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Database: PDB
Entry: 2WF0
LinkDB: 2WF0
Original site: 2WF0 
HEADER    HYDROLASE                               02-APR-09   2WF0              
TITLE     HUMAN BACE-1 IN COMPLEX WITH 4-ETHYL-N-((1S,2R)-2-HYDROXY-1-          
TITLE    2 (PHENYLMETHYL)-3-(((3-(TRIFLUOROMETHYL)PHENYL)METHYL)AMINO)PROPYL)-8-
TITLE    3 (2-OXO-1-PYRROLIDINYL)-6-QUINOLINECARBOXAMIDE                        
COMPND    MOL_ID: 1;                                                            
COMPND   2 MOLECULE: BETA-SECRETASE 1;                                          
COMPND   3 CHAIN: A;                                                            
COMPND   4 FRAGMENT: RESIDUES 61-452;                                           
COMPND   5 SYNONYM: BETA-SITE AMYLOID PRECURSOR PROTEIN CLEAVING ENZYME 1,      
COMPND   6 MEMBRANE-ASSOCIATED ASPARTIC PROTEASE 2, MEMAPSIN-2, ASPARTYL        
COMPND   7 PROTEASE 2, BETA-SITE APP CLEAVING ENZYME 1, ASP 2, ASP2, BACE-1;    
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 EXPRESSION_SYSTEM: CRICETULUS GRISEUS;                               
SOURCE   6 EXPRESSION_SYSTEM_COMMON: CHINESE HAMSTER;                           
SOURCE   7 EXPRESSION_SYSTEM_TAXID: 10029;                                      
SOURCE   8 EXPRESSION_SYSTEM_CELL: OVARY                                        
KEYWDS    HYDROLASE, MEMAPSIN-2, POLYMORPHISM, GLYCOPROTEIN, ASP-2, BACE-1,     
KEYWDS   2 ZYMOGEN, PROTEASE, MEMBRANE, TRANSMEMBRANE, BETA-SECRETASE,          
KEYWDS   3 DISULFIDE BOND, ASPARTYL PROTEASE, ALTERNATIVE SPLICING, BETA-SITE   
KEYWDS   4 APP CLEAVING ENZYME                                                  
EXPDTA    X-RAY DIFFRACTION                                                     
AUTHOR    N.CHARRIER,B.CLARKE,L.CUTLER,E.DEMONT,C.DINGWALL,R.DUNSDON,J.HAWKINS, 
AUTHOR   2 C.HOWES,J.HUBBARD,I.HUSSAIN,G.MAILE,R.MATICO,J.MOSLEY,A.NAYLOR,      
AUTHOR   3 A.O'BRIEN,S.REDSHAW,P.ROWLAND,V.SOLEIL,K.J.SMITH,S.SWEITZER,         
AUTHOR   4 P.THEOBALD,D.VESEY,D.S.WALTER,G.WAYNE                                
REVDAT   5   15-MAY-19 2WF0    1       REMARK                                   
REVDAT   4   06-MAR-19 2WF0    1       REMARK                                   
REVDAT   3   14-JUL-09 2WF0    1       HETNAM FORMUL                            
REVDAT   2   23-JUN-09 2WF0    1       JRNL                                     
REVDAT   1   19-MAY-09 2WF0    0                                                
JRNL        AUTH   N.CHARRIER,B.CLARKE,L.CUTLER,E.DEMONT,C.DINGWALL,R.DUNSDON,  
JRNL        AUTH 2 J.HAWKINS,C.HOWES,J.HUBBARD,I.HUSSAIN,G.MAILE,R.MATICO,      
JRNL        AUTH 3 J.MOSLEY,A.NAYLOR,A.O'BRIEN,S.REDSHAW,P.ROWLAND,V.SOLEIL,    
JRNL        AUTH 4 K.J.SMITH,S.SWEITZER,P.THEOBALD,D.VESEY,D.S.WALTER,G.WAYNE   
JRNL        TITL   SECOND GENERATION OF BACE-1 INHIBITORS. PART 1: THE NEED FOR 
JRNL        TITL 2 IMPROVED PHARMACOKINETICS.                                   
JRNL        REF    BIOORG.MED.CHEM.LETT.         V.  19  3664 2009              
JRNL        REFN                   ISSN 0960-894X                               
JRNL        PMID   19428244                                                     
JRNL        DOI    10.1016/J.BMCL.2009.03.165                                   
REMARK   2                                                                      
REMARK   2 RESOLUTION.    1.60 ANGSTROMS.                                       
REMARK   3                                                                      
REMARK   3 REFINEMENT.                                                          
REMARK   3   PROGRAM     : CNS                                                  
REMARK   3   AUTHORS     : BRUNGER,ADAMS,CLORE,DELANO,GROS,GROSSE-              
REMARK   3               : KUNSTLEVE,JIANG,KUSZEWSKI,NILGES,PANNU,              
REMARK   3               : READ,RICE,SIMONSON,WARREN                            
REMARK   3                                                                      
REMARK   3  REFINEMENT TARGET : NULL                                            
REMARK   3                                                                      
REMARK   3  DATA USED IN REFINEMENT.                                            
REMARK   3   RESOLUTION RANGE HIGH (ANGSTROMS) : 1.60                           
REMARK   3   RESOLUTION RANGE LOW  (ANGSTROMS) : 23.00                          
REMARK   3   DATA CUTOFF            (SIGMA(F)) : NULL                           
REMARK   3   DATA CUTOFF HIGH         (ABS(F)) : NULL                           
REMARK   3   DATA CUTOFF LOW          (ABS(F)) : NULL                           
REMARK   3   COMPLETENESS (WORKING+TEST)   (%) : NULL                           
REMARK   3   NUMBER OF REFLECTIONS             : NULL                           
REMARK   3                                                                      
REMARK   3  FIT TO DATA USED IN REFINEMENT.                                     
REMARK   3   CROSS-VALIDATION METHOD          : NULL                            
REMARK   3   FREE R VALUE TEST SET SELECTION  : RANDOM                          
REMARK   3   R VALUE            (WORKING SET) : 0.188                           
REMARK   3   FREE R VALUE                     : 0.203                           
REMARK   3   FREE R VALUE TEST SET SIZE   (%) : 4.000                           
REMARK   3   FREE R VALUE TEST SET COUNT      : NULL                            
REMARK   3   ESTIMATED ERROR OF FREE R VALUE  : NULL                            
REMARK   3                                                                      
REMARK   3  FIT IN THE HIGHEST RESOLUTION BIN.                                  
REMARK   3   TOTAL NUMBER OF BINS USED           : NULL                         
REMARK   3   BIN RESOLUTION RANGE HIGH       (A) : NULL                         
REMARK   3   BIN RESOLUTION RANGE LOW        (A) : NULL                         
REMARK   3   BIN COMPLETENESS (WORKING+TEST) (%) : NULL                         
REMARK   3   REFLECTIONS IN BIN    (WORKING SET) : NULL                         
REMARK   3   BIN R VALUE           (WORKING SET) : NULL                         
REMARK   3   BIN FREE R VALUE                    : NULL                         
REMARK   3   BIN FREE R VALUE TEST SET SIZE  (%) : NULL                         
REMARK   3   BIN FREE R VALUE TEST SET COUNT     : NULL                         
REMARK   3   ESTIMATED ERROR OF BIN FREE R VALUE : NULL                         
REMARK   3                                                                      
REMARK   3  NUMBER OF NON-HYDROGEN ATOMS USED IN REFINEMENT.                    
REMARK   3   PROTEIN ATOMS            : 2934                                    
REMARK   3   NUCLEIC ACID ATOMS       : 0                                       
REMARK   3   HETEROGEN ATOMS          : 44                                      
REMARK   3   SOLVENT ATOMS            : 364                                     
REMARK   3                                                                      
REMARK   3  B VALUES.                                                           
REMARK   3   FROM WILSON PLOT           (A**2) : NULL                           
REMARK   3   MEAN B VALUE      (OVERALL, A**2) : NULL                           
REMARK   3   OVERALL ANISOTROPIC B VALUE.                                       
REMARK   3    B11 (A**2) : NULL                                                 
REMARK   3    B22 (A**2) : NULL                                                 
REMARK   3    B33 (A**2) : NULL                                                 
REMARK   3    B12 (A**2) : NULL                                                 
REMARK   3    B13 (A**2) : NULL                                                 
REMARK   3    B23 (A**2) : NULL                                                 
REMARK   3                                                                      
REMARK   3  ESTIMATED COORDINATE ERROR.                                         
REMARK   3   ESD FROM LUZZATI PLOT        (A) : NULL                            
REMARK   3   ESD FROM SIGMAA              (A) : NULL                            
REMARK   3   LOW RESOLUTION CUTOFF        (A) : NULL                            
REMARK   3                                                                      
REMARK   3  CROSS-VALIDATED ESTIMATED COORDINATE ERROR.                         
REMARK   3   ESD FROM C-V LUZZATI PLOT    (A) : NULL                            
REMARK   3   ESD FROM C-V SIGMAA          (A) : NULL                            
REMARK   3                                                                      
REMARK   3  RMS DEVIATIONS FROM IDEAL VALUES.                                   
REMARK   3   BOND LENGTHS                 (A) : NULL                            
REMARK   3   BOND ANGLES            (DEGREES) : NULL                            
REMARK   3   DIHEDRAL ANGLES        (DEGREES) : NULL                            
REMARK   3   IMPROPER ANGLES        (DEGREES) : NULL                            
REMARK   3                                                                      
REMARK   3  ISOTROPIC THERMAL MODEL : NULL                                      
REMARK   3                                                                      
REMARK   3  ISOTROPIC THERMAL FACTOR RESTRAINTS.    RMS    SIGMA                
REMARK   3   MAIN-CHAIN BOND              (A**2) : NULL  ; NULL                 
REMARK   3   MAIN-CHAIN ANGLE             (A**2) : NULL  ; NULL                 
REMARK   3   SIDE-CHAIN BOND              (A**2) : NULL  ; NULL                 
REMARK   3   SIDE-CHAIN ANGLE             (A**2) : NULL  ; NULL                 
REMARK   3                                                                      
REMARK   3  BULK SOLVENT MODELING.                                              
REMARK   3   METHOD USED : NULL                                                 
REMARK   3   KSOL        : NULL                                                 
REMARK   3   BSOL        : NULL                                                 
REMARK   3                                                                      
REMARK   3  NCS MODEL : NULL                                                    
REMARK   3                                                                      
REMARK   3  NCS RESTRAINTS.                         RMS   SIGMA/WEIGHT          
REMARK   3   GROUP  1  POSITIONAL            (A) : NULL  ; NULL                 
REMARK   3   GROUP  1  B-FACTOR           (A**2) : NULL  ; NULL                 
REMARK   3                                                                      
REMARK   3  PARAMETER FILE  1  : NULL                                           
REMARK   3  TOPOLOGY FILE  1   : NULL                                           
REMARK   3                                                                      
REMARK   3  OTHER REFINEMENT REMARKS: FULL DATA PROCESSING AND SCALING          
REMARK   3  STATISTICS NO LONGER AVAILABLE FOR THIS DATASET.                    
REMARK   4                                                                      
REMARK   4 2WF0 COMPLIES WITH FORMAT V. 3.30, 13-JUL-11                         
REMARK 100                                                                      
REMARK 100 THIS ENTRY HAS BEEN PROCESSED BY PDBE ON 02-APR-09.                  
REMARK 100 THE DEPOSITION ID IS D_1290039370.                                   
REMARK 200                                                                      
REMARK 200 EXPERIMENTAL DETAILS                                                 
REMARK 200  EXPERIMENT TYPE                : X-RAY DIFFRACTION                  
REMARK 200  DATE OF DATA COLLECTION        : NULL                               
REMARK 200  TEMPERATURE           (KELVIN) : 100                                
REMARK 200  PH                             : NULL                               
REMARK 200  NUMBER OF CRYSTALS USED        : 1                                  
REMARK 200                                                                      
REMARK 200  SYNCHROTRON              (Y/N) : Y                                  
REMARK 200  RADIATION SOURCE               : ESRF                               
REMARK 200  BEAMLINE                       : ID14-4                             
REMARK 200  X-RAY GENERATOR MODEL          : NULL                               
REMARK 200  MONOCHROMATIC OR LAUE    (M/L) : M                                  
REMARK 200  WAVELENGTH OR RANGE        (A) : 0.9393                             
REMARK 200  MONOCHROMATOR                  : NULL                               
REMARK 200  OPTICS                         : NULL                               
REMARK 200                                                                      
REMARK 200  DETECTOR TYPE                  : CCD                                
REMARK 200  DETECTOR MANUFACTURER          : ADSC CCD                           
REMARK 200  INTENSITY-INTEGRATION SOFTWARE : DENZO                              
REMARK 200  DATA SCALING SOFTWARE          : SCALEPACK                          
REMARK 200                                                                      
REMARK 200  NUMBER OF UNIQUE REFLECTIONS   : NULL                               
REMARK 200  RESOLUTION RANGE HIGH      (A) : NULL                               
REMARK 200  RESOLUTION RANGE LOW       (A) : NULL                               
REMARK 200  REJECTION CRITERIA  (SIGMA(I)) : NULL                               
REMARK 200                                                                      
REMARK 200 OVERALL.                                                             
REMARK 200  COMPLETENESS FOR RANGE     (%) : NULL                               
REMARK 200  DATA REDUNDANCY                : NULL                               
REMARK 200  R MERGE                    (I) : NULL                               
REMARK 200  R SYM                      (I) : NULL                               
REMARK 200  <I/SIGMA(I)> FOR THE DATA SET  : NULL                               
REMARK 200                                                                      
REMARK 200 IN THE HIGHEST RESOLUTION SHELL.                                     
REMARK 200  HIGHEST RESOLUTION SHELL, RANGE HIGH (A) : NULL                     
REMARK 200  HIGHEST RESOLUTION SHELL, RANGE LOW  (A) : NULL                     
REMARK 200  COMPLETENESS FOR SHELL     (%) : NULL                               
REMARK 200  DATA REDUNDANCY IN SHELL       : NULL                               
REMARK 200  R MERGE FOR SHELL          (I) : NULL                               
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: OTHER                        
REMARK 200 SOFTWARE USED: NULL                                                  
REMARK 200 STARTING MODEL: NONE                                                 
REMARK 200                                                                      
REMARK 200 REMARK: THIS DATASET WAS COLLECTED ON 4 FEB 2004                     
REMARK 280                                                                      
REMARK 280 CRYSTAL                                                              
REMARK 280 SOLVENT CONTENT, VS   (%): 38.96                                     
REMARK 280 MATTHEWS COEFFICIENT, VM (ANGSTROMS**3/DA): 2.03                     
REMARK 280                                                                      
REMARK 280 CRYSTALLIZATION CONDITIONS: CRYSTALS GROWN BY VAPOUR DIFFUSION AT    
REMARK 280  20C USING STREAK SEEDING, WITH 10% PEG8000 AND 0.1M GLYCINE PH      
REMARK 280  3.2, VAPOR DIFFUSION, TEMPERATURE 293K                              
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       24.18400            
REMARK 290   SMTRY2   2  0.000000 -1.000000  0.000000        0.00000            
REMARK 290   SMTRY3   2  0.000000  0.000000  1.000000       52.09150            
REMARK 290   SMTRY1   3 -1.000000  0.000000  0.000000        0.00000            
REMARK 290   SMTRY2   3  0.000000  1.000000  0.000000       38.35750            
REMARK 290   SMTRY3   3  0.000000  0.000000 -1.000000       52.09150            
REMARK 290   SMTRY1   4  1.000000  0.000000  0.000000       24.18400            
REMARK 290   SMTRY2   4  0.000000 -1.000000  0.000000       38.35750            
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: PQS                                                   
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 400                                                                      
REMARK 400 COMPOUND                                                             
REMARK 400 ENGINEERED RESIDUE IN CHAIN A, ASN 153 TO GLN                        
REMARK 400 ENGINEERED RESIDUE IN CHAIN A, ASN 172 TO GLN                        
REMARK 400 ENGINEERED RESIDUE IN CHAIN A, ASN 223 TO GLN                        
REMARK 400 ENGINEERED RESIDUE IN CHAIN A, ASN 354 TO GLN                        
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     VAL A    61                                                      
REMARK 465     GLY A   217                                                      
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     GLN 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     PRO A   448                                                      
REMARK 465     GLN A   449                                                      
REMARK 465     THR A   450                                                      
REMARK 465     ASP A   451                                                      
REMARK 465     GLU A   452                                                      
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     LEU A 438    CG   CD1  CD2                                       
REMARK 470     ILE A 447    CA   C    O    CB   CG1  CG2  CD1                   
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 169      -62.86   -100.17                                   
REMARK 500    TRP A 258      -81.00   -137.35                                   
REMARK 500    CYS A 420       52.52   -104.82                                   
REMARK 500    HIS A 423      147.16   -176.39                                   
REMARK 500    ASP A 424     -157.24   -114.86                                   
REMARK 500                                                                      
REMARK 500 REMARK: NULL                                                         
REMARK 525                                                                      
REMARK 525 SOLVENT                                                              
REMARK 525                                                                      
REMARK 525 THE SOLVENT MOLECULES HAVE CHAIN IDENTIFIERS THAT                    
REMARK 525 INDICATE THE POLYMER CHAIN WITH WHICH THEY ARE MOST                  
REMARK 525 CLOSELY ASSOCIATED. THE REMARK LISTS ALL THE SOLVENT                 
REMARK 525 MOLECULES WHICH ARE MORE THAN 5A AWAY FROM THE                       
REMARK 525 NEAREST POLYMER CHAIN (M = MODEL NUMBER;                             
REMARK 525 RES=RESIDUE NAME; C=CHAIN IDENTIFIER; SSEQ=SEQUENCE                  
REMARK 525 NUMBER; I=INSERTION CODE):                                           
REMARK 525                                                                      
REMARK 525  M RES CSSEQI                                                        
REMARK 525    HOH A2172        DISTANCE =  6.35 ANGSTROMS                       
REMARK 700                                                                      
REMARK 700 SHEET                                                                
REMARK 700 THE SHEET STRUCTURE OF THIS MOLECULE IS BIFURCATED. IN               
REMARK 700 ORDER TO REPRESENT THIS FEATURE IN THE SHEET RECORDS BELOW,          
REMARK 700 TWO SHEETS ARE DEFINED.                                              
REMARK 800                                                                      
REMARK 800 SITE                                                                 
REMARK 800 SITE_IDENTIFIER: AC1                                                 
REMARK 800 EVIDENCE_CODE: SOFTWARE                                              
REMARK 800 SITE_DESCRIPTION: BINDING SITE FOR RESIDUE ZY0 A 2000                
REMARK 900                                                                      
REMARK 900 RELATED ENTRIES                                                      
REMARK 900 RELATED ID: 1TQF   RELATED DB: PDB                                   
REMARK 900 CRYSTAL STRUCTURE OF HUMAN BETA SECRETASE COMPLEXED WITH L-124,671   
REMARK 900 RELATED ID: 1XN3   RELATED DB: PDB                                   
REMARK 900 CRYSTAL STRUCTURE OF BETA-SECRETASE BOUND TO A LONGINHIBITOR WITH    
REMARK 900 ADDITIONAL UPSTREAM RESIDUES.                                        
REMARK 900 RELATED ID: 2VNM   RELATED DB: PDB                                   
REMARK 900 HUMAN BACE-1 IN COMPLEX WITH 3-(1,1- DIOXIDOTETRAHYDRO-2H-1,2-       
REMARK 900 THIAZIN-2-YL)-5 -(ETHYLAMINO)-N-((1S,2R)-2-HYDROXY-1-( PHENYLMETHYL) 
REMARK 900 -3-(((3-(TRIFLUOROMETHYL)PHENYL) METHYL)AMINO)PROPYL)BENZAMIDE       
REMARK 900 RELATED ID: 1M4H   RELATED DB: PDB                                   
REMARK 900 CRYSTAL STRUCTURE OF BETA-SECRETASE COMPLEXED WITHINHIBITOR OM00-3   
REMARK 900 RELATED ID: 1XN2   RELATED DB: PDB                                   
REMARK 900 NEW SUBSTRATE BINDING POCKETS FOR BETA- SECRETASE.                   
REMARK 900 RELATED ID: 2FDP   RELATED DB: PDB                                   
REMARK 900 CRYSTAL STRUCTURE OF BETA-SECRETASE COMPLEXED WITH AN AMINO-         
REMARK 900 ETHYLENE INHIBITOR                                                   
REMARK 900 RELATED ID: 2VIY   RELATED DB: PDB                                   
REMARK 900 HUMAN BACE-1 IN COMPLEX WITH N-((1S,2R )-3-(((1S)-2-                 
REMARK 900 (CYCLOHEXYLAMINO)-1-METHYL-2- OXOETHYL)AMINO)-2-HYDROXY-1-           
REMARK 900 (PHENYLMETHYL) PROPYL)-3-(PENTYLSULFONYL)BENZAMIDE                   
REMARK 900 RELATED ID: 2VIE   RELATED DB: PDB                                   
REMARK 900 HUMAN BACE-1 IN COMPLEX WITH N-((1S,2R )-1-BENZYL-2-HYDROXY-3-((1,1, 
REMARK 900 5- TRIMETHYLHEXYL)AMINO)PROPYL)-3-(ETHYLAMINO)-5 -(2-OXOPYRROLIDIN-  
REMARK 900 1-YL)BENZAMIDE                                                       
REMARK 900 RELATED ID: 2VA6   RELATED DB: PDB                                   
REMARK 900 X-RAY CRYSTAL STRUCTURE OF BETA SECRETASE COMPLEXED WITH COMPOUND 24 
REMARK 900 RELATED ID: 2VJ6   RELATED DB: PDB                                   
REMARK 900 HUMAN BACE-1 IN COMPLEX WITH N-((1S,2R )-3-(((1S)-2-                 
REMARK 900 (CYCLOHEXYLAMINO)-1-METHYL-2- OXOETHYL)AMINO)-2-HYDROXY-1-           
REMARK 900 (PHENYLMETHYL) PROPYL)-3-(ETHYLAMINO)-5-(2-OXO-1- PYRROLIDINYL)      
REMARK 900 BENZAMIDE                                                            
REMARK 900 RELATED ID: 2VIZ   RELATED DB: PDB                                   
REMARK 900 HUMAN BACE-1 IN COMPLEX WITH N-((1S,2R )-3-(((1S)-2-                 
REMARK 900 (CYCLOHEXYLAMINO)-1-METHYL-2- OXOETHYL)AMINO)-2-HYDROXY-1-           
REMARK 900 (PHENYLMETHYL) PROPYL)-3-(2-OXO-1-PYRROLIDINYL)-5-( PROPYLOXY)       
REMARK 900 BENZAMIDE                                                            
REMARK 900 RELATED ID: 2B8L   RELATED DB: PDB                                   
REMARK 900 CRYSTAL STRUCTURE OF HUMAN BETA SECRETASE COMPLEXED WITH L-000384950 
REMARK 900 RELATED ID: 1YM4   RELATED DB: PDB                                   
REMARK 900 CRYSTAL STRUCTURE OF HUMAN BETA SECRETASE COMPLEXED WITHNVP-AMK640   
REMARK 900 RELATED ID: 1SGZ   RELATED DB: PDB                                   
REMARK 900 CRYSTAL STRUCTURE OF UNBOUND BETA-SECRETASE CATALYTICDOMAIN.         
REMARK 900 RELATED ID: 2VA5   RELATED DB: PDB                                   
REMARK 900 X-RAY CRYSTAL STRUCTURE OF BETA SECRETASE COMPLEXED WITH COMPOUND 8C 
REMARK 900 RELATED ID: 1UJK   RELATED DB: PDB                                   
REMARK 900 VHS DOMAIN OF HUMAN GGA1 COMPLEXED WITH C -TERMINALPHOSPHOPEPTIDE    
REMARK 900 FROM BACE                                                            
REMARK 900 RELATED ID: 2B8V   RELATED DB: PDB                                   
REMARK 900 CRYSTAL STRUCTURE OF HUMAN BETA-SECRETASE COMPLEXED WITH L-L000430,  
REMARK 900 469                                                                  
REMARK 900 RELATED ID: 1FKN   RELATED DB: PDB                                   
REMARK 900 STRUCTURE OF BETA-SECRETASE COMPLEXED WITH INHIBITOR                 
REMARK 900 RELATED ID: 1XS7   RELATED DB: PDB                                   
REMARK 900 CRYSTAL STRUCTURE OF A CYCLOAMIDE-URETHANE- DERIVED NOVELINHIBITOR   
REMARK 900 BOUND TO HUMAN BRAIN MEMAPSIN 2 (BETA-SECRETASE).                    
REMARK 900 RELATED ID: 2VIJ   RELATED DB: PDB                                   
REMARK 900 HUMAN BACE-1 IN COMPLEX WITH 3-(1,1- DIOXIDOTETRAHYDRO-2H-1,2-       
REMARK 900 THIAZIN-2-YL)-5 -(ETHYLAMINO)-N-((1S,2R)-2-HYDROXY-1-( PHENYLMETHYL) 
REMARK 900 -3-(1,2,3,4-TETRAHYDRO-1- NAPHTHALENYLAMINO)PROPYL)BENZAMIDE         
REMARK 900 RELATED ID: 2VA7   RELATED DB: PDB                                   
REMARK 900 X-RAY CRYSTAL STRUCTURE OF BETA SECRETASE COMPLEXED WITH COMPOUND 27 
REMARK 900 RELATED ID: 1YM2   RELATED DB: PDB                                   
REMARK 900 CRYSTAL STRUCTURE OF HUMAN BETA SECRETASE COMPLEXED WITHNVP-AUR200   
REMARK 900 RELATED ID: 2VJ9   RELATED DB: PDB                                   
REMARK 900 HUMAN BACE-1 IN COMPLEX WITH N-((1S,2R )-3-(CYCLOHEXYLAMINO)-2-      
REMARK 900 HYDROXY-1-( PHENYLMETHYL)PROPYL)-3-(ETHYLAMINO)-5-(2-OXO -1-         
REMARK 900 PYRROLIDINYL)BENZAMIDE                                               
REMARK 900 RELATED ID: 2VKM   RELATED DB: PDB                                   
REMARK 900 CRYSTAL STRUCTURE OF GRL-8234 BOUND TO BACE (BETA-SECRETASE)         
REMARK 900 RELATED ID: 2VNN   RELATED DB: PDB                                   
REMARK 900 HUMAN BACE-1 IN COMPLEX WITH 7-ETHYL-N -((1S,2R)-2-HYDROXY-1-        
REMARK 900 (PHENYLMETHYL)-3-((( 3-(TRIFLUOROMETHYL)PHENYL)METHYL)AMINO)PROPYL ) 
REMARK 900 -1-METHYL-3,4-DIHYDRO-1H-(1,2,5) THIADIAZEPINO(3,4,5-HI)INDOLE-9-    
REMARK 900 CARBOXAMIDE 2,2-DIOXIDE                                              
REMARK 900 RELATED ID: 1PY1   RELATED DB: PDB                                   
REMARK 900 COMPLEX OF GGA1-VHS DOMAIN AND BETA- SECRETASE C-                    
REMARK 900 TERMINALPHOSPHOPEPTIDE                                               
REMARK 900 RELATED ID: 1W50   RELATED DB: PDB                                   
REMARK 900 APO STRUCTURE OF BACE (BETA SECRETASE)                               
REMARK 900 RELATED ID: 1UJJ   RELATED DB: PDB                                   
REMARK 900 VHS DOMAIN OF HUMAN GGA1 COMPLEXED WITH C -TERMINAL PEPTIDEFROM BACE 
REMARK 900 RELATED ID: 2VJ7   RELATED DB: PDB                                   
REMARK 900 HUMAN BACE-1 IN COMPLEX WITH 3-(ETHYLAMINO )-N-((1S,2R)-2-HYDROXY-1- 
REMARK 900 (PHENYLMETHYL)-3 -(((3-(TRIFLUOROMETHYL)PHENYL)METHYL)AMINO) PROPYL) 
REMARK 900 -5-(2-OXO-1-PYRROLIDINYL)BENZAMIDE                                   
REMARK 900 RELATED ID: 1W51   RELATED DB: PDB                                   
REMARK 900 BACE (BETA SECRETASE) IN COMPLEX WITH A NANOMOLAR NON-PEPTIDIC       
REMARK 900 INHIBITOR                                                            
REMARK 900 RELATED ID: 2WF3   RELATED DB: PDB                                   
REMARK 900 HUMAN BACE-1 IN COMPLEX WITH 6-(ETHYLAMINO )-N-((1S,2R)-2-HYDROXY-3- 
REMARK 900 (((3-(METHYLOXY )PHENYL)METHYL)AMINO)-1-(PHENYLMETHYL)PROPYL )-1-    
REMARK 900 METHYL-1,3,4,5-TETRAHYDRO-2,1- BENZOTHIAZEPINE-8-CARBOXAMIDE 2,2-    
REMARK 900 DIOXIDE                                                              
REMARK 900 RELATED ID: 2WF1   RELATED DB: PDB                                   
REMARK 900 HUMAN BACE-1 IN COMPLEX WITH 7-ETHYL-N -((1S,2R)-2-HYDROXY-3-(((3-   
REMARK 900 (METHYLOXY) PHENYL(METHYL)AMINO)-1-(PHENYLMETHYL)PROPYL)- 1-METHYL-  
REMARK 900 3,4-DIHYDRO-1H-(1,2,5) THIADIAZEPINO(3,4,5-HI)INDOLE-9- CARBOXAMIDE  
REMARK 900 2,2-DIOXIDE                                                          
REMARK 900 RELATED ID: 2WF4   RELATED DB: PDB                                   
REMARK 900 HUMAN BACE-1 IN COMPLEX WITH 6-ETHYL-1- METHYL-N-((1S)-2-OXO-1-      
REMARK 900 (PHENYLMETHYL)-3-( TETRAHYDRO-2H-PYRAN-4-YLAMINO)PROPYL)-1,3 ,4,6-   
REMARK 900 TETRAHYDRO(1,2)THIAZEPINO(5,4,3- CD)INDOLE-8-CARBOXAMIDE 2,2-DIOXIDE 
REMARK 900 RELATED ID: 2WEZ   RELATED DB: PDB                                   
REMARK 900 HUMAN BACE-1 IN COMPLEX WITH 1-ETHYL-N -((1S,2R)-2-HYDROXY-3-(((3-   
REMARK 900 (METHYLOXY) PHENYL)METHYL)AMINO)-1-(PHENYLMETHYL)PROPYL)- 4-(2-OXO-  
REMARK 900 1-PYRROLIDINYL)-1H-INDOLE-6- CARBOXAMIDE                             
REMARK 900 RELATED ID: 2WF2   RELATED DB: PDB                                   
REMARK 900 HUMAN BACE-1 IN COMPLEX WITH 8-ETHYL-N -((1S,2R)-2-HYDROXY-3-(((3-   
REMARK 900 (METHYLOXY) PHENYL)METHYL)AMINO)-1-(PHENYLMETHYL)PROPYL)- 1-METHYL-  
REMARK 900 3,4,7,8-TETRAHYDRO-1H,6H-(1, 2,5)THIADIAZEPINO(5,4,3-DE)QUINOXALINE- 
REMARK 900 10-CARBOXAMIDE 2,2-DIOXIDE                                           
DBREF  2WF0 A   61   452  UNP    P56817   BACE1_HUMAN     61    452             
SEQADV 2WF0 GLN A  153  UNP  P56817    ASN   153 ENGINEERED MUTATION            
SEQADV 2WF0 GLN A  172  UNP  P56817    ASN   172 ENGINEERED MUTATION            
SEQADV 2WF0 GLN A  223  UNP  P56817    ASN   223 ENGINEERED MUTATION            
SEQADV 2WF0 GLN A  354  UNP  P56817    ASN   354 ENGINEERED MUTATION            
SEQRES   1 A  392  VAL GLU MET VAL ASP ASN LEU ARG GLY LYS SER GLY GLN          
SEQRES   2 A  392  GLY TYR TYR VAL GLU MET THR VAL GLY SER PRO PRO GLN          
SEQRES   3 A  392  THR LEU ASN ILE LEU VAL ASP THR GLY SER SER ASN PHE          
SEQRES   4 A  392  ALA VAL GLY ALA ALA PRO HIS PRO PHE LEU HIS ARG TYR          
SEQRES   5 A  392  TYR GLN ARG GLN LEU SER SER THR TYR ARG ASP LEU ARG          
SEQRES   6 A  392  LYS GLY VAL TYR VAL PRO TYR THR GLN GLY LYS TRP GLU          
SEQRES   7 A  392  GLY GLU LEU GLY THR ASP LEU VAL SER ILE PRO HIS GLY          
SEQRES   8 A  392  PRO GLN VAL THR VAL ARG ALA ASN ILE ALA ALA ILE THR          
SEQRES   9 A  392  GLU SER ASP LYS PHE PHE ILE GLN GLY SER ASN TRP GLU          
SEQRES  10 A  392  GLY ILE LEU GLY LEU ALA TYR ALA GLU ILE ALA ARG PRO          
SEQRES  11 A  392  ASP ASP SER LEU GLU PRO PHE PHE ASP SER LEU VAL LYS          
SEQRES  12 A  392  GLN THR HIS VAL PRO ASN LEU PHE SER LEU GLN LEU CYS          
SEQRES  13 A  392  GLY ALA GLY PHE PRO LEU GLN GLN SER GLU VAL LEU ALA          
SEQRES  14 A  392  SER VAL GLY GLY SER MET ILE ILE GLY GLY ILE ASP HIS          
SEQRES  15 A  392  SER LEU TYR THR GLY SER LEU TRP TYR THR PRO ILE ARG          
SEQRES  16 A  392  ARG GLU TRP TYR TYR GLU VAL ILE ILE VAL ARG VAL GLU          
SEQRES  17 A  392  ILE ASN GLY GLN ASP LEU LYS MET ASP CYS LYS GLU TYR          
SEQRES  18 A  392  ASN TYR ASP LYS SER ILE VAL ASP SER GLY THR THR ASN          
SEQRES  19 A  392  LEU ARG LEU PRO LYS LYS VAL PHE GLU ALA ALA VAL LYS          
SEQRES  20 A  392  SER ILE LYS ALA ALA SER SER THR GLU LYS PHE PRO ASP          
SEQRES  21 A  392  GLY PHE TRP LEU GLY GLU GLN LEU VAL CYS TRP GLN ALA          
SEQRES  22 A  392  GLY THR THR PRO TRP ASN ILE PHE PRO VAL ILE SER LEU          
SEQRES  23 A  392  TYR LEU MET GLY GLU VAL THR GLN GLN SER PHE ARG ILE          
SEQRES  24 A  392  THR ILE LEU PRO GLN GLN TYR LEU ARG PRO VAL GLU ASP          
SEQRES  25 A  392  VAL ALA THR SER GLN ASP ASP CYS TYR LYS PHE ALA ILE          
SEQRES  26 A  392  SER GLN SER SER THR GLY THR VAL MET GLY ALA VAL ILE          
SEQRES  27 A  392  MET GLU GLY PHE TYR VAL VAL PHE ASP ARG ALA ARG LYS          
SEQRES  28 A  392  ARG ILE GLY PHE ALA VAL SER ALA CYS HIS VAL HIS ASP          
SEQRES  29 A  392  GLU PHE ARG THR ALA ALA VAL GLU GLY PRO PHE VAL THR          
SEQRES  30 A  392  LEU ASP MET GLU ASP CYS GLY TYR ASN ILE PRO GLN THR          
SEQRES  31 A  392  ASP GLU                                                      
HET    ZY0  A2000      44                                                       
HETNAM     ZY0 N-[(1S,2R)-1-BENZYL-2-HYDROXY-3-{[3-(TRIFLUOROMETHYL)            
HETNAM   2 ZY0  BENZYL]AMINO}PROPYL]-4-ETHYL-8-(2-OXOPYRROLIDIN-1-YL)           
HETNAM   3 ZY0  QUINOLINE-6-CARBOXAMIDE                                         
FORMUL   2  ZY0    C34 H35 F3 N4 O3                                             
FORMUL   3  HOH   *364(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  313  1                                  15    
HELIX    7   7 PRO A  319  LEU A  324  1                                   6    
HELIX    8   8 PRO A  337  PHE A  341  5                                   5    
HELIX    9   9 LEU A  362  TYR A  366  1                                   5    
HELIX   10  10 ASP A  372  SER A  376  5                                   5    
HELIX   11  11 GLY A  395  GLU A  400  1                                   6    
SHEET    1  AA 3 ARG A 122  PRO A 131  0                                        
SHEET    2  AA 3 LYS A 136  SER A 147 -1  O  TRP A 137   N  VAL A 130           
SHEET    3  AA 3 TYR A  75  VAL A  81 -1  O  THR A  80   N  SER A 147           
SHEET    1  AB 7 ARG A 122  PRO A 131  0                                        
SHEET    2  AB 7 LYS A 136  SER A 147 -1  O  TRP A 137   N  VAL A 130           
SHEET    3  AB 7 THR A 155  ASP A 167 -1  O  VAL A 156   N  VAL A 146           
SHEET    4  AB 7 PHE A  99  GLY A 102  1  O  PHE A  99   N  ALA A 161           
SHEET    5  AB 7 GLY A 178  GLY A 181 -1  O  ILE A 179   N  ALA A 100           
SHEET    6  AB 7 GLN A  86  ASP A  93  1  O  LEU A  91   N  LEU A 180           
SHEET    7  AB 7 TYR A  75  VAL A  81 -1  O  TYR A  75   N  VAL A  92           
SHEET    1  AC 5 GLN A 272  ASP A 273  0                                        
SHEET    2  AC 5 ILE A 264  ILE A 269 -1  O  ILE A 269   N  GLN A 272           
SHEET    3  AC 5 ILE A 344  MET A 349 -1  O  SER A 345   N  GLU A 268           
SHEET    4  AC 5 GLN A 355  ILE A 361 -1  O  PHE A 357   N  LEU A 348           
SHEET    5  AC 5 ALA A 430  VAL A 436 -1  O  ALA A 430   N  THR A 360           
SHEET    1  AD 4 SER A 286  VAL A 288  0                                        
SHEET    2  AD 4 THR A 392  MET A 394  1  O  THR A 392   N  ILE A 287           
SHEET    3  AD 4 LEU A 295  PRO A 298 -1  O  ARG A 296   N  VAL A 393           
SHEET    4  AD 4 ILE A 385  SER A 388  1  O  SER A 386   N  LEU A 297           
SHEET    1  AE 3 VAL A 329  GLN A 332  0                                        
SHEET    2  AE 3 ASP A 378  PHE A 383 -1  O  ASP A 379   N  TRP A 331           
SHEET    3  AE 3 LEU A 367  PRO A 369 -1  O  ARG A 368   N  LYS A 382           
SSBOND   1 CYS A  216    CYS A  420                          1555   1555  2.04  
SSBOND   2 CYS A  278    CYS A  443                          1555   1555  2.03  
SSBOND   3 CYS A  330    CYS A  380                          1555   1555  2.04  
CISPEP   1 SER A   83    PRO A   84          0        -3.22                     
CISPEP   2 SER A   83    PRO A   84          0         0.16                     
CISPEP   3 ARG A  189    PRO A  190          0         3.57                     
CISPEP   4 TYR A  283    ASP A  284          0         1.89                     
CISPEP   5 GLY A  433    PRO A  434          0        -1.64                     
SITE     1 AC1 19 GLY A  72  GLN A  73  GLY A  74  ASP A  93                    
SITE     2 AC1 19 GLY A  95  SER A  96  PRO A 131  TYR A 132                    
SITE     3 AC1 19 THR A 133  GLN A 134  PHE A 169  TRP A 176                    
SITE     4 AC1 19 ARG A 189  ASP A 289  GLY A 291  THR A 292                    
SITE     5 AC1 19 THR A 293  ASN A 294  HOH A2364                               
CRYST1   48.368   76.715  104.183  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      0.020675  0.000000  0.000000        0.00000                         
SCALE2      0.000000  0.013035  0.000000        0.00000                         
SCALE3      0.000000  0.000000  0.009598        0.00000                         
(ATOM LINES ARE NOT SHOWN.)
END                                                                             
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