R SYM (I) : 0.04200
REMARK 200 <I/SIGMA(I)> FOR THE DATA SET : NULL
REMARK 200
REMARK 200 IN THE HIGHEST RESOLUTION SHELL.
REMARK 200 HIGHEST RESOLUTION SHELL, RANGE HIGH (A) : 1.53
REMARK 200 HIGHEST RESOLUTION SHELL, RANGE LOW (A) : 1.56
REMARK 200 COMPLETENESS FOR SHELL (%) : 100.0
REMARK 200 DATA REDUNDANCY IN SHELL : 3.40
REMARK 200 R MERGE FOR SHELL (I) : 0.31300
REMARK 200 R SYM FOR SHELL (I) : 0.40800
REMARK 200 <I/SIGMA(I)> FOR SHELL : 2.460
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 (%): 41.15
REMARK 280 MATTHEWS COEFFICIENT, VM (ANGSTROMS**3/DA): 2.09
REMARK 280
REMARK 280 CRYSTALLIZATION CONDITIONS: 25% PEG3350, 0.2M NACL, 0.1M BIS-TRIS,
REMARK 280 PH 5.5, VAPOR DIFFUSION, HANGING DROP, 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 24.17650
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
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: 1830 ANGSTROM**2
REMARK 350 SURFACE AREA OF THE COMPLEX: 8650 ANGSTROM**2
REMARK 350 CHANGE IN SOLVENT FREE ENERGY: -13.0 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: 1830 ANGSTROM**2
REMARK 350 SURFACE AREA OF THE COMPLEX: 7830 ANGSTROM**2
REMARK 350 CHANGE IN SOLVENT FREE ENERGY: -12.0 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 GLU A 325
REMARK 465 GLY A 326
REMARK 465 GLY A 327
REMARK 465 ALA B 193
REMARK 465 LYS B 194
REMARK 465 ASP B 195
REMARK 465 THR B 196
REMARK 465 LYS B 197
REMARK 465 PRO B 198
REMARK 465 MET B 199
REMARK 465 GLY B 200
REMARK 465 ARG B 201
REMARK 465 SER B 202
REMARK 465 GLU B 322
REMARK 465 ASP B 323
REMARK 465 LEU B 324
REMARK 465 GLU B 325
REMARK 465 GLY B 326
REMARK 465 GLY B 327
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 322 CG CD OE1 OE2
REMARK 470 ASP A 323 CG OD1 OD2
REMARK 470 LEU A 324 CG CD1 CD2
REMARK 500
REMARK 500 GEOMETRY AND STEREOCHEMISTRY
REMARK 500 SUBTOPIC: CLOSE CONTACTS IN SAME ASYMMETRIC UNIT
REMARK 500
REMARK 500 THE FOLLOWING ATOMS ARE IN CLOSE CONTACT.
REMARK 500
REMARK 500 ATM1 RES C SSEQI ATM2 RES C SSEQI DISTANCE
REMARK 500 O ILE A 281 O HOH A 607 1.82
REMARK 500 O HOH A 437 O HOH A 607 1.88
REMARK 500 O HOH C 121 O HOH C 123 1.88
REMARK 500 O HOH A 571 O HOH B 485 1.88
REMARK 500 O HOH A 611 O HOH B 505 1.90
REMARK 500 O HOH A 597 O HOH A 600 1.93
REMARK 500 O HOH A 594 O HOH A 602 1.96
REMARK 500 O HOH A 606 O HOH A 609 1.97
REMARK 500 O HOH B 487 O HOH B 488 1.98
REMARK 500 O HOH B 517 O HOH D 113 1.99
REMARK 500 O HOH A 569 O HOH A 599 2.00
REMARK 500 O THR B 191 O HOH B 518 2.01
REMARK 500 O HOH A 591 O HOH A 600 2.03
REMARK 500 O HOH A 545 O HOH A 577 2.10
REMARK 500 O GLY B 203 O HOH B 492 2.14
REMARK 500 O HOH C 128 O HOH C 130 2.15
REMARK 500 C ASN A 282 O HOH A 607 2.15
REMARK 500 C THR B 191 O HOH B 518 2.17
REMARK 500 O HOH B 490 O HOH B 508 2.18
REMARK 500
REMARK 500 REMARK: NULL
REMARK 500
REMARK 500 GEOMETRY AND STEREOCHEMISTRY
REMARK 500 SUBTOPIC: CLOSE CONTACTS
REMARK 500
REMARK 500 THE FOLLOWING ATOMS THAT ARE RELATED BY CRYSTALLOGRAPHIC
REMARK 500 SYMMETRY ARE IN CLOSE CONTACT. AN ATOM LOCATED WITHIN 0.15
REMARK 500 ANGSTROMS OF A SYMMETRY RELATED ATOM IS ASSUMED TO BE ON A
REMARK 500 SPECIAL POSITION AND IS, THEREFORE, LISTED IN REMARK 375
REMARK 500 INSTEAD OF REMARK 500. ATOMS WITH NON-BLANK ALTERNATE
REMARK 500 LOCATION INDICATORS ARE NOT INCLUDED IN THE CALCULATIONS.
REMARK 500
REMARK 500 DISTANCE CUTOFF:
REMARK 500 2.2 ANGSTROMS FOR CONTACTS NOT INVOLVING HYDROGEN ATOMS
REMARK 500 1.6 ANGSTROMS FOR CONTACTS INVOLVING HYDROGEN ATOMS
REMARK 500
REMARK 500 ATM1 RES C SSEQI ATM2 RES C SSEQI SSYMOP DISTANCE
REMARK 500 O HOH B 515 O HOH D 124 2454 1.45
REMARK 500 O HOH A 575 O HOH C 116 2455 1.81
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 ARG A 300 -70.05 -124.53
REMARK 500 THR B 191 -114.07 -112.78
REMARK 500 ARG B 310 30.35 70.73
REMARK 500
REMARK 500 REMARK: NULL
REMARK 900
REMARK 900 RELATED ENTRIES
REMARK 900 RELATED ID: 4HW2 RELATED DB: PDB
REMARK 900 RELATED ID: 4HW3 RELATED DB: PDB
REMARK 900 RELATED ID: 4HW4 RELATED DB: PDB
DBREF 4HW4 A 172 327 UNP Q07820 MCL1_HUMAN 172 327
DBREF 4HW4 B 172 327 UNP Q07820 MCL1_HUMAN 172 327
DBREF 4HW4 C 0 17 PDB 4HW4 4HW4 0 17
DBREF 4HW4 D 0 17 PDB 4HW4 4HW4 0 17
SEQADV 4HW4 GLY A 171 UNP Q07820 EXPRESSION TAG
SEQADV 4HW4 GLY B 171 UNP Q07820 EXPRESSION TAG
SEQRES 1 A 157 GLY ASP GLU LEU TYR ARG GLN SER LEU GLU ILE ILE SER
SEQRES 2 A 157 ARG TYR LEU ARG GLU GLN ALA THR GLY ALA LYS ASP THR
SEQRES 3 A 157 LYS PRO MET GLY ARG SER GLY ALA THR SER ARG LYS ALA
SEQRES 4 A 157 LEU GLU THR LEU ARG ARG VAL GLY ASP GLY VAL GLN ARG
SEQRES 5 A 157 ASN HIS GLU THR ALA PHE GLN GLY MET LEU ARG LYS LEU
SEQRES 6 A 157 ASP ILE LYS ASN GLU ASP ASP VAL LYS SER LEU SER ARG
SEQRES 7 A 157 VAL MET ILE HIS VAL PHE SER ASP GLY VAL THR ASN TRP
SEQRES 8 A 157 GLY ARG ILE VAL THR LEU ILE SER PHE GLY ALA PHE VAL
SEQRES 9 A 157 ALA LYS HIS LEU LYS THR ILE ASN GLN GLU SER CYS ILE
SEQRES 10 A 157 GLU PRO LEU ALA GLU SER ILE THR ASP VAL LEU VAL ARG
SEQRES 11 A 157 THR LYS ARG ASP TRP LEU VAL LYS GLN ARG GLY TRP ASP
SEQRES 12 A 157 GLY PHE VAL GLU PHE PHE HIS VAL GLU ASP LEU GLU GLY
SEQRES 13 A 157 GLY
SEQRES 1 B 157 GLY ASP GLU LEU TYR ARG GLN SER LEU GLU ILE ILE SER
SEQRES 2 B 157 ARG TYR LEU ARG GLU GLN ALA THR GLY ALA LYS ASP THR
SEQRES 3 B 157 LYS PRO MET GLY ARG SER GLY ALA THR SER ARG LYS ALA
SEQRES 4 B 157 LEU GLU THR LEU ARG ARG VAL GLY ASP GLY VAL GLN ARG
SEQRES 5 B 157 ASN HIS GLU THR ALA PHE GLN GLY MET LEU ARG LYS LEU
SEQRES 6 B 157 ASP ILE LYS ASN GLU ASP ASP VAL LYS SER LEU SER ARG
SEQRES 7 B 157 VAL MET ILE HIS VAL PHE SER ASP GLY VAL THR ASN TRP
SEQRES 8 B 157 GLY ARG ILE VAL THR LEU ILE SER PHE GLY ALA PHE VAL
SEQRES 9 B 157 ALA LYS HIS LEU LYS THR ILE ASN GLN GLU SER CYS ILE
SEQRES 10 B 157 GLU PRO LEU ALA GLU SER ILE THR ASP VAL LEU VAL ARG
SEQRES 11 B 157 THR LYS ARG ASP TRP LEU VAL LYS GLN ARG GLY TRP ASP
SEQRES 12 B 157 GLY PHE VAL GLU PHE PHE HIS VAL GLU ASP LEU GLU GLY
SEQRES 13 B 157 GLY
SEQRES 1 C 18 ACE ALA LEU GLU THR LEU ARG ARG VAL GLY ASP GLY VAL
SEQRES 2 C 18 GLN ARG ASN HIS NH2
SEQRES 1 D 18 ACE ALA LEU GLU THR LEU ARG ARG VAL GLY ASP GLY VAL
SEQRES 2 D 18 GLN ARG ASN HIS NH2
HET ACE C 0 3
HET NH2 C 17 1
HET ACE D 0 3
HET NH2 D 17 1
HETNAM ACE ACETYL GROUP
HETNAM NH2 AMINO GROUP
FORMUL 3 ACE 2(C2 H4 O)
FORMUL 3 NH2 2(H2 N)
FORMUL 5 HOH *387(H2 O)
HELIX 1 1 ASP A 172 GLY A 192 1 21
HELIX 2 2 SER A 202 HIS A 224 1 23
HELIX 3 3 HIS A 224 ASP A 236 1 13
HELIX 4 4 ASN A 239 PHE A 254 1 16
HELIX 5 5 SER A 255 GLY A 257 5 3
HELIX 6 6 ASN A 260 ILE A 281 1 22
HELIX 7 7 GLN A 283 SER A 285 5 3
HELIX 8 8 CYS A 286 ARG A 300 1 15
HELIX 9 9 LYS A 302 GLN A 309 1 8
HELIX 10 10 ARG A 310 HIS A 320 1 11
HELIX 11 11 ASP B 172 THR B 191 1 20
HELIX 12 12 ALA B 204 HIS B 224 1 21
HELIX 13 13 HIS B 224 ASP B 236 1 13
HELIX 14 14 ASN B 239 PHE B 254 1 16
HELIX 15 15 SER B 255 GLY B 257 5 3
HELIX 16 16 ASN B 260 ILE B 281 1 22
HELIX 17 17 GLN B 283 SER B 285 5 3
HELIX 18 18 CYS B 286 LYS B 302 1 17
HELIX 19 19 LYS B 302 GLN B 309 1 8
HELIX 20 20 ARG B 310 PHE B 319 1 10
HELIX 21 21 ALA C 1 HIS C 16 1 16
HELIX 22 22 ALA D 1 HIS D 16 1 16
LINK C ACE C 0 N ALA C 1 1555 1555 1.35
LINK C HIS C 16 N NH2 C 17 1555 1555 1.34
LINK C ACE D 0 N ALA D 1 1555 1555 1.33
LINK C HIS D 16 N NH2 D 17 1555 1555 1.33
CRYST1 50.070 48.353 68.183 90.00 93.83 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 0.019972 0.000000 0.001335 0.00000
SCALE2 0.000000 0.020681 0.000000 0.00000
SCALE3 0.000000 0.000000 0.014699 0.00000
(ATOM LINES ARE NOT SHOWN.)
END
