HEADER HYDROLASE/HYDROLASE INHIBITOR 13-FEB-12 4DPI
TITLE BACE-1 IN COMPLEX WITH HEA-MACROCYCLIC INHIBITOR, MV078512
COMPND MOL_ID: 1;
COMPND 2 MOLECULE: BETA-SECRETASE 1;
COMPND 3 CHAIN: A;
COMPND 4 FRAGMENT: UNP RESIDUES 57-446;
COMPND 5 SYNONYM: ASPARTYL PROTEASE 2, ASP2, ASP 2, BETA-SITE AMYLOID
COMPND 6 PRECURSOR PROTEIN CLEAVING ENZYME 1, BETA-SITE APP CLEAVING ENZYME 1,
COMPND 7 MEMAPSIN-2, MEMBRANE-ASSOCIATED ASPARTIC PROTEASE 2;
COMPND 8 EC: 3.4.23.46;
COMPND 9 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: BACE1, BACE, KIAA1149;
SOURCE 6 EXPRESSION_SYSTEM: ESCHERICHIA COLI;
SOURCE 7 EXPRESSION_SYSTEM_TAXID: 562;
SOURCE 8 EXPRESSION_SYSTEM_STRAIN: BL21(DE3);
SOURCE 9 EXPRESSION_SYSTEM_VECTOR_TYPE: PLASMID;
SOURCE 10 EXPRESSION_SYSTEM_PLASMID: PET21
KEYWDS BACE1, ASP2, BACE, MACROCYCLE, HYDROLASE-HYDROLASE INHIBITOR COMPLEX
EXPDTA X-RAY DIFFRACTION
AUTHOR J.LINDBERG,N.BORKAKOTI,D.DERBYSHIRE
REVDAT 2 02-JAN-13 4DPI 1 JRNL
REVDAT 1 11-JUL-12 4DPI 0
JRNL AUTH V.SANDGREN,T.AGBACK,P.O.JOHANSSON,J.LINDBERG,I.KVARNSTROM,
JRNL AUTH 2 B.SAMUELSSON,O.BELDA,A.DAHLGREN
JRNL TITL HIGHLY POTENT MACROCYCLIC BACE-1 INHIBITORS INCORPORATING A
JRNL TITL 2 HYDROXYETHYLAMINE CORE: DESIGN, SYNTHESIS AND X-RAY CRYSTAL
JRNL TITL 3 STRUCTURES OF ENZYME INHIBITOR COMPLEXES.
JRNL REF BIOORG.MED.CHEM. V. 20 4377 2012
JRNL REFN ISSN 0968-0896
JRNL PMID 22698785
JRNL DOI 10.1016/J.BMC.2012.05.039
REMARK 2
REMARK 2 RESOLUTION. 1.90 ANGSTROMS.
REMARK 3
REMARK 3 REFINEMENT.
REMARK 3 PROGRAM : REFMAC 5.5.0109
REMARK 3 AUTHORS : MURSHUDOV,VAGIN,DODSON
REMARK 3
REMARK 3 REFINEMENT TARGET : MAXIMUM LIKELIHOOD
REMARK 3
REMARK 3 DATA USED IN REFINEMENT.
REMARK 3 RESOLUTION RANGE HIGH (ANGSTROMS) : 1.90
REMARK 3 RESOLUTION RANGE LOW (ANGSTROMS) : 44.03
REMARK 3 DATA CUTOFF (SIGMA(F)) : 0.000
REMARK 3 COMPLETENESS FOR RANGE (%) : 99.7
REMARK 3 NUMBER OF REFLECTIONS : 31372
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) : 0.174
REMARK 3 R VALUE (WORKING SET) : 0.172
REMARK 3 FREE R VALUE : 0.219
REMARK 3 FREE R VALUE TEST SET SIZE (%) : 5.000
REMARK 3 FREE R VALUE TEST SET COUNT : 1580
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) : 1.90
REMARK 3 BIN RESOLUTION RANGE LOW (A) : 1.95
REMARK 3 REFLECTION IN BIN (WORKING SET) : 2108
REMARK 3 BIN COMPLETENESS (WORKING+TEST) (%) : 95.49
REMARK 3 BIN R VALUE (WORKING SET) : 0.2370
REMARK 3 BIN FREE R VALUE SET COUNT : 94
REMARK 3 BIN FREE R VALUE : 0.3090
REMARK 3
REMARK 3 NUMBER OF NON-HYDROGEN ATOMS USED IN REFINEMENT.
REMARK 3 PROTEIN ATOMS : 2943
REMARK 3 NUCLEIC ACID ATOMS : 0
REMARK 3 HETEROGEN ATOMS : 41
REMARK 3 SOLVENT ATOMS : 185
REMARK 3
REMARK 3 B VALUES.
REMARK 3 FROM WILSON PLOT (A**2) : NULL
REMARK 3 MEAN B VALUE (OVERALL, A**2) : 18.22
REMARK 3 OVERALL ANISOTROPIC B VALUE.
REMARK 3 B11 (A**2) : -0.01000
REMARK 3 B22 (A**2) : 0.01000
REMARK 3 B33 (A**2) : 0.01000
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): 0.151
REMARK 3 ESU BASED ON FREE R VALUE (A): 0.142
REMARK 3 ESU BASED ON MAXIMUM LIKELIHOOD (A): 0.092
REMARK 3 ESU FOR B VALUES BASED ON MAXIMUM LIKELIHOOD (A**2): 6.745
REMARK 3
REMARK 3 CORRELATION COEFFICIENTS.
REMARK 3 CORRELATION COEFFICIENT FO-FC : 0.953
REMARK 3 CORRELATION COEFFICIENT FO-FC FREE : 0.923
REMARK 3
REMARK 3 RMS DEVIATIONS FROM IDEAL VALUES COUNT RMS WEIGHT
REMARK 3 BOND LENGTHS REFINED ATOMS (A): 3279 ; 0.025 ; 0.022
REMARK 3 BOND LENGTHS OTHERS (A): NULL ; NULL ; NULL
REMARK 3 BOND ANGLES REFINED ATOMS (DEGREES): 4505 ; 1.969 ; 1.976
REMARK 3 BOND ANGLES OTHERS (DEGREES): NULL ; NULL ; NULL
REMARK 3 TORSION ANGLES, PERIOD 1 (DEGREES): 424 ; 6.874 ; 5.000
REMARK 3 TORSION ANGLES, PERIOD 2 (DEGREES): 150 ;33.727 ;24.000
REMARK 3 TORSION ANGLES, PERIOD 3 (DEGREES): 524 ;15.112 ;15.000
REMARK 3 TORSION ANGLES, PERIOD 4 (DEGREES): 19 ;18.359 ;15.000
REMARK 3 CHIRAL-CENTER RESTRAINTS (A**3): 496 ; 0.168 ; 0.200
REMARK 3 GENERAL PLANES REFINED ATOMS (A): 2560 ; 0.011 ; 0.021
REMARK 3 GENERAL PLANES OTHERS (A): NULL ; NULL ; NULL
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): 1942 ; 1.334 ; 1.500
REMARK 3 MAIN-CHAIN BOND OTHER ATOMS (A**2): NULL ; NULL ; NULL
REMARK 3 MAIN-CHAIN ANGLE REFINED ATOMS (A**2): 3186 ; 2.263 ; 2.000
REMARK 3 SIDE-CHAIN BOND REFINED ATOMS (A**2): 1337 ; 3.469 ; 3.000
REMARK 3 SIDE-CHAIN ANGLE REFINED ATOMS (A**2): 1294 ; 5.439 ; 4.500
REMARK 3
REMARK 3 ANISOTROPIC THERMAL FACTOR RESTRAINTS. COUNT RMS WEIGHT
REMARK 3 RIGID-BOND RESTRAINTS (A**2): NULL ; NULL ; NULL
REMARK 3 SPHERICITY; FREE ATOMS (A**2): NULL ; NULL ; NULL
REMARK 3 SPHERICITY; BONDED ATOMS (A**2): NULL ; NULL ; NULL
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 : 1
REMARK 3
REMARK 3 TLS GROUP : 1
REMARK 3 NUMBER OF COMPONENTS GROUP : 1
REMARK 3 COMPONENTS C SSSEQI TO C SSSEQI
REMARK 3 RESIDUE RANGE : A 1 A 385
REMARK 3 ORIGIN FOR THE GROUP (A): 2.2463 1.5409 14.9754
REMARK 3 T TENSOR
REMARK 3 T11: 0.0125 T22: 0.0244
REMARK 3 T33: 0.0342 T12: 0.0021
REMARK 3 T13: -0.0069 T23: 0.0015
REMARK 3 L TENSOR
REMARK 3 L11: 0.0662 L22: 0.3460
REMARK 3 L33: 0.6589 L12: 0.1379
REMARK 3 L13: -0.0666 L23: -0.0029
REMARK 3 S TENSOR
REMARK 3 S11: 0.0073 S12: -0.0106 S13: -0.0108
REMARK 3 S21: -0.0089 S22: 0.0063 S23: -0.0049
REMARK 3 S31: 0.0045 S32: 0.0487 S33: -0.0136
REMARK 3
REMARK 3 BULK SOLVENT MODELLING.
REMARK 3 METHOD USED : MASK
REMARK 3 PARAMETERS FOR MASK CALCULATION
REMARK 3 VDW PROBE RADIUS : 1.40
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
REMARK 4
REMARK 4 4DPI COMPLIES WITH FORMAT V. 3.30, 13-JUL-11
REMARK 100
REMARK 100 THIS ENTRY HAS BEEN PROCESSED BY RCSB ON 14-FEB-12.
REMARK 100 THE RCSB ID CODE IS RCSB070621.
REMARK 200
REMARK 200 EXPERIMENTAL DETAILS
REMARK 200 EXPERIMENT TYPE : X-RAY DIFFRACTION
REMARK 200 DATE OF DATA COLLECTION : 29-JUN-11
REMARK 200 TEMPERATURE (KELVIN) : 100
REMARK 200 PH : 4.5
REMARK 200 NUMBER OF CRYSTALS USED : 1
REMARK 200
REMARK 200 SYNCHROTRON (Y/N) : Y
REMARK 200 RADIATION SOURCE : ESRF
REMARK 200 BEAMLINE : ID23-2
REMARK 200 X-RAY GENERATOR MODEL : NULL
REMARK 200 MONOCHROMATIC OR LAUE (M/L) : M
REMARK 200 WAVELENGTH OR RANGE (A) : 0.976
REMARK 200 MONOCHROMATOR : GRAPHITE
REMARK 200 OPTICS : MIRRORS
REMARK 200
REMARK 200 DETECTOR TYPE : CCD
REMARK 200 DETECTOR MANUFACTURER : ADSC QUANTUM 315R
REMARK 200 INTENSITY-INTEGRATION SOFTWARE : MOSFLM
REMARK 200 DATA SCALING SOFTWARE : SCALA
REMARK 200
REMARK 200 NUMBER OF UNIQUE REFLECTIONS : 31429
REMARK 200 RESOLUTION RANGE HIGH (A) : 1.900
REMARK 200 RESOLUTION RANGE LOW (A) : 61.843
REMARK 200 REJECTION CRITERIA (SIGMA(I)) : 2.000
REMARK 200
REMARK 200 OVERALL.
REMARK 200 COMPLETENESS FOR RANGE (%) : 99.7
REMARK 200 DATA REDUNDANCY : 4.600
REMARK 200 R MERGE (I) : NULL
REMARK 200 R SYM (I) : 0.07900
REMARK 200 <I/SIGMA(I)> FOR THE DATA SET : 13.5000
REMARK 200
REMARK 200 IN THE HIGHEST RESOLUTION SHELL.
REMARK 200 HIGHEST RESOLUTION SHELL, RANGE HIGH (A) : 1.90
REMARK 200 HIGHEST RESOLUTION SHELL, RANGE LOW (A) : 2.00
REMARK 200 COMPLETENESS FOR SHELL (%) : 97.9
REMARK 200 DATA REDUNDANCY IN SHELL : 4.10
REMARK 200 R MERGE FOR SHELL (I) : 0.24100
REMARK 200 R SYM FOR SHELL (I) : 0.24100
REMARK 200 <I/SIGMA(I)> FOR SHELL : 2.900
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 (%): 43.63
REMARK 280 MATTHEWS COEFFICIENT, VM (ANGSTROMS**3/DA): 2.18
REMARK 280
REMARK 280 CRYSTALLIZATION CONDITIONS: 18% PEG 1000, 0.1 NA-ACETATE PH4.5, 5%
REMARK 280 GLYCEROL, VAPOR DIFFUSION, TEMPERATURE 291K
REMARK 290
REMARK 290 CRYSTALLOGRAPHIC SYMMETRY
REMARK 290 SYMMETRY OPERATORS FOR SPACE GROUP: P 21 21 21
REMARK 290
REMARK 290 SYMOP SYMMETRY
REMARK 290 NNNMMM OPERATOR
REMARK 290 1555 X,Y,Z
REMARK 290 2555 -X+1/2,-Y,Z+1/2
REMARK 290 3555 -X,Y+1/2,-Z+1/2
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 24.30000
REMARK 290 SMTRY2 2 0.000000 -1.000000 0.000000 0.00000
REMARK 290 SMTRY3 2 0.000000 0.000000 1.000000 52.00000
REMARK 290 SMTRY1 3 -1.000000 0.000000 0.000000 0.00000
REMARK 290 SMTRY2 3 0.000000 1.000000 0.000000 38.46000
REMARK 290 SMTRY3 3 0.000000 0.000000 -1.000000 52.00000
REMARK 290 SMTRY1 4 1.000000 0.000000 0.000000 24.30000
REMARK 290 SMTRY2 4 0.000000 -1.000000 0.000000 38.46000
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 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 MET A 43
REMARK 465 ARG A 44
REMARK 465 GLY A 45
REMARK 465 SER A 46
REMARK 465 ALA A 205
REMARK 465 GLY A 206
REMARK 465 PHE A 207
REMARK 465 PRO A 208
REMARK 465 LEU A 209
REMARK 465 ASN A 210
REMARK 465 GLN A 211
REMARK 465 SER A 212
REMARK 465 GLU A 213
REMARK 465 VAL A 214
REMARK 465 LEU A 215
REMARK 465 ALA A 216
REMARK 465 SER A 217
REMARK 465 VAL A 409
REMARK 500
REMARK 500 GEOMETRY AND STEREOCHEMISTRY
REMARK 500 SUBTOPIC: COVALENT BOND ANGLES
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,A3,1X,A1,I4,A1,3(1X,A4,2X),12X,F5.1)
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 ATM2 ATM3
REMARK 500 ARG A 98 NE - CZ - NH1 ANGL. DEV. = -3.2 DEGREES
REMARK 500 VAL A 404 CG1 - CB - CG2 ANGL. DEV. = 10.5 DEGREES
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 PHE A 156 -65.40 -107.87
REMARK 500 TRP A 245 -85.34 -145.17
REMARK 500 ALA A 320 128.23 -37.23
REMARK 500 ASN A 341 14.94 56.04
REMARK 500 ALA A 371 34.74 -97.72
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 0N1 A 501
REMARK 900
REMARK 900 RELATED ENTRIES
REMARK 900 RELATED ID: 4DPF RELATED DB: PDB
DBREF 4DPI A 44 433 UNP P56817 BACE1_HUMAN 57 446
SEQADV 4DPI MET A 43 UNP P56817 INITIATING METHIONINE
SEQRES 1 A 391 MET ARG GLY SER PHE VAL GLU MET VAL ASP ASN LEU ARG
SEQRES 2 A 391 GLY LYS SER GLY GLN GLY TYR TYR VAL GLU MET THR VAL
SEQRES 3 A 391 GLY SER PRO PRO GLN THR LEU ASN ILE LEU VAL ASP THR
SEQRES 4 A 391 GLY SER SER ASN PHE ALA VAL GLY ALA ALA PRO HIS PRO
SEQRES 5 A 391 PHE LEU HIS ARG TYR TYR GLN ARG GLN LEU SER SER THR
SEQRES 6 A 391 TYR ARG ASP LEU ARG LYS GLY VAL TYR VAL PRO TYR THR
SEQRES 7 A 391 GLN GLY LYS TRP GLU GLY GLU LEU GLY THR ASP LEU VAL
SEQRES 8 A 391 SER ILE PRO HIS GLY PRO ASN VAL THR VAL ARG ALA ASN
SEQRES 9 A 391 ILE ALA ALA ILE THR GLU SER ASP LYS PHE PHE ILE ASN
SEQRES 10 A 391 GLY SER ASN TRP GLU GLY ILE LEU GLY LEU ALA TYR ALA
SEQRES 11 A 391 GLU ILE ALA ARG PRO ASP ASP SER LEU GLU PRO PHE PHE
SEQRES 12 A 391 ASP SER LEU VAL LYS GLN THR HIS VAL PRO ASN LEU PHE
SEQRES 13 A 391 SER LEU GLN LEU CYS GLY ALA GLY PHE PRO LEU ASN GLN
SEQRES 14 A 391 SER GLU VAL LEU ALA SER VAL GLY GLY SER MET ILE ILE
SEQRES 15 A 391 GLY GLY ILE ASP HIS SER LEU TYR THR GLY SER LEU TRP
SEQRES 16 A 391 TYR THR PRO ILE ARG ARG GLU TRP TYR TYR GLU VAL ILE
SEQRES 17 A 391 ILE VAL ARG VAL GLU ILE ASN GLY GLN ASP LEU LYS MET
SEQRES 18 A 391 ASP CYS LYS GLU TYR ASN TYR ASP LYS SER ILE VAL ASP
SEQRES 19 A 391 SER GLY THR THR ASN LEU ARG LEU PRO LYS LYS VAL PHE
SEQRES 20 A 391 GLU ALA ALA VAL LYS SER ILE LYS ALA ALA SER SER THR
SEQRES 21 A 391 GLU LYS PHE PRO ASP GLY PHE TRP LEU GLY GLU GLN LEU
SEQRES 22 A 391 VAL CYS TRP GLN ALA GLY THR THR PRO TRP ASN ILE PHE
SEQRES 23 A 391 PRO VAL ILE SER LEU TYR LEU MET GLY GLU VAL THR ASN
SEQRES 24 A 391 GLN SER PHE ARG ILE THR ILE LEU PRO GLN GLN TYR LEU
SEQRES 25 A 391 ARG PRO VAL GLU ASP VAL ALA THR SER GLN ASP ASP CYS
SEQRES 26 A 391 TYR LYS PHE ALA ILE SER GLN SER SER THR GLY THR VAL
SEQRES 27 A 391 MET GLY ALA VAL ILE MET GLU GLY PHE TYR VAL VAL PHE
SEQRES 28 A 391 ASP ARG ALA ARG LYS ARG ILE GLY PHE ALA VAL SER ALA
SEQRES 29 A 391 CYS HIS VAL HIS ASP GLU PHE ARG THR ALA ALA VAL GLU
SEQRES 30 A 391 GLY PRO PHE VAL THR LEU ASP MET GLU ASP CYS GLY TYR
SEQRES 31 A 391 ASN
HET 0N1 A 501 82
HETNAM 0N1 (4S,8E,11R)-4-[(1R)-1-HYDROXY-2-{[3-(PROPAN-2-YL)
HETNAM 2 0N1 BENZYL]AMINO}ETHYL]-16-METHYL-11-PHENYL-6-OXA-3,12-
HETNAM 3 0N1 DIAZABICYCLO[12.3.1]OCTADECA-1(18),8,14,16-TETRAENE-2,
HETNAM 4 0N1 13-DIONE
FORMUL 2 0N1 C34 H41 N3 O4
FORMUL 3 HOH *185(H2 O)
HELIX 1 1 PHE A 47 VAL A 51 5 5
HELIX 2 2 GLN A 101 SER A 105 5 5
HELIX 3 3 TYR A 171 ALA A 175 5 5
HELIX 4 4 PRO A 183 THR A 192 1 10
HELIX 5 5 ASP A 228 SER A 230 5 3
HELIX 6 6 ASP A 264 TYR A 270 5 7
HELIX 7 7 LYS A 286 SER A 300 1 15
HELIX 8 8 PRO A 306 LEU A 311 1 6
HELIX 9 9 PRO A 324 PHE A 328 5 5
HELIX 10 10 LEU A 349 TYR A 353 1 5
HELIX 11 11 ASP A 359 SER A 363 5 5
HELIX 12 12 GLY A 382 GLU A 387 1 6
HELIX 13 13 ARG A 395 ARG A 397 5 3
SHEET 1 A 9 ARG A 109 PRO A 118 0
SHEET 2 A 9 LYS A 123 SER A 134 -1 O LEU A 128 N LYS A 113
SHEET 3 A 9 GLY A 61 VAL A 68 -1 N THR A 67 O SER A 134
SHEET 4 A 9 LEU A 54 LYS A 57 -1 N ARG A 55 O TYR A 63
SHEET 5 A 9 GLY A 219 ILE A 224 -1 O GLY A 220 N LEU A 54
SHEET 6 A 9 PHE A 198 CYS A 203 -1 N GLN A 201 O SER A 221
SHEET 7 A 9 PHE A 389 ASP A 394 -1 O PHE A 393 N PHE A 198
SHEET 8 A 9 ARG A 399 SER A 405 -1 O GLY A 401 N VAL A 392
SHEET 9 A 9 TYR A 232 PRO A 240 -1 N THR A 239 O ILE A 400
SHEET 1 B13 ARG A 109 PRO A 118 0
SHEET 2 B13 LYS A 123 SER A 134 -1 O LEU A 128 N LYS A 113
SHEET 3 B13 THR A 142 ASP A 154 -1 O ALA A 149 N GLU A 127
SHEET 4 B13 PHE A 86 GLY A 89 1 N VAL A 88 O ILE A 150
SHEET 5 B13 GLY A 165 GLY A 168 -1 O ILE A 166 N ALA A 87
SHEET 6 B13 GLN A 73 ASP A 80 1 N LEU A 78 O LEU A 167
SHEET 7 B13 GLY A 61 VAL A 68 -1 N VAL A 64 O ILE A 77
SHEET 8 B13 LEU A 54 LYS A 57 -1 N ARG A 55 O TYR A 63
SHEET 9 B13 GLY A 219 ILE A 224 -1 O GLY A 220 N LEU A 54
SHEET 10 B13 PHE A 198 CYS A 203 -1 N GLN A 201 O SER A 221
SHEET 11 B13 PHE A 389 ASP A 394 -1 O PHE A 393 N PHE A 198
SHEET 12 B13 ARG A 399 SER A 405 -1 O GLY A 401 N VAL A 392
SHEET 13 B13 TYR A 232 PRO A 240 -1 N THR A 239 O ILE A 400
SHEET 1 C 5 GLU A 248 VAL A 249 0
SHEET 2 C 5 SER A 273 VAL A 275 -1 O SER A 273 N VAL A 249
SHEET 3 C 5 THR A 379 MET A 381 1 O MET A 381 N ILE A 274
SHEET 4 C 5 LEU A 282 PRO A 285 -1 N ARG A 283 O VAL A 380
SHEET 5 C 5 ILE A 372 SER A 375 1 O SER A 373 N LEU A 284
SHEET 1 D 5 GLN A 259 ASP A 260 0
SHEET 2 D 5 ILE A 251 ILE A 256 -1 N ILE A 256 O GLN A 259
SHEET 3 D 5 ILE A 331 MET A 336 -1 O TYR A 334 N ARG A 253
SHEET 4 D 5 GLN A 342 ILE A 348 -1 O ILE A 348 N ILE A 331
SHEET 5 D 5 ALA A 417 VAL A 423 -1 O GLU A 419 N ARG A 345
SHEET 1 E 3 VAL A 316 GLN A 319 0
SHEET 2 E 3 ASP A 365 PHE A 370 -1 O ASP A 366 N TRP A 318
SHEET 3 E 3 LEU A 354 PRO A 356 -1 N ARG A 355 O LYS A 369
SSBOND 1 CYS A 203 CYS A 407 1555 1555 2.18
SSBOND 2 CYS A 265 CYS A 430 1555 1555 2.10
SSBOND 3 CYS A 317 CYS A 367 1555 1555 2.10
CISPEP 1 SER A 70 PRO A 71 0 -1.20
CISPEP 2 ARG A 176 PRO A 177 0 3.14
CISPEP 3 TYR A 270 ASP A 271 0 0.83
CISPEP 4 GLY A 420 PRO A 421 0 -0.16
SITE 1 AC1 23 GLY A 59 GLN A 60 GLY A 61 LEU A 78
SITE 2 AC1 23 ASP A 80 GLY A 82 SER A 83 VAL A 117
SITE 3 AC1 23 PRO A 118 TYR A 119 THR A 120 GLN A 121
SITE 4 AC1 23 ILE A 158 ARG A 176 TYR A 246 ASP A 276
SITE 5 AC1 23 SER A 277 GLY A 278 THR A 279 THR A 280
SITE 6 AC1 23 ARG A 283 ALA A 383 HOH A 624
CRYST1 48.600 76.920 104.000 90.00 90.00 90.00 P 21 21 21 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 0.020576 0.000000 0.000000 0.00000
SCALE2 0.000000 0.013001 0.000000 0.00000
SCALE3 0.000000 0.000000 0.009615 0.00000
(ATOM LINES ARE NOT SHOWN.)
END