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Database: PDB
Entry: 4FRI
LinkDB: 4FRI
Original site: 4FRI 
HEADER    HYDROLASE/INHIBITOR                     26-JUN-12   4FRI              
TITLE     CRYSTAL STRUCTURE OF BACE1 IN COMPLEX WITH BIARYLSPIRO AMINOOXAZOLINE 
TITLE    2 6                                                                    
COMPND    MOL_ID: 1;                                                            
COMPND   2 MOLECULE: BETA-SECRETASE 1;                                          
COMPND   3 CHAIN: A;                                                            
COMPND   4 FRAGMENT: CATALYTIC DOMAIN, UNP RESIDUES 43-453;                     
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;                                                     
COMPND  10 MUTATION: YES                                                        
SOURCE    MOL_ID: 1;                                                            
SOURCE   2 ORGANISM_SCIENTIFIC: HOMO SAPIENS;                                   
SOURCE   3 ORGANISM_COMMON: HUMAN;                                              
SOURCE   4 ORGANISM_TAXID: 9606;                                                
SOURCE   5 GENE: BACE, BACE1, KIAA1149;                                         
SOURCE   6 EXPRESSION_SYSTEM: ESCHERICHIA COLI;                                 
SOURCE   7 EXPRESSION_SYSTEM_TAXID: 562                                         
KEYWDS    MEMBRANE PROTEIN, ALZHEIMER'S DISEASE, ASPARTIC PROTEASE, HYDROLASE-  
KEYWDS   2 INHIBITOR COMPLEX                                                    
EXPDTA    X-RAY DIFFRACTION                                                     
AUTHOR    D.A.WHITTINGTON,A.M.LONG                                              
REVDAT   3   13-SEP-23 4FRI    1       REMARK SEQADV                            
REVDAT   2   12-DEC-12 4FRI    1       JRNL                                     
REVDAT   1   12-SEP-12 4FRI    0                                                
JRNL        AUTH   H.HUANG,D.S.LA,A.C.CHENG,D.A.WHITTINGTON,V.F.PATEL,K.CHEN,   
JRNL        AUTH 2 T.A.DINEEN,O.EPSTEIN,R.GRACEFFA,D.HICKMAN,Y.H.KIANG,S.LOUIE, 
JRNL        AUTH 3 Y.LUO,R.C.WAHL,P.H.WEN,S.WOOD,R.T.FREMEAU                    
JRNL        TITL   STRUCTURE- AND PROPERTY-BASED DESIGN OF AMINOOXAZOLINE       
JRNL        TITL 2 XANTHENES AS SELECTIVE, ORALLY EFFICACIOUS, AND CNS          
JRNL        TITL 3 PENETRABLE BACE INHIBITORS FOR THE TREATMENT OF ALZHEIMER'S  
JRNL        TITL 4 DISEASE.                                                     
JRNL        REF    J.MED.CHEM.                   V.  55  9156 2012              
JRNL        REFN                   ISSN 0022-2623                               
JRNL        PMID   22928914                                                     
JRNL        DOI    10.1021/JM300598E                                            
REMARK   2                                                                      
REMARK   2 RESOLUTION.    2.30 ANGSTROMS.                                       
REMARK   3                                                                      
REMARK   3 REFINEMENT.                                                          
REMARK   3   PROGRAM     : REFMAC                                               
REMARK   3   AUTHORS     : MURSHUDOV,SKUBAK,LEBEDEV,PANNU,STEINER,              
REMARK   3               : NICHOLLS,WINN,LONG,VAGIN                             
REMARK   3                                                                      
REMARK   3    REFINEMENT TARGET : MAXIMUM LIKELIHOOD                            
REMARK   3                                                                      
REMARK   3  DATA USED IN REFINEMENT.                                            
REMARK   3   RESOLUTION RANGE HIGH (ANGSTROMS) : 2.30                           
REMARK   3   RESOLUTION RANGE LOW  (ANGSTROMS) : 30.00                          
REMARK   3   DATA CUTOFF            (SIGMA(F)) : 0.000                          
REMARK   3   COMPLETENESS FOR RANGE        (%) : 96.9                           
REMARK   3   NUMBER OF REFLECTIONS             : 23045                          
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) : 0.201                           
REMARK   3   R VALUE            (WORKING SET) : 0.197                           
REMARK   3   FREE R VALUE                     : 0.246                           
REMARK   3   FREE R VALUE TEST SET SIZE   (%) : 7.300                           
REMARK   3   FREE R VALUE TEST SET COUNT      : 1676                            
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) : 2.30                         
REMARK   3   BIN RESOLUTION RANGE LOW        (A) : 2.36                         
REMARK   3   REFLECTION IN BIN     (WORKING SET) : 1350                         
REMARK   3   BIN COMPLETENESS (WORKING+TEST) (%) : 93.74                        
REMARK   3   BIN R VALUE           (WORKING SET) : 0.3760                       
REMARK   3   BIN FREE R VALUE SET COUNT          : 103                          
REMARK   3   BIN FREE R VALUE                    : 0.3960                       
REMARK   3                                                                      
REMARK   3  NUMBER OF NON-HYDROGEN ATOMS USED IN REFINEMENT.                    
REMARK   3   PROTEIN ATOMS            : 2931                                    
REMARK   3   NUCLEIC ACID ATOMS       : 0                                       
REMARK   3   HETEROGEN ATOMS          : 34                                      
REMARK   3   SOLVENT ATOMS            : 213                                     
REMARK   3                                                                      
REMARK   3  B VALUES.                                                           
REMARK   3   FROM WILSON PLOT           (A**2) : 48.10                          
REMARK   3   MEAN B VALUE      (OVERALL, A**2) : 38.73                          
REMARK   3   OVERALL ANISOTROPIC B VALUE.                                       
REMARK   3    B11 (A**2) : 0.09000                                              
REMARK   3    B22 (A**2) : 0.09000                                              
REMARK   3    B33 (A**2) : -0.14000                                             
REMARK   3    B12 (A**2) : 0.05000                                              
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): 0.285         
REMARK   3   ESU BASED ON FREE R VALUE                       (A): 0.226         
REMARK   3   ESU BASED ON MAXIMUM LIKELIHOOD                 (A): 0.147         
REMARK   3   ESU FOR B VALUES BASED ON MAXIMUM LIKELIHOOD (A**2): 6.043         
REMARK   3                                                                      
REMARK   3 CORRELATION COEFFICIENTS.                                            
REMARK   3   CORRELATION COEFFICIENT FO-FC      : 0.951                         
REMARK   3   CORRELATION COEFFICIENT FO-FC FREE : 0.928                         
REMARK   3                                                                      
REMARK   3  RMS DEVIATIONS FROM IDEAL VALUES        COUNT    RMS    WEIGHT      
REMARK   3   BOND LENGTHS REFINED ATOMS        (A):  3041 ; 0.008 ; 0.020       
REMARK   3   BOND LENGTHS OTHERS               (A):  2038 ; 0.001 ; 0.020       
REMARK   3   BOND ANGLES REFINED ATOMS   (DEGREES):  4134 ; 1.233 ; 1.957       
REMARK   3   BOND ANGLES OTHERS          (DEGREES):  4918 ; 0.821 ; 3.004       
REMARK   3   TORSION ANGLES, PERIOD 1    (DEGREES):   369 ; 6.628 ; 5.000       
REMARK   3   TORSION ANGLES, PERIOD 2    (DEGREES):   138 ;33.725 ;23.768       
REMARK   3   TORSION ANGLES, PERIOD 3    (DEGREES):   480 ;13.772 ;15.000       
REMARK   3   TORSION ANGLES, PERIOD 4    (DEGREES):    17 ;17.018 ;15.000       
REMARK   3   CHIRAL-CENTER RESTRAINTS       (A**3):   447 ; 0.069 ; 0.200       
REMARK   3   GENERAL PLANES REFINED ATOMS      (A):  3388 ; 0.004 ; 0.021       
REMARK   3   GENERAL PLANES OTHERS             (A):   649 ; 0.001 ; 0.020       
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):  NULL ;  NULL ;  NULL       
REMARK   3   MAIN-CHAIN BOND OTHER ATOMS    (A**2):  NULL ;  NULL ;  NULL       
REMARK   3   MAIN-CHAIN ANGLE REFINED ATOMS (A**2):  NULL ;  NULL ;  NULL       
REMARK   3   MAIN-CHAIN ANGLE OTHER ATOMS   (A**2):  NULL ;  NULL ;  NULL       
REMARK   3   SIDE-CHAIN BOND REFINED ATOMS  (A**2):  NULL ;  NULL ;  NULL       
REMARK   3   SIDE-CHAIN BOND OTHER ATOMS    (A**2):  NULL ;  NULL ;  NULL       
REMARK   3   SIDE-CHAIN ANGLE REFINED ATOMS (A**2):  NULL ;  NULL ;  NULL       
REMARK   3   SIDE-CHAIN ANGLE OTHER ATOMS   (A**2):  NULL ;  NULL ;  NULL       
REMARK   3   LONG RANGE B REFINED ATOMS     (A**2):  NULL ;  NULL ;  NULL       
REMARK   3   LONG RANGE B OTHER ATOMS       (A**2):  NULL ;  NULL ;  NULL       
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  : NULL                                       
REMARK   3                                                                      
REMARK   3  BULK SOLVENT MODELLING.                                             
REMARK   3   METHOD USED : MASK                                                 
REMARK   3   PARAMETERS FOR MASK CALCULATION                                    
REMARK   3   VDW PROBE RADIUS   : 1.20                                          
REMARK   3   ION PROBE RADIUS   : 0.80                                          
REMARK   3   SHRINKAGE RADIUS   : 0.80                                          
REMARK   3                                                                      
REMARK   3  OTHER REFINEMENT REMARKS: NULL                                      
REMARK   4                                                                      
REMARK   4 4FRI COMPLIES WITH FORMAT V. 3.30, 13-JUL-11                         
REMARK 100                                                                      
REMARK 100 THIS ENTRY HAS BEEN PROCESSED BY RCSB ON 03-JUL-12.                  
REMARK 100 THE DEPOSITION ID IS D_1000073264.                                   
REMARK 200                                                                      
REMARK 200 EXPERIMENTAL DETAILS                                                 
REMARK 200  EXPERIMENT TYPE                : X-RAY DIFFRACTION                  
REMARK 200  DATE OF DATA COLLECTION        : 22-FEB-08                          
REMARK 200  TEMPERATURE           (KELVIN) : 100                                
REMARK 200  PH                             : 6.6                                
REMARK 200  NUMBER OF CRYSTALS USED        : 1                                  
REMARK 200                                                                      
REMARK 200  SYNCHROTRON              (Y/N) : N                                  
REMARK 200  RADIATION SOURCE               : ROTATING ANODE                     
REMARK 200  BEAMLINE                       : NULL                               
REMARK 200  X-RAY GENERATOR MODEL          : RIGAKU FR-E SUPERBRIGHT            
REMARK 200  MONOCHROMATIC OR LAUE    (M/L) : M                                  
REMARK 200  WAVELENGTH OR RANGE        (A) : 1.5418                             
REMARK 200  MONOCHROMATOR                  : NULL                               
REMARK 200  OPTICS                         : VARIMAX HR                         
REMARK 200                                                                      
REMARK 200  DETECTOR TYPE                  : IMAGE PLATE                        
REMARK 200  DETECTOR MANUFACTURER          : RIGAKU RAXIS IV++                  
REMARK 200  INTENSITY-INTEGRATION SOFTWARE : DENZO                              
REMARK 200  DATA SCALING SOFTWARE          : SCALEPACK                          
REMARK 200                                                                      
REMARK 200  NUMBER OF UNIQUE REFLECTIONS   : 23047                              
REMARK 200  RESOLUTION RANGE HIGH      (A) : 2.300                              
REMARK 200  RESOLUTION RANGE LOW       (A) : 30.000                             
REMARK 200  REJECTION CRITERIA  (SIGMA(I)) : -3.000                             
REMARK 200                                                                      
REMARK 200 OVERALL.                                                             
REMARK 200  COMPLETENESS FOR RANGE     (%) : 96.7                               
REMARK 200  DATA REDUNDANCY                : 10.20                              
REMARK 200  R MERGE                    (I) : 0.14300                            
REMARK 200  R SYM                      (I) : NULL                               
REMARK 200  <I/SIGMA(I)> FOR THE DATA SET  : 7.6000                             
REMARK 200                                                                      
REMARK 200 IN THE HIGHEST RESOLUTION SHELL.                                     
REMARK 200  HIGHEST RESOLUTION SHELL, RANGE HIGH (A) : 2.30                     
REMARK 200  HIGHEST RESOLUTION SHELL, RANGE LOW  (A) : 2.38                     
REMARK 200  COMPLETENESS FOR SHELL     (%) : 94.3                               
REMARK 200  DATA REDUNDANCY IN SHELL       : 8.80                               
REMARK 200  R MERGE FOR SHELL          (I) : 0.91600                            
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: AMORE                                                 
REMARK 200 STARTING MODEL: 1W50                                                 
REMARK 200                                                                      
REMARK 200 REMARK: NULL                                                         
REMARK 280                                                                      
REMARK 280 CRYSTAL                                                              
REMARK 280 SOLVENT CONTENT, VS   (%): 55.50                                     
REMARK 280 MATTHEWS COEFFICIENT, VM (ANGSTROMS**3/DA): 2.76                     
REMARK 280                                                                      
REMARK 280 CRYSTALLIZATION CONDITIONS: 20% PEG 5000 MONOMETHYL ETHER, 200 MM    
REMARK 280  AMMONIUM IODIDE, 180 MM SODIUM CITRATE (PH 6.6), VAPOR DIFFUSION,   
REMARK 280  HANGING DROP, TEMPERATURE 293K                                      
REMARK 290                                                                      
REMARK 290 CRYSTALLOGRAPHIC SYMMETRY                                            
REMARK 290 SYMMETRY OPERATORS FOR SPACE GROUP: P 61 2 2                         
REMARK 290                                                                      
REMARK 290      SYMOP   SYMMETRY                                                
REMARK 290     NNNMMM   OPERATOR                                                
REMARK 290       1555   X,Y,Z                                                   
REMARK 290       2555   -Y,X-Y,Z+1/3                                            
REMARK 290       3555   -X+Y,-X,Z+2/3                                           
REMARK 290       4555   -X,-Y,Z+1/2                                             
REMARK 290       5555   Y,-X+Y,Z+5/6                                            
REMARK 290       6555   X-Y,X,Z+1/6                                             
REMARK 290       7555   Y,X,-Z+1/3                                              
REMARK 290       8555   X-Y,-Y,-Z                                               
REMARK 290       9555   -X,-X+Y,-Z+2/3                                          
REMARK 290      10555   -Y,-X,-Z+5/6                                            
REMARK 290      11555   -X+Y,Y,-Z+1/2                                           
REMARK 290      12555   X,X-Y,-Z+1/6                                            
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       56.89633            
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      113.79267            
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       85.34450            
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      142.24083            
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       28.44817            
REMARK 290   SMTRY1   7 -0.500000  0.866025  0.000000        0.00000            
REMARK 290   SMTRY2   7  0.866025  0.500000  0.000000        0.00000            
REMARK 290   SMTRY3   7  0.000000  0.000000 -1.000000       56.89633            
REMARK 290   SMTRY1   8  1.000000  0.000000  0.000000        0.00000            
REMARK 290   SMTRY2   8  0.000000 -1.000000  0.000000        0.00000            
REMARK 290   SMTRY3   8  0.000000  0.000000 -1.000000        0.00000            
REMARK 290   SMTRY1   9 -0.500000 -0.866025  0.000000        0.00000            
REMARK 290   SMTRY2   9 -0.866025  0.500000  0.000000        0.00000            
REMARK 290   SMTRY3   9  0.000000  0.000000 -1.000000      113.79267            
REMARK 290   SMTRY1  10  0.500000 -0.866025  0.000000        0.00000            
REMARK 290   SMTRY2  10 -0.866025 -0.500000  0.000000        0.00000            
REMARK 290   SMTRY3  10  0.000000  0.000000 -1.000000      142.24083            
REMARK 290   SMTRY1  11 -1.000000  0.000000  0.000000        0.00000            
REMARK 290   SMTRY2  11  0.000000  1.000000  0.000000        0.00000            
REMARK 290   SMTRY3  11  0.000000  0.000000 -1.000000       85.34450            
REMARK 290   SMTRY1  12  0.500000  0.866025  0.000000        0.00000            
REMARK 290   SMTRY2  12  0.866025 -0.500000  0.000000        0.00000            
REMARK 290   SMTRY3  12  0.000000  0.000000 -1.000000       28.44817            
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 375                                                                      
REMARK 375 SPECIAL POSITION                                                     
REMARK 375 THE FOLLOWING ATOMS ARE FOUND TO BE WITHIN 0.15 ANGSTROMS            
REMARK 375 OF A SYMMETRY RELATED ATOM AND ARE ASSUMED TO BE ON SPECIAL          
REMARK 375 POSITIONS.                                                           
REMARK 375                                                                      
REMARK 375 ATOM RES CSSEQI                                                      
REMARK 375      HOH A 598  LIES ON A SPECIAL POSITION.                          
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     LEU A   -18                                                      
REMARK 465     PRO A   -17                                                      
REMARK 465     ARG A   -16                                                      
REMARK 465     GLU A   -15                                                      
REMARK 465     THR A   -14                                                      
REMARK 465     ASP A   -13                                                      
REMARK 465     GLU A   -12                                                      
REMARK 465     GLU A   -11                                                      
REMARK 465     PRO A   -10                                                      
REMARK 465     GLU A    -9                                                      
REMARK 465     GLU A    -8                                                      
REMARK 465     PRO A    -7                                                      
REMARK 465     GLY A    -6                                                      
REMARK 465     LYS A    -5                                                      
REMARK 465     LYS A    -4                                                      
REMARK 465     GLY A    -3                                                      
REMARK 465     SER A    -2                                                      
REMARK 465     GLY A   158                                                      
REMARK 465     PHE A   159                                                      
REMARK 465     PRO A   160                                                      
REMARK 465     LEU A   161                                                      
REMARK 465     ASN A   162                                                      
REMARK 465     GLN A   163                                                      
REMARK 465     SER A   164                                                      
REMARK 465     GLU A   165                                                      
REMARK 465     VAL A   166                                                      
REMARK 465     LEU A   167                                                      
REMARK 465     VAL A   312                                                      
REMARK 465     ALA A   313                                                      
REMARK 465     THR A   314                                                      
REMARK 465     SER A   315                                                      
REMARK 465     GLN A   316                                                      
REMARK 465     ASP A   317                                                      
REMARK 465     PRO A   387                                                      
REMARK 465     GLN A   388                                                      
REMARK 465     THR A   389                                                      
REMARK 465     ASP A   390                                                      
REMARK 465     GLU A   391                                                      
REMARK 465     SER A   392                                                      
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    HIS A  89       52.90   -104.17                                   
REMARK 500    PHE A 108      -60.76    -99.18                                   
REMARK 500    ALA A 122     -165.63    -78.11                                   
REMARK 500    TRP A 197      -87.76   -139.17                                   
REMARK 500    ASN A 293       12.18     58.65                                   
REMARK 500    ASP A 363     -169.32   -126.66                                   
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 IOD A 401                 
REMARK 800                                                                      
REMARK 800 SITE_IDENTIFIER: AC2                                                 
REMARK 800 EVIDENCE_CODE: SOFTWARE                                              
REMARK 800 SITE_DESCRIPTION: BINDING SITE FOR RESIDUE IOD A 402                 
REMARK 800                                                                      
REMARK 800 SITE_IDENTIFIER: AC3                                                 
REMARK 800 EVIDENCE_CODE: SOFTWARE                                              
REMARK 800 SITE_DESCRIPTION: BINDING SITE FOR RESIDUE IOD A 403                 
REMARK 800                                                                      
REMARK 800 SITE_IDENTIFIER: AC4                                                 
REMARK 800 EVIDENCE_CODE: SOFTWARE                                              
REMARK 800 SITE_DESCRIPTION: BINDING SITE FOR RESIDUE DWA A 404                 
REMARK 800                                                                      
REMARK 800 SITE_IDENTIFIER: AC5                                                 
REMARK 800 EVIDENCE_CODE: SOFTWARE                                              
REMARK 800 SITE_DESCRIPTION: BINDING SITE FOR RESIDUE DMS A 405                 
REMARK 900                                                                      
REMARK 900 RELATED ENTRIES                                                      
REMARK 900 RELATED ID: 4FRJ   RELATED DB: PDB                                   
REMARK 900 RELATED ID: 4FRK   RELATED DB: PDB                                   
DBREF  4FRI A  -18   392  UNP    P56817   BACE1_HUMAN     43    453             
SEQADV 4FRI LYS A   -5  UNP  P56817    ARG    56 ENGINEERED MUTATION            
SEQADV 4FRI LYS A   -4  UNP  P56817    ARG    57 ENGINEERED MUTATION            
SEQRES   1 A  411  LEU PRO ARG GLU THR ASP GLU GLU PRO GLU GLU PRO GLY          
SEQRES   2 A  411  LYS LYS GLY SER PHE VAL GLU MET VAL ASP ASN LEU ARG          
SEQRES   3 A  411  GLY LYS SER GLY GLN GLY TYR TYR VAL GLU MET THR VAL          
SEQRES   4 A  411  GLY SER PRO PRO GLN THR LEU ASN ILE LEU VAL ASP THR          
SEQRES   5 A  411  GLY SER SER ASN PHE ALA VAL GLY ALA ALA PRO HIS PRO          
SEQRES   6 A  411  PHE LEU HIS ARG TYR TYR GLN ARG GLN LEU SER SER THR          
SEQRES   7 A  411  TYR ARG ASP LEU ARG LYS GLY VAL TYR VAL PRO TYR THR          
SEQRES   8 A  411  GLN GLY LYS TRP GLU GLY GLU LEU GLY THR ASP LEU VAL          
SEQRES   9 A  411  SER ILE PRO HIS GLY PRO ASN VAL THR VAL ARG ALA ASN          
SEQRES  10 A  411  ILE ALA ALA ILE THR GLU SER ASP LYS PHE PHE ILE ASN          
SEQRES  11 A  411  GLY SER ASN TRP GLU GLY ILE LEU GLY LEU ALA TYR ALA          
SEQRES  12 A  411  GLU ILE ALA ARG PRO ASP ASP SER LEU GLU PRO PHE PHE          
SEQRES  13 A  411  ASP SER LEU VAL LYS GLN THR HIS VAL PRO ASN LEU PHE          
SEQRES  14 A  411  SER LEU GLN LEU CYS GLY ALA GLY PHE PRO LEU ASN GLN          
SEQRES  15 A  411  SER GLU VAL LEU ALA SER VAL GLY GLY SER MET ILE ILE          
SEQRES  16 A  411  GLY GLY ILE ASP HIS SER LEU TYR THR GLY SER LEU TRP          
SEQRES  17 A  411  TYR THR PRO ILE ARG ARG GLU TRP TYR TYR GLU VAL ILE          
SEQRES  18 A  411  ILE VAL ARG VAL GLU ILE ASN GLY GLN ASP LEU LYS MET          
SEQRES  19 A  411  ASP CYS LYS GLU TYR ASN TYR ASP LYS SER ILE VAL ASP          
SEQRES  20 A  411  SER GLY THR THR ASN LEU ARG LEU PRO LYS LYS VAL PHE          
SEQRES  21 A  411  GLU ALA ALA VAL LYS SER ILE LYS ALA ALA SER SER THR          
SEQRES  22 A  411  GLU LYS PHE PRO ASP GLY PHE TRP LEU GLY GLU GLN LEU          
SEQRES  23 A  411  VAL CYS TRP GLN ALA GLY THR THR PRO TRP ASN ILE PHE          
SEQRES  24 A  411  PRO VAL ILE SER LEU TYR LEU MET GLY GLU VAL THR ASN          
SEQRES  25 A  411  GLN SER PHE ARG ILE THR ILE LEU PRO GLN GLN TYR LEU          
SEQRES  26 A  411  ARG PRO VAL GLU ASP VAL ALA THR SER GLN ASP ASP CYS          
SEQRES  27 A  411  TYR LYS PHE ALA ILE SER GLN SER SER THR GLY THR VAL          
SEQRES  28 A  411  MET GLY ALA VAL ILE MET GLU GLY PHE TYR VAL VAL PHE          
SEQRES  29 A  411  ASP ARG ALA ARG LYS ARG ILE GLY PHE ALA VAL SER ALA          
SEQRES  30 A  411  CYS HIS VAL HIS ASP GLU PHE ARG THR ALA ALA VAL GLU          
SEQRES  31 A  411  GLY PRO PHE VAL THR LEU ASP MET GLU ASP CYS GLY TYR          
SEQRES  32 A  411  ASN ILE PRO GLN THR ASP GLU SER                              
HET    IOD  A 401       1                                                       
HET    IOD  A 402       1                                                       
HET    IOD  A 403       1                                                       
HET    DWA  A 404      27                                                       
HET    DMS  A 405       4                                                       
HETNAM     IOD IODIDE ION                                                       
HETNAM     DWA (4R)-4-[3-(2-FLUOROPYRIDIN-3-YL)PHENYL]-4-(4-                    
HETNAM   2 DWA  METHOXYPHENYL)-4,5-DIHYDRO-1,3-OXAZOL-2-AMINE                   
HETNAM     DMS DIMETHYL SULFOXIDE                                               
FORMUL   2  IOD    3(I 1-)                                                      
FORMUL   5  DWA    C21 H18 F N3 O2                                              
FORMUL   6  DMS    C2 H6 O S                                                    
FORMUL   7  HOH   *213(H2 O)                                                    
HELIX    1   1 GLN A   53  SER A   57  5                                   5    
HELIX    2   2 TYR A  123  ALA A  127  5                                   5    
HELIX    3   3 PRO A  135  THR A  144  1                                  10    
HELIX    4   4 ASP A  180  SER A  182  5                                   3    
HELIX    5   5 ASP A  216  TYR A  222  5                                   7    
HELIX    6   6 LYS A  238  SER A  252  1                                  15    
HELIX    7   7 PRO A  258  LEU A  263  1                                   6    
HELIX    8   8 PRO A  276  PHE A  280  5                                   5    
HELIX    9   9 LEU A  301  TYR A  305  1                                   5    
HELIX   10  10 GLY A  334  GLU A  339  1                                   6    
HELIX   11  11 ARG A  347  ARG A  349  5                                   3    
HELIX   12  12 ASP A  378  GLY A  383  5                                   6    
SHEET    1   A 9 ARG A  61  TYR A  71  0                                        
SHEET    2   A 9 GLY A  74  SER A  86 -1  O  TRP A  76   N  VAL A  69           
SHEET    3   A 9 TYR A  14  VAL A  20 -1  N  THR A  19   O  SER A  86           
SHEET    4   A 9 LEU A   6  LYS A   9 -1  N  ARG A   7   O  TYR A  15           
SHEET    5   A 9 SER A 169  ILE A 176 -1  O  VAL A 170   N  GLY A   8           
SHEET    6   A 9 PHE A 150  LEU A 154 -1  N  GLN A 153   O  SER A 173           
SHEET    7   A 9 PHE A 341  ASP A 346 -1  O  PHE A 345   N  PHE A 150           
SHEET    8   A 9 ARG A 351  SER A 357 -1  O  GLY A 353   N  VAL A 344           
SHEET    9   A 9 TYR A 184  PRO A 192 -1  N  THR A 191   O  ILE A 352           
SHEET    1   B13 ARG A  61  TYR A  71  0                                        
SHEET    2   B13 GLY A  74  SER A  86 -1  O  TRP A  76   N  VAL A  69           
SHEET    3   B13 VAL A  95  ASP A 106 -1  O  VAL A  95   N  VAL A  85           
SHEET    4   B13 PHE A  38  GLY A  41  1  N  VAL A  40   O  ILE A 102           
SHEET    5   B13 GLY A 117  GLY A 120 -1  O  ILE A 118   N  ALA A  39           
SHEET    6   B13 GLN A  25  ASP A  32  1  N  LEU A  30   O  LEU A 119           
SHEET    7   B13 TYR A  14  VAL A  20 -1  N  TYR A  14   O  VAL A  31           
SHEET    8   B13 LEU A   6  LYS A   9 -1  N  ARG A   7   O  TYR A  15           
SHEET    9   B13 SER A 169  ILE A 176 -1  O  VAL A 170   N  GLY A   8           
SHEET   10   B13 PHE A 150  LEU A 154 -1  N  GLN A 153   O  SER A 173           
SHEET   11   B13 PHE A 341  ASP A 346 -1  O  PHE A 345   N  PHE A 150           
SHEET   12   B13 ARG A 351  SER A 357 -1  O  GLY A 353   N  VAL A 344           
SHEET   13   B13 TYR A 184  PRO A 192 -1  N  THR A 191   O  ILE A 352           
SHEET    1   C 5 GLN A 211  ASP A 212  0                                        
SHEET    2   C 5 ILE A 203  ILE A 208 -1  N  ILE A 208   O  GLN A 211           
SHEET    3   C 5 ILE A 283  MET A 288 -1  O  SER A 284   N  GLU A 207           
SHEET    4   C 5 GLN A 294  ILE A 300 -1  O  ILE A 298   N  LEU A 285           
SHEET    5   C 5 ALA A 369  VAL A 375 -1  O  GLU A 371   N  ARG A 297           
SHEET    1   D 4 SER A 225  VAL A 227  0                                        
SHEET    2   D 4 THR A 331  MET A 333  1  O  MET A 333   N  ILE A 226           
SHEET    3   D 4 LEU A 234  PRO A 237 -1  N  ARG A 235   O  VAL A 332           
SHEET    4   D 4 ILE A 324  SER A 327  1  O  SER A 325   N  LEU A 236           
SHEET    1   E 3 VAL A 268  CYS A 269  0                                        
SHEET    2   E 3 CYS A 319  PHE A 322 -1  O  TYR A 320   N  VAL A 268           
SHEET    3   E 3 LEU A 306  PRO A 308 -1  N  ARG A 307   O  LYS A 321           
SSBOND   1 CYS A  155    CYS A  359                          1555   1555  2.07  
SSBOND   2 CYS A  217    CYS A  382                          1555   1555  2.03  
SSBOND   3 CYS A  269    CYS A  319                          1555   1555  2.04  
CISPEP   1 SER A   22    PRO A   23          0        -2.31                     
CISPEP   2 ARG A  128    PRO A  129          0         2.42                     
CISPEP   3 TYR A  222    ASP A  223          0         1.38                     
CISPEP   4 GLY A  372    PRO A  373          0         0.84                     
SITE     1 AC1  2 GLU A 104  SER A 105                                          
SITE     1 AC2  1 LYS A 107                                                     
SITE     1 AC3  3 TYR A 222  LYS A 239  HOH A 636                               
SITE     1 AC4 13 GLY A  11  GLN A  12  GLY A  13  LEU A  30                    
SITE     2 AC4 13 ASP A  32  SER A  35  VAL A  69  TRP A  76                    
SITE     3 AC4 13 PHE A 108  ILE A 118  ASP A 228  GLY A 230                    
SITE     4 AC4 13 HOH A 637                                                     
SITE     1 AC5  1 ARG A  96                                                     
CRYST1  101.461  101.461  170.689  90.00  90.00 120.00 P 61 2 2     12          
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      0.009856  0.005690  0.000000        0.00000                         
SCALE2      0.000000  0.011381  0.000000        0.00000                         
SCALE3      0.000000  0.000000  0.005859        0.00000                         
(ATOM LINES ARE NOT SHOWN.)
END                                                                             
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