HEADER HYDROLASE 06-DEC-07 2VJ7
TITLE HUMAN BACE-1 IN COMPLEX WITH 3-(ETHYLAMINO)-N-((1S,2R)-2-HYDROXY-1-
TITLE 2 (PHENYLMETHYL)-3-(((3-(TRIFLUOROMETHYL)PHENYL)METHYL)AMINO)PROPYL)-5-
TITLE 3 (2-OXO-1-PYRROLIDINYL)BENZAMIDE
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 APP CLEAVING ENZYME 1, BETA-SITE AMYLOID PRECURSOR
COMPND 6 PROTEIN CLEAVING ENZYME 1, MEMBRANE-ASSOCIATED ASPARTIC PROTEASE 2,
COMPND 7 MEMAPSIN-2, ASPARTYL PROTEASE 2, 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_TAXID: 10029;
SOURCE 7 EXPRESSION_SYSTEM_TISSUE: OVARY
KEYWDS ALTERNATIVE SPLICING, BETA-SITE APP CLEAVING ENZYME, BETA-SECRETASE,
KEYWDS 2 ASPARTYL PROTEASE, ASP-2, BACE-1, ZYMOGEN, PROTEASE, MEMBRANE,
KEYWDS 3 HYDROLASE, MEMAPSIN-2, GLYCOPROTEIN, TRANSMEMBRANE
EXPDTA X-RAY DIFFRACTION
AUTHOR B.CLARKE,E.DEMONT,C.DINGWALL,R.DUNSDON,A.FALLER,J.HAWKINS,I.HUSSAIN,
AUTHOR 2 D.MACPHERSON,G.MAILE,R.MATICO,P.MILNER,J.MOSLEY,A.NAYLOR,A.O'BRIEN,
AUTHOR 3 S.REDSHAW,D.RIDDELL,P.ROWLAND,V.SOLEIL,K.SMITH,S.STANWAY,G.STEMP,
AUTHOR 4 S.SWEITZER,P.THEOBALD,D.VESEY,D.S.WALTER,J.WARD,G.WAYNE
REVDAT 5 15-MAY-19 2VJ7 1 REMARK
REVDAT 4 06-MAR-19 2VJ7 1 REMARK
REVDAT 3 24-FEB-09 2VJ7 1 VERSN
REVDAT 2 19-FEB-08 2VJ7 1 JRNL
REVDAT 1 29-JAN-08 2VJ7 0
JRNL AUTH B.CLARKE,E.DEMONT,C.DINGWALL,R.DUNSDON,A.FALLER,J.HAWKINS,
JRNL AUTH 2 I.HUSSAIN,D.MACPHERSON,G.MAILE,R.MATICO,P.MILNER,J.MOSLEY,
JRNL AUTH 3 A.NAYLOR,A.O'BRIEN,S.REDSHAW,D.RIDDELL,P.ROWLAND,V.SOLEIL,
JRNL AUTH 4 K.SMITH,S.STANWAY,G.STEMP,S.SWEITZER,P.THEOBALD,D.VESEY,
JRNL AUTH 5 D.S.WALTER,J.WARD,G.WAYNE
JRNL TITL BACE-1 INHIBITORS PART 2: IDENTIFICATION OF HYDROXY
JRNL TITL 2 ETHYLAMINES (HEAS) WITH REDUCED PEPTIDIC CHARACTER.
JRNL REF BIOORG.MED.CHEM.LETT. V. 18 1017 2008
JRNL REFN ISSN 0960-894X
JRNL PMID 18166458
JRNL DOI 10.1016/J.BMCL.2007.12.019
REMARK 2
REMARK 2 RESOLUTION. 1.60 ANGSTROMS.
REMARK 3
REMARK 3 REFINEMENT.
REMARK 3 PROGRAM : CNX 2000
REMARK 3 AUTHORS : BRUNGER,ADAMS,CLORE,DELANO,GROS,GROSSE-
REMARK 3 : KUNSTLEVE,JIANG,KUSZEWSKI,NILGES,PANNU,
REMARK 3 : READ,RICE,SIMONSON,WARREN,ACCELRYS
REMARK 3 : SOFTWARE INC.(BADGER,BERARD,KUMAR,SZALMA,
REMARK 3 : YIP,DZAKULA)
REMARK 3
REMARK 3 DATA USED IN REFINEMENT.
REMARK 3 RESOLUTION RANGE HIGH (ANGSTROMS) : 1.60
REMARK 3 RESOLUTION RANGE LOW (ANGSTROMS) : 25.00
REMARK 3 DATA CUTOFF (SIGMA(F)) : 0.000
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 : 48694
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) : 0.209
REMARK 3 R VALUE (WORKING SET) : 0.209
REMARK 3 FREE R VALUE : 0.231
REMARK 3 FREE R VALUE TEST SET SIZE (%) : 4.000
REMARK 3 FREE R VALUE TEST SET COUNT : 1951
REMARK 3 ESTIMATED ERROR OF FREE R VALUE : 0.005
REMARK 3
REMARK 3 FIT/AGREEMENT OF MODEL WITH ALL DATA.
REMARK 3 R VALUE (WORKING + TEST SET, NO CUTOFF) : NULL
REMARK 3 R VALUE (WORKING SET, NO CUTOFF) : NULL
REMARK 3 FREE R VALUE (NO CUTOFF) : NULL
REMARK 3 FREE R VALUE TEST SET SIZE (%, NO CUTOFF) : NULL
REMARK 3 FREE R VALUE TEST SET COUNT (NO CUTOFF) : NULL
REMARK 3 ESTIMATED ERROR OF FREE R VALUE (NO CUTOFF) : NULL
REMARK 3 TOTAL NUMBER OF REFLECTIONS (NO CUTOFF) : NULL
REMARK 3
REMARK 3 FIT IN THE HIGHEST RESOLUTION BIN.
REMARK 3 TOTAL NUMBER OF BINS USED : 39
REMARK 3 BIN RESOLUTION RANGE HIGH (A) : 1.60
REMARK 3 BIN RESOLUTION RANGE LOW (A) : 1.63
REMARK 3 BIN COMPLETENESS (WORKING+TEST) (%) : NULL
REMARK 3 REFLECTIONS IN BIN (WORKING SET) : NULL
REMARK 3 BIN R VALUE (WORKING SET) : 0.2550
REMARK 3 BIN FREE R VALUE : 0.3040
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 : 0.045
REMARK 3
REMARK 3 NUMBER OF NON-HYDROGEN ATOMS USED IN REFINEMENT.
REMARK 3 PROTEIN ATOMS : 2921
REMARK 3 NUCLEIC ACID ATOMS : 0
REMARK 3 HETEROGEN ATOMS : 41
REMARK 3 SOLVENT ATOMS : 333
REMARK 3
REMARK 3 B VALUES.
REMARK 3 FROM WILSON PLOT (A**2) : 18.10
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) : 0.005
REMARK 3 BOND ANGLES (DEGREES) : 0.900
REMARK 3 DIHEDRAL ANGLES (DEGREES) : NULL
REMARK 3 IMPROPER ANGLES (DEGREES) : NULL
REMARK 3
REMARK 3 ISOTROPIC THERMAL MODEL : RESTRAINED
REMARK 3
REMARK 3 ISOTROPIC THERMAL FACTOR RESTRAINTS. RMS SIGMA
REMARK 3 MAIN-CHAIN BOND (A**2) : 1.250 ; 1.500
REMARK 3 MAIN-CHAIN ANGLE (A**2) : 1.970 ; 2.000
REMARK 3 SIDE-CHAIN BOND (A**2) : 1.970 ; 2.000
REMARK 3 SIDE-CHAIN ANGLE (A**2) : 2.930 ; 2.500
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: NULL
REMARK 4
REMARK 4 2VJ7 COMPLIES WITH FORMAT V. 3.30, 13-JUL-11
REMARK 100
REMARK 100 THIS ENTRY HAS BEEN PROCESSED BY PDBE ON 06-DEC-07.
REMARK 100 THE DEPOSITION ID IS D_1290034704.
REMARK 200
REMARK 200 EXPERIMENTAL DETAILS
REMARK 200 EXPERIMENT TYPE : X-RAY DIFFRACTION
REMARK 200 DATE OF DATA COLLECTION : 10-JUL-02
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
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 : 48870
REMARK 200 RESOLUTION RANGE HIGH (A) : 1.600
REMARK 200 RESOLUTION RANGE LOW (A) : 25.000
REMARK 200 REJECTION CRITERIA (SIGMA(I)) : 0.000
REMARK 200
REMARK 200 OVERALL.
REMARK 200 COMPLETENESS FOR RANGE (%) : 93.3
REMARK 200 DATA REDUNDANCY : 4.700
REMARK 200 R MERGE (I) : 0.05000
REMARK 200 R SYM (I) : NULL
REMARK 200 <I/SIGMA(I)> FOR THE DATA SET : 24.9000
REMARK 200
REMARK 200 IN THE HIGHEST RESOLUTION SHELL.
REMARK 200 HIGHEST RESOLUTION SHELL, RANGE HIGH (A) : 1.60
REMARK 200 HIGHEST RESOLUTION SHELL, RANGE LOW (A) : 1.63
REMARK 200 COMPLETENESS FOR SHELL (%) : 86.5
REMARK 200 DATA REDUNDANCY IN SHELL : NULL
REMARK 200 R MERGE FOR SHELL (I) : 0.24000
REMARK 200 R SYM FOR SHELL (I) : NULL
REMARK 200 <I/SIGMA(I)> FOR SHELL : 3.600
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: NONE
REMARK 280
REMARK 280 CRYSTAL
REMARK 280 SOLVENT CONTENT, VS (%): 41.03
REMARK 280 MATTHEWS COEFFICIENT, VM (ANGSTROMS**3/DA): 2.10
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 24.16750
REMARK 290 SMTRY2 2 0.000000 -1.000000 0.000000 0.00000
REMARK 290 SMTRY3 2 0.000000 0.000000 1.000000 51.96400
REMARK 290 SMTRY1 3 -1.000000 0.000000 0.000000 0.00000
REMARK 290 SMTRY2 3 0.000000 1.000000 0.000000 38.60700
REMARK 290 SMTRY3 3 0.000000 0.000000 -1.000000 51.96400
REMARK 290 SMTRY1 4 1.000000 0.000000 0.000000 24.16750
REMARK 290 SMTRY2 4 0.000000 -1.000000 0.000000 38.60700
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 SER A 230
REMARK 465 VAL A 231
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 -63.00 -101.27
REMARK 500 TRP A 258 -81.02 -137.36
REMARK 500 ASP A 372 112.45 -161.27
REMARK 500 ASN A 446 -170.06 88.07
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 A2043 DISTANCE = 6.20 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 VG6 A1448
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: 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: 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: 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: 2VA5 RELATED DB: PDB
REMARK 900 X-RAY CRYSTAL STRUCTURE OF BETA SECRETASE COMPLEXED WITH COMPOUND 8C
REMARK 900 RELATED ID: 1SGZ RELATED DB: PDB
REMARK 900 CRYSTAL STRUCTURE OF UNBOUND BETA-SECRETASE CATALYTICDOMAIN.
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: 1UJK RELATED DB: PDB
REMARK 900 VHS DOMAIN OF HUMAN GGA1 COMPLEXED WITH C -TERMINALPHOSPHOPEPTIDE
REMARK 900 FROM BACE
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: 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: 1W51 RELATED DB: PDB
REMARK 900 BACE (BETA SECRETASE) IN COMPLEX WITH A NANOMOLAR NON-PEPTIDIC
REMARK 900 INHIBITOR
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
DBREF 2VJ7 A 61 452 UNP P56817 BACE1_HUMAN 61 452
SEQADV 2VJ7 GLN A 153 UNP P56817 ASN 153 ENGINEERED MUTATION
SEQADV 2VJ7 GLN A 172 UNP P56817 ASN 172 ENGINEERED MUTATION
SEQADV 2VJ7 GLN A 223 UNP P56817 ASN 223 ENGINEERED MUTATION
SEQADV 2VJ7 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 VG6 A1448 41
HETNAM VG6 N-[(1S,2R)-1-BENZYL-2-HYDROXY-3-{[3-(TRIFLUOROMETHYL)
HETNAM 2 VG6 BENZYL]AMINO}PROPYL]-3-(ETHYLAMINO)-5-(2-
HETNAM 3 VG6 OXOPYRROLIDIN-1-YL)BENZAMIDE
FORMUL 2 VG6 C31 H35 F3 N4 O3
FORMUL 3 HOH *333(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 7 LEU A 67 GLY A 69 0
SHEET 2 AA 7 TYR A 75 VAL A 81 -1 O TYR A 76 N ARG A 68
SHEET 3 AA 7 GLN A 86 ASP A 93 -1 O GLN A 86 N VAL A 81
SHEET 4 AA 7 GLY A 178 GLY A 181 1 O GLY A 178 N LEU A 91
SHEET 5 AA 7 PHE A 99 GLY A 102 -1 O ALA A 100 N ILE A 179
SHEET 6 AA 7 THR A 155 ASP A 167 1 O ALA A 161 N VAL A 101
SHEET 7 AA 7 LYS A 136 SER A 147 -1 O LYS A 136 N ASP A 167
SHEET 1 AB 3 LEU A 67 GLY A 69 0
SHEET 2 AB 3 TYR A 75 VAL A 81 -1 O TYR A 76 N ARG A 68
SHEET 3 AB 3 LYS A 136 SER A 147 -1 O SER A 147 N THR A 80
SHEET 1 AC 5 GLY A 233 ILE A 237 0
SHEET 2 AC 5 PHE A 211 LEU A 215 -1 O SER A 212 N ILE A 236
SHEET 3 AC 5 PHE A 402 ASP A 407 -1 O PHE A 402 N LEU A 215
SHEET 4 AC 5 ARG A 412 SER A 418 -1 O ARG A 412 N ASP A 407
SHEET 5 AC 5 TYR A 245 PRO A 253 -1 O THR A 246 N VAL A 417
SHEET 1 AD 5 GLN A 272 ASP A 273 0
SHEET 2 AD 5 ILE A 264 ILE A 269 -1 O ILE A 269 N GLN A 272
SHEET 3 AD 5 ILE A 344 MET A 349 -1 O SER A 345 N GLU A 268
SHEET 4 AD 5 GLN A 355 ILE A 361 -1 O PHE A 357 N LEU A 348
SHEET 5 AD 5 ALA A 430 VAL A 436 -1 O ALA A 430 N THR A 360
SHEET 1 AE 4 SER A 286 VAL A 288 0
SHEET 2 AE 4 THR A 392 MET A 394 1 O THR A 392 N ILE A 287
SHEET 3 AE 4 LEU A 295 PRO A 298 -1 O ARG A 296 N VAL A 393
SHEET 4 AE 4 ILE A 385 SER A 388 1 O SER A 386 N LEU A 297
SHEET 1 AF 3 VAL A 329 GLN A 332 0
SHEET 2 AF 3 ASP A 378 PHE A 383 -1 O ASP A 379 N TRP A 331
SHEET 3 AF 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 2.03
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 -3.78
CISPEP 2 ARG A 189 PRO A 190 0 0.70
CISPEP 3 TYR A 283 ASP A 284 0 -0.36
CISPEP 4 GLY A 433 PRO A 434 0 -0.12
SITE 1 AC1 18 GLN A 73 GLY A 74 LEU A 91 ASP A 93
SITE 2 AC1 18 GLY A 95 SER A 96 VAL A 130 PRO A 131
SITE 3 AC1 18 TYR A 132 THR A 133 GLN A 134 PHE A 169
SITE 4 AC1 18 ASP A 289 GLY A 291 THR A 292 THR A 293
SITE 5 AC1 18 ASN A 294 SER A 386
CRYST1 48.335 77.214 103.928 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 0.020689 0.000000 0.000000 0.00000
SCALE2 0.000000 0.012951 0.000000 0.00000
SCALE3 0.000000 0.000000 0.009622 0.00000
(ATOM LINES ARE NOT SHOWN.)
END