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Database: PDB
Entry: 4J1H
LinkDB: 4J1H
Original site: 4J1H 
HEADER    HYDROLASE/HYDROLASE INHIBITOR           01-FEB-13   4J1H              
TITLE     CRYSTAL STRUCTURE OF BACE-1 IN COMPLEX WITH 5-CYANO-PYRIDINE-2-       
TITLE    2 CARBOXYLIC ACID [3-((4S,6R)-2-AMINO-4-METHYL-6-TRIFLUOROMETHYL-5,6-  
TITLE    3 DIHYDRO-4H-[1,3]OXAZIN-4-YL)-4-FLUORO-PHENYL]-AMIDE                  
COMPND    MOL_ID: 1;                                                            
COMPND   2 MOLECULE: BETA-SECRETASE 1;                                          
COMPND   3 CHAIN: A;                                                            
COMPND   4 SYNONYM: ASPARTYL PROTEASE 2, ASP2, ASP 2, BETA-SITE AMYLOID         
COMPND   5 PRECURSOR PROTEIN CLEAVING ENZYME 1, BETA-SITE APP CLEAVING ENZYME 1,
COMPND   6 MEMAPSIN-2, MEMBRANE-ASSOCIATED ASPARTIC PROTEASE 2;                 
COMPND   7 EC: 3.4.23.46;                                                       
COMPND   8 ENGINEERED: YES;                                                     
COMPND   9 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: BACE1, BACE, KIAA1149;                                         
SOURCE   6 EXPRESSION_SYSTEM: ESCHERICHIA COLI;                                 
SOURCE   7 EXPRESSION_SYSTEM_TAXID: 562                                         
KEYWDS    PROTEASE INHIBITOR, HYDROLASE-HYDROLASE INHIBITOR COMPLEX             
EXPDTA    X-RAY DIFFRACTION                                                     
AUTHOR    A.KUGLSTATTER,M.STIHLE                                                
REVDAT   3   15-NOV-17 4J1H    1       REMARK                                   
REVDAT   2   19-JUN-13 4J1H    1       JRNL                                     
REVDAT   1   01-MAY-13 4J1H    0                                                
JRNL        AUTH   H.HILPERT,W.GUBA,T.J.WOLTERING,W.WOSTL,E.PINARD,H.MAUSER,    
JRNL        AUTH 2 A.V.MAYWEG,M.ROGERS-EVANS,R.HUMM,D.KRUMMENACHER,T.MUSER,     
JRNL        AUTH 3 C.SCHNIDER,H.JACOBSEN,L.OZMEN,A.BERGADANO,D.W.BANNER,        
JRNL        AUTH 4 R.HOCHSTRASSER,A.KUGLSTATTER,P.DAVID-PIERSON,H.FISCHER,      
JRNL        AUTH 5 A.POLARA,R.NARQUIZIAN                                        
JRNL        TITL   BETA-SECRETASE (BACE1) INHIBITORS WITH HIGH IN VIVO EFFICACY 
JRNL        TITL 2 SUITABLE FOR CLINICAL EVALUATION IN ALZHEIMER S DISEASE      
JRNL        REF    J.MED.CHEM.                   V.  56  3980 2013              
JRNL        REFN                   ISSN 0022-2623                               
JRNL        PMID   23590342                                                     
JRNL        DOI    10.1021/JM400225M                                            
REMARK   2                                                                      
REMARK   2 RESOLUTION.    2.20 ANGSTROMS.                                       
REMARK   3                                                                      
REMARK   3 REFINEMENT.                                                          
REMARK   3   PROGRAM     : REFMAC                                               
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) : 2.20                           
REMARK   3   RESOLUTION RANGE LOW  (ANGSTROMS) : 47.56                          
REMARK   3   DATA CUTOFF            (SIGMA(F)) : NULL                           
REMARK   3   COMPLETENESS FOR RANGE        (%) : 100.0                          
REMARK   3   NUMBER OF REFLECTIONS             : 26048                          
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) : 0.188                           
REMARK   3   R VALUE            (WORKING SET) : 0.186                           
REMARK   3   FREE R VALUE                     : 0.236                           
REMARK   3   FREE R VALUE TEST SET SIZE   (%) : 5.000                           
REMARK   3   FREE R VALUE TEST SET COUNT      : 1375                            
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) : 2.20                         
REMARK   3   BIN RESOLUTION RANGE LOW        (A) : 2.26                         
REMARK   3   REFLECTION IN BIN     (WORKING SET) : 1890                         
REMARK   3   BIN COMPLETENESS (WORKING+TEST) (%) : 100.0                        
REMARK   3   BIN R VALUE           (WORKING SET) : 0.3260                       
REMARK   3   BIN FREE R VALUE SET COUNT          : 84                           
REMARK   3   BIN FREE R VALUE                    : 0.3220                       
REMARK   3                                                                      
REMARK   3  NUMBER OF NON-HYDROGEN ATOMS USED IN REFINEMENT.                    
REMARK   3   PROTEIN ATOMS            : 2916                                    
REMARK   3   NUCLEIC ACID ATOMS       : 0                                       
REMARK   3   HETEROGEN ATOMS          : 36                                      
REMARK   3   SOLVENT ATOMS            : 128                                     
REMARK   3                                                                      
REMARK   3  B VALUES.                                                           
REMARK   3   FROM WILSON PLOT           (A**2) : 45.30                          
REMARK   3   MEAN B VALUE      (OVERALL, A**2) : 48.51                          
REMARK   3   OVERALL ANISOTROPIC B VALUE.                                       
REMARK   3    B11 (A**2) : -0.71000                                             
REMARK   3    B22 (A**2) : -0.71000                                             
REMARK   3    B33 (A**2) : 1.07000                                              
REMARK   3    B12 (A**2) : -0.36000                                             
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): 0.197         
REMARK   3   ESU BASED ON FREE R VALUE                       (A): 0.182         
REMARK   3   ESU BASED ON MAXIMUM LIKELIHOOD                 (A): 0.122         
REMARK   3   ESU FOR B VALUES BASED ON MAXIMUM LIKELIHOOD (A**2): 11.184        
REMARK   3                                                                      
REMARK   3 CORRELATION COEFFICIENTS.                                            
REMARK   3   CORRELATION COEFFICIENT FO-FC      : 0.959                         
REMARK   3   CORRELATION COEFFICIENT FO-FC FREE : 0.937                         
REMARK   3                                                                      
REMARK   3  RMS DEVIATIONS FROM IDEAL VALUES        COUNT    RMS    WEIGHT      
REMARK   3   BOND LENGTHS REFINED ATOMS        (A):  3027 ; 0.018 ; 0.019       
REMARK   3   BOND LENGTHS OTHERS               (A):  NULL ;  NULL ;  NULL       
REMARK   3   BOND ANGLES REFINED ATOMS   (DEGREES):  4114 ; 1.984 ; 1.957       
REMARK   3   BOND ANGLES OTHERS          (DEGREES):  NULL ;  NULL ;  NULL       
REMARK   3   TORSION ANGLES, PERIOD 1    (DEGREES):   366 ; 7.411 ; 5.000       
REMARK   3   TORSION ANGLES, PERIOD 2    (DEGREES):   138 ;31.400 ;23.623       
REMARK   3   TORSION ANGLES, PERIOD 3    (DEGREES):   476 ;16.704 ;15.000       
REMARK   3   TORSION ANGLES, PERIOD 4    (DEGREES):    18 ;20.424 ;15.000       
REMARK   3   CHIRAL-CENTER RESTRAINTS       (A**3):   444 ; 0.132 ; 0.200       
REMARK   3   GENERAL PLANES REFINED ATOMS      (A):  2319 ; 0.010 ; 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):  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  : 1                                          
REMARK   3                                                                      
REMARK   3   TLS GROUP : 1                                                      
REMARK   3    NUMBER OF COMPONENTS GROUP : 3                                    
REMARK   3    COMPONENTS        C SSSEQI   TO  C SSSEQI                         
REMARK   3    RESIDUE RANGE :   A  1001        A  1128                          
REMARK   3    RESIDUE RANGE :   A   501        A   504                          
REMARK   3    RESIDUE RANGE :   A    57        A   446                          
REMARK   3    ORIGIN FOR THE GROUP (A):  12.9919  41.2625  -0.0161              
REMARK   3    T TENSOR                                                          
REMARK   3      T11:   0.0395 T22:   0.0285                                     
REMARK   3      T33:   0.0410 T12:  -0.0213                                     
REMARK   3      T13:   0.0131 T23:  -0.0052                                     
REMARK   3    L TENSOR                                                          
REMARK   3      L11:   3.2084 L22:   0.9589                                     
REMARK   3      L33:   1.3650 L12:  -1.4045                                     
REMARK   3      L13:  -1.1282 L23:   0.3726                                     
REMARK   3    S TENSOR                                                          
REMARK   3      S11:   0.0130 S12:  -0.0125 S13:   0.2659                       
REMARK   3      S21:   0.0128 S22:   0.0223 S23:  -0.1690                       
REMARK   3      S31:  -0.0333 S32:   0.0254 S33:  -0.0353                       
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 4J1H COMPLIES WITH FORMAT V. 3.30, 13-JUL-11                         
REMARK 100                                                                      
REMARK 100 THIS ENTRY HAS BEEN PROCESSED BY RCSB ON 07-FEB-13.                  
REMARK 100 THE DEPOSITION ID IS D_1000077476.                                   
REMARK 200                                                                      
REMARK 200 EXPERIMENTAL DETAILS                                                 
REMARK 200  EXPERIMENT TYPE                : X-RAY DIFFRACTION                  
REMARK 200  DATE OF DATA COLLECTION        : 30-APR-12                          
REMARK 200  TEMPERATURE           (KELVIN) : 100                                
REMARK 200  PH                             : 7.0                                
REMARK 200  NUMBER OF CRYSTALS USED        : 1                                  
REMARK 200                                                                      
REMARK 200  SYNCHROTRON              (Y/N) : Y                                  
REMARK 200  RADIATION SOURCE               : SLS                                
REMARK 200  BEAMLINE                       : X10SA                              
REMARK 200  X-RAY GENERATOR MODEL          : NULL                               
REMARK 200  MONOCHROMATIC OR LAUE    (M/L) : M                                  
REMARK 200  WAVELENGTH OR RANGE        (A) : 1.0000                             
REMARK 200  MONOCHROMATOR                  : NULL                               
REMARK 200  OPTICS                         : NULL                               
REMARK 200                                                                      
REMARK 200  DETECTOR TYPE                  : PIXEL                              
REMARK 200  DETECTOR MANUFACTURER          : DECTRIS PILATUS 6M                 
REMARK 200  INTENSITY-INTEGRATION SOFTWARE : XDS                                
REMARK 200  DATA SCALING SOFTWARE          : SCALA                              
REMARK 200                                                                      
REMARK 200  NUMBER OF UNIQUE REFLECTIONS   : 30618                              
REMARK 200  RESOLUTION RANGE HIGH      (A) : 2.120                              
REMARK 200  RESOLUTION RANGE LOW       (A) : 49.120                             
REMARK 200  REJECTION CRITERIA  (SIGMA(I)) : NULL                               
REMARK 200                                                                      
REMARK 200 OVERALL.                                                             
REMARK 200  COMPLETENESS FOR RANGE     (%) : 100.0                              
REMARK 200  DATA REDUNDANCY                : 19.30                              
REMARK 200  R MERGE                    (I) : NULL                               
REMARK 200  R SYM                      (I) : 0.15200                            
REMARK 200  <I/SIGMA(I)> FOR THE DATA SET  : 15.6000                            
REMARK 200                                                                      
REMARK 200 IN THE HIGHEST RESOLUTION SHELL.                                     
REMARK 200  HIGHEST RESOLUTION SHELL, RANGE HIGH (A) : 2.12                     
REMARK 200  HIGHEST RESOLUTION SHELL, RANGE LOW  (A) : 2.23                     
REMARK 200  COMPLETENESS FOR SHELL     (%) : 100.0                              
REMARK 200  DATA REDUNDANCY IN SHELL       : 19.20                              
REMARK 200  R MERGE FOR SHELL          (I) : NULL                               
REMARK 200  R SYM FOR SHELL            (I) : NULL                               
REMARK 200  <I/SIGMA(I)> FOR SHELL         : 1.400                              
REMARK 200                                                                      
REMARK 200 DIFFRACTION PROTOCOL: SINGLE WAVELENGTH                              
REMARK 200 METHOD USED TO DETERMINE THE STRUCTURE: FOURIER SYNTHESIS            
REMARK 200 SOFTWARE USED: REFMAC                                                
REMARK 200 STARTING MODEL: NULL                                                 
REMARK 200                                                                      
REMARK 200 REMARK: NULL                                                         
REMARK 280                                                                      
REMARK 280 CRYSTAL                                                              
REMARK 280 SOLVENT CONTENT, VS   (%): 56.40                                     
REMARK 280 MATTHEWS COEFFICIENT, VM (ANGSTROMS**3/DA): 2.82                     
REMARK 280                                                                      
REMARK 280 CRYSTALLIZATION CONDITIONS: 2.5M SODIUM FORMATE, 100MM HEPES, PH     
REMARK 280  7.0, VAPOR DIFFUSION, SITTING DROP, TEMPERATURE 298K                
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       56.29100            
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      112.58200            
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       84.43650            
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      140.72750            
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       28.14550            
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       56.29100            
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      112.58200            
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      140.72750            
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       84.43650            
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       28.14550            
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     GLU A    46                                                      
REMARK 465     THR A    47                                                      
REMARK 465     ASP A    48                                                      
REMARK 465     GLU A    49                                                      
REMARK 465     GLU A    50                                                      
REMARK 465     PRO A    51                                                      
REMARK 465     GLU A    52                                                      
REMARK 465     GLU A    53                                                      
REMARK 465     PRO A    54                                                      
REMARK 465     GLY A    55                                                      
REMARK 465     ARG A    56                                                      
REMARK 465     ALA A   218                                                      
REMARK 465     GLY A   219                                                      
REMARK 465     PHE A   220                                                      
REMARK 465     PRO A   221                                                      
REMARK 465     LEU A   222                                                      
REMARK 465     ASN A   223                                                      
REMARK 465     GLN A   224                                                      
REMARK 465     SER A   225                                                      
REMARK 465     GLU A   226                                                      
REMARK 465     VAL A   227                                                      
REMARK 465     LEU A   228                                                      
REMARK 465     ALA A   229                                                      
REMARK 465     GLY A   334                                                      
REMARK 465     THR A   335                                                      
REMARK 465     THR A   336                                                      
REMARK 465     ALA A   374                                                      
REMARK 465     THR A   375                                                      
REMARK 465     SER A   376                                                      
REMARK 465     GLN A   377                                                      
REMARK 465     ASP A   378                                                      
REMARK 465     ILE A   447                                                      
REMARK 465     PRO A   448                                                      
REMARK 465     GLN A   449                                                      
REMARK 465     THR A   450                                                      
REMARK 465     ASP A   451                                                      
REMARK 465     GLU A   452                                                      
REMARK 465     SER A   453                                                      
REMARK 465     THR A   454                                                      
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     ASP A 372    CG   OD1  OD2                                       
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 115   NE  -  CZ  -  NH1 ANGL. DEV. =  -3.4 DEGREES          
REMARK 500    ASP A 199   CB  -  CG  -  OD2 ANGL. DEV. =   5.8 DEGREES          
REMARK 500    ARG A 410   NE  -  CZ  -  NH2 ANGL. DEV. =  -3.6 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    HIS A 150       46.61   -102.54                                   
REMARK 500    TRP A 258      -89.15   -135.81                                   
REMARK 500    SER A 314       21.11    -65.45                                   
REMARK 500    ALA A 429      150.33    -46.99                                   
REMARK 500                                                                      
REMARK 500 REMARK: NULL                                                         
REMARK 620                                                                      
REMARK 620 METAL COORDINATION                                                   
REMARK 620 (M=MODEL NUMBER; RES=RESIDUE NAME; C=CHAIN IDENTIFIER;               
REMARK 620 SSEQ=SEQUENCE NUMBER; I=INSERTION CODE):                             
REMARK 620                                                                      
REMARK 620 COORDINATION ANGLES FOR:  M RES CSSEQI METAL                         
REMARK 620                              NA A 502  NA                            
REMARK 620 N RES CSSEQI ATOM                                                    
REMARK 620 1 VAL A 202   O                                                      
REMARK 620 2 HOH A1104   O    92.1                                              
REMARK 620 3 THR A 205   O    89.2 163.9                                        
REMARK 620 N                    1     2                                         
REMARK 620                                                                      
REMARK 620 COORDINATION ANGLES FOR:  M RES CSSEQI METAL                         
REMARK 620                              NA A 501  NA                            
REMARK 620 N RES CSSEQI ATOM                                                    
REMARK 620 1 HIS A 242   O                                                      
REMARK 620 2 TYR A 245   O    75.8                                              
REMARK 620 3 HOH A1064   O    78.7  70.4                                        
REMARK 620 N                    1     2                                         
REMARK 800                                                                      
REMARK 800 SITE                                                                 
REMARK 800 SITE_IDENTIFIER: AC1                                                 
REMARK 800 EVIDENCE_CODE: SOFTWARE                                              
REMARK 800 SITE_DESCRIPTION: BINDING SITE FOR RESIDUE NA A 501                  
REMARK 800                                                                      
REMARK 800 SITE_IDENTIFIER: AC2                                                 
REMARK 800 EVIDENCE_CODE: SOFTWARE                                              
REMARK 800 SITE_DESCRIPTION: BINDING SITE FOR RESIDUE NA A 502                  
REMARK 800                                                                      
REMARK 800 SITE_IDENTIFIER: AC3                                                 
REMARK 800 EVIDENCE_CODE: SOFTWARE                                              
REMARK 800 SITE_DESCRIPTION: BINDING SITE FOR RESIDUE DMS A 503                 
REMARK 800                                                                      
REMARK 800 SITE_IDENTIFIER: AC4                                                 
REMARK 800 EVIDENCE_CODE: SOFTWARE                                              
REMARK 800 SITE_DESCRIPTION: BINDING SITE FOR RESIDUE 1HJ A 504                 
REMARK 900                                                                      
REMARK 900 RELATED ENTRIES                                                      
REMARK 900 RELATED ID: 4J0P   RELATED DB: PDB                                   
REMARK 900 RELATED ID: 4J0T   RELATED DB: PDB                                   
REMARK 900 RELATED ID: 4J0V   RELATED DB: PDB                                   
REMARK 900 RELATED ID: 4J0Y   RELATED DB: PDB                                   
REMARK 900 RELATED ID: 4J0Z   RELATED DB: PDB                                   
REMARK 900 RELATED ID: 4J17   RELATED DB: PDB                                   
REMARK 900 RELATED ID: 4J1C   RELATED DB: PDB                                   
REMARK 900 RELATED ID: 4J1E   RELATED DB: PDB                                   
REMARK 900 RELATED ID: 4J1F   RELATED DB: PDB                                   
REMARK 900 RELATED ID: 4J1I   RELATED DB: PDB                                   
REMARK 900 RELATED ID: 4J1K   RELATED DB: PDB                                   
DBREF  4J1H A   46   454  UNP    P56817   BACE1_HUMAN     46    454             
SEQADV 4J1H ALA A  307  UNP  P56817    LYS   307 ENGINEERED MUTATION            
SEQRES   1 A  409  GLU THR ASP GLU GLU PRO GLU GLU PRO GLY ARG ARG GLY          
SEQRES   2 A  409  SER PHE VAL GLU MET VAL ASP ASN LEU ARG GLY LYS SER          
SEQRES   3 A  409  GLY GLN GLY TYR TYR VAL GLU MET THR VAL GLY SER PRO          
SEQRES   4 A  409  PRO GLN THR LEU ASN ILE LEU VAL ASP THR GLY SER SER          
SEQRES   5 A  409  ASN PHE ALA VAL GLY ALA ALA PRO HIS PRO PHE LEU HIS          
SEQRES   6 A  409  ARG TYR TYR GLN ARG GLN LEU SER SER THR TYR ARG ASP          
SEQRES   7 A  409  LEU ARG LYS GLY VAL TYR VAL PRO TYR THR GLN GLY LYS          
SEQRES   8 A  409  TRP GLU GLY GLU LEU GLY THR ASP LEU VAL SER ILE PRO          
SEQRES   9 A  409  HIS GLY PRO ASN VAL THR VAL ARG ALA ASN ILE ALA ALA          
SEQRES  10 A  409  ILE THR GLU SER ASP LYS PHE PHE ILE ASN GLY SER ASN          
SEQRES  11 A  409  TRP GLU GLY ILE LEU GLY LEU ALA TYR ALA GLU ILE ALA          
SEQRES  12 A  409  ARG PRO ASP ASP SER LEU GLU PRO PHE PHE ASP SER LEU          
SEQRES  13 A  409  VAL LYS GLN THR HIS VAL PRO ASN LEU PHE SER LEU GLN          
SEQRES  14 A  409  LEU CYS GLY ALA GLY PHE PRO LEU ASN GLN SER GLU VAL          
SEQRES  15 A  409  LEU ALA SER VAL GLY GLY SER MET ILE ILE GLY GLY ILE          
SEQRES  16 A  409  ASP HIS SER LEU TYR THR GLY SER LEU TRP TYR THR PRO          
SEQRES  17 A  409  ILE ARG ARG GLU TRP TYR TYR GLU VAL ILE ILE VAL ARG          
SEQRES  18 A  409  VAL GLU ILE ASN GLY GLN ASP LEU LYS MET ASP CYS LYS          
SEQRES  19 A  409  GLU TYR ASN TYR ASP LYS SER ILE VAL ASP SER GLY THR          
SEQRES  20 A  409  THR ASN LEU ARG LEU PRO LYS LYS VAL PHE GLU ALA ALA          
SEQRES  21 A  409  VAL ALA SER ILE LYS ALA ALA SER SER THR GLU LYS PHE          
SEQRES  22 A  409  PRO ASP GLY PHE TRP LEU GLY GLU GLN LEU VAL CYS TRP          
SEQRES  23 A  409  GLN ALA GLY THR THR PRO TRP ASN ILE PHE PRO VAL ILE          
SEQRES  24 A  409  SER LEU TYR LEU MET GLY GLU VAL THR ASN GLN SER PHE          
SEQRES  25 A  409  ARG ILE THR ILE LEU PRO GLN GLN TYR LEU ARG PRO VAL          
SEQRES  26 A  409  GLU ASP VAL ALA THR SER GLN ASP ASP CYS TYR LYS PHE          
SEQRES  27 A  409  ALA ILE SER GLN SER SER THR GLY THR VAL MET GLY ALA          
SEQRES  28 A  409  VAL ILE MET GLU GLY PHE TYR VAL VAL PHE ASP ARG ALA          
SEQRES  29 A  409  ARG LYS ARG ILE GLY PHE ALA VAL SER ALA CYS HIS VAL          
SEQRES  30 A  409  HIS ASP GLU PHE ARG THR ALA ALA VAL GLU GLY PRO PHE          
SEQRES  31 A  409  VAL THR LEU ASP MET GLU ASP CYS GLY TYR ASN ILE PRO          
SEQRES  32 A  409  GLN THR ASP GLU SER THR                                      
HET     NA  A 501       1                                                       
HET     NA  A 502       1                                                       
HET    DMS  A 503       4                                                       
HET    1HJ  A 504      30                                                       
HETNAM      NA SODIUM ION                                                       
HETNAM     DMS DIMETHYL SULFOXIDE                                               
HETNAM     1HJ N-{3-[(4S,6R)-2-AMINO-4-METHYL-6-(TRIFLUOROMETHYL)-5,6-          
HETNAM   2 1HJ  DIHYDRO-4H-1,3-OXAZIN-4-YL]-4-FLUOROPHENYL}-5-                  
HETNAM   3 1HJ  CYANOPYRIDINE-2-CARBOXAMIDE                                     
FORMUL   2   NA    2(NA 1+)                                                     
FORMUL   4  DMS    C2 H6 O S                                                    
FORMUL   5  1HJ    C19 H15 F4 N5 O2                                             
FORMUL   6  HOH   *128(H2 O)                                                    
HELIX    1   1 GLN A  114  SER A  118  5                                   5    
HELIX    2   2 TYR A  184  ALA A  188  5                                   5    
HELIX    3   3 PRO A  196  THR A  205  1                                  10    
HELIX    4   4 ASP A  241  SER A  243  5                                   3    
HELIX    5   5 ASP A  277  TYR A  283  5                                   7    
HELIX    6   6 LYS A  299  SER A  314  1                                  16    
HELIX    7   7 PRO A  319  LEU A  324  1                                   6    
HELIX    8   8 LEU A  362  TYR A  366  1                                   5    
HELIX    9   9 GLY A  395  GLU A  400  1                                   6    
HELIX   10  10 ARG A  408  ARG A  410  5                                   3    
HELIX   11  11 ASP A  439  GLY A  444  5                                   6    
SHEET    1   A 9 ARG A 122  PRO A 131  0                                        
SHEET    2   A 9 LYS A 136  SER A 147 -1  O  TRP A 137   N  VAL A 130           
SHEET    3   A 9 TYR A  76  VAL A  81 -1  N  THR A  80   O  SER A 147           
SHEET    4   A 9 LEU A  67  GLY A  69 -1  N  ARG A  68   O  TYR A  76           
SHEET    5   A 9 VAL A 231  ILE A 237 -1  O  VAL A 231   N  GLY A  69           
SHEET    6   A 9 PHE A 211  CYS A 216 -1  N  GLN A 214   O  SER A 234           
SHEET    7   A 9 PHE A 402  ASP A 407 -1  O  VAL A 404   N  LEU A 213           
SHEET    8   A 9 ARG A 412  SER A 418 -1  O  GLY A 414   N  VAL A 405           
SHEET    9   A 9 TYR A 245  PRO A 253 -1  N  THR A 252   O  ILE A 413           
SHEET    1   B13 ARG A 122  PRO A 131  0                                        
SHEET    2   B13 LYS A 136  SER A 147 -1  O  TRP A 137   N  VAL A 130           
SHEET    3   B13 THR A 155  ASP A 167 -1  O  ALA A 162   N  GLU A 140           
SHEET    4   B13 PHE A  99  GLY A 102  1  N  VAL A 101   O  ILE A 163           
SHEET    5   B13 GLY A 178  GLY A 181 -1  O  ILE A 179   N  ALA A 100           
SHEET    6   B13 GLN A  86  ASP A  93  1  N  LEU A  91   O  LEU A 180           
SHEET    7   B13 TYR A  76  VAL A  81 -1  N  MET A  79   O  LEU A  88           
SHEET    8   B13 LEU A  67  GLY A  69 -1  N  ARG A  68   O  TYR A  76           
SHEET    9   B13 VAL A 231  ILE A 237 -1  O  VAL A 231   N  GLY A  69           
SHEET   10   B13 PHE A 211  CYS A 216 -1  N  GLN A 214   O  SER A 234           
SHEET   11   B13 PHE A 402  ASP A 407 -1  O  VAL A 404   N  LEU A 213           
SHEET   12   B13 ARG A 412  SER A 418 -1  O  GLY A 414   N  VAL A 405           
SHEET   13   B13 TYR A 245  PRO A 253 -1  N  THR A 252   O  ILE A 413           
SHEET    1   C 5 GLU A 261  VAL A 262  0                                        
SHEET    2   C 5 SER A 286  VAL A 288 -1  O  SER A 286   N  VAL A 262           
SHEET    3   C 5 THR A 392  MET A 394  1  O  MET A 394   N  ILE A 287           
SHEET    4   C 5 LEU A 295  PRO A 298 -1  N  ARG A 296   O  VAL A 393           
SHEET    5   C 5 ILE A 385  SER A 388  1  O  SER A 386   N  LEU A 297           
SHEET    1   D 5 GLN A 272  ASP A 273  0                                        
SHEET    2   D 5 ILE A 264  ILE A 269 -1  N  ILE A 269   O  GLN A 272           
SHEET    3   D 5 ILE A 344  MET A 349 -1  O  TYR A 347   N  ARG A 266           
SHEET    4   D 5 GLN A 355  ILE A 361 -1  O  ILE A 359   N  LEU A 346           
SHEET    5   D 5 ALA A 430  VAL A 436 -1  O  GLU A 432   N  ARG A 358           
SHEET    1   E 3 VAL A 329  CYS A 330  0                                        
SHEET    2   E 3 CYS A 380  PHE A 383 -1  O  TYR A 381   N  VAL A 329           
SHEET    3   E 3 LEU A 367  PRO A 369 -1  N  ARG A 368   O  LYS A 382           
SSBOND   1 CYS A  216    CYS A  420                          1555   1555  2.11  
SSBOND   2 CYS A  278    CYS A  443                          1555   1555  2.10  
SSBOND   3 CYS A  330    CYS A  380                          1555   1555  2.07  
LINK         O   VAL A 202                NA    NA A 502     1555   1555  2.24  
LINK        NA    NA A 502                 O   HOH A1104     1555   1555  2.40  
LINK         O   THR A 205                NA    NA A 502     1555   1555  2.41  
LINK         O   HIS A 242                NA    NA A 501     1555   1555  2.45  
LINK         O   TYR A 245                NA    NA A 501     1555   1555  2.56  
LINK        NA    NA A 501                 O   HOH A1064     1555   1555  2.67  
CISPEP   1 SER A   83    PRO A   84          0        -7.74                     
CISPEP   2 ARG A  189    PRO A  190          0         3.35                     
CISPEP   3 TYR A  283    ASP A  284          0        -0.72                     
CISPEP   4 GLY A  433    PRO A  434          0        -1.35                     
SITE     1 AC1  3 HIS A 242  TYR A 245  HOH A1064                               
SITE     1 AC2  3 VAL A 202  THR A 205  HOH A1104                               
SITE     1 AC3  2 ARG A 157  GLU A 195                                          
SITE     1 AC4 14 GLY A  72  GLN A  73  GLY A  74  LEU A  91                    
SITE     2 AC4 14 ASP A  93  TYR A 132  PHE A 169  TRP A 176                    
SITE     3 AC4 14 ILE A 179  ASP A 289  SER A 290  GLY A 291                    
SITE     4 AC4 14 THR A 293  ALA A 396                                          
CRYST1  102.685  102.685  168.873  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      0.009739  0.005623  0.000000        0.00000                         
SCALE2      0.000000  0.011245  0.000000        0.00000                         
SCALE3      0.000000  0.000000  0.005922        0.00000                         
(ATOM LINES ARE NOT SHOWN.)
END                                                                             
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