HEADER HYDROLASE 24-MAY-10 2XFI
TITLE HUMAN BACE-1 IN COMPLEX WITH N-((1S,2R)-3-(((1S)-2-(CYCLOHEXYLAMINO)-
TITLE 2 1-METHYL-2-OXOETHYL)AMINO)-2-HYDROXY-1-(PHENYLMETHYL)PROPYL)-3-
TITLE 3 ((METHYLSULFONYL)(PHENYL)AMINO)BENZAMIDE
COMPND MOL_ID: 1;
COMPND 2 MOLECULE: BETA-SECRETASE 1;
COMPND 3 CHAIN: A;
COMPND 4 FRAGMENT: RESIDUES 61-452;
COMPND 5 SYNONYM: BACE-1, BETA-SITE AMYLOID PRECURSOR PROTEIN CLEAVING ENZYME
COMPND 6 1, BETA-SITE APP CLEAVING ENZYME 1, MEMBRANE-ASSOCIATED ASPARTIC
COMPND 7 PROTEASE 2, MEMAPSIN-2, ASPARTYL PROTEASE 2, ASP2, ASP 2;
COMPND 8 EC: 3.4.23.46;
COMPND 9 ENGINEERED: YES;
COMPND 10 MUTATION: YES
SOURCE MOL_ID: 1;
SOURCE 2 ORGANISM_SCIENTIFIC: HOMO SAPIENS;
SOURCE 3 ORGANISM_COMMON: HUMAN;
SOURCE 4 ORGANISM_TAXID: 9606;
SOURCE 5 EXPRESSION_SYSTEM: CRICETULUS GRISEUS;
SOURCE 6 EXPRESSION_SYSTEM_COMMON: CHINESE HAMSTER;
SOURCE 7 EXPRESSION_SYSTEM_TAXID: 10029;
SOURCE 8 EXPRESSION_SYSTEM_TISSUE: OVARY
KEYWDS HYDROLASE, PROTEASE, ZYMOGEN
EXPDTA X-RAY DIFFRACTION
AUTHOR B.CLARKE,L.CUTLER,E.DEMONT,C.DINGWALL,R.DUNSDON,J.HAWKINS,C.HOWES,
AUTHOR 2 I.HUSSAIN,G.MAILE,R.MATICO,J.MOSLEY,A.NAYLOR,A.O'BRIEN,S.REDSHAW,
AUTHOR 3 P.ROWLAND,V.SOLEIL,K.J.SMITH,S.SWEITZER,P.THEOBALD,D.VESEY,
AUTHOR 4 D.S.WALTER,G.WAYNE
REVDAT 4 15-MAY-19 2XFI 1 REMARK
REVDAT 3 06-MAR-19 2XFI 1 REMARK
REVDAT 2 28-JUL-10 2XFI 1 JRNL
REVDAT 1 07-JUL-10 2XFI 0
JRNL AUTH B.CLARKE,L.CUTLER,E.DEMONT,C.DINGWALL,R.DUNSDON,J.HAWKINS,
JRNL AUTH 2 C.HOWES,I.HUSSAIN,G.MAILE,R.MATICO,J.MOSLEY,A.NAYLOR,
JRNL AUTH 3 A.O'BRIEN,S.REDSHAW,P.ROWLAND,V.SOLEIL,K.J.SMITH,S.SWEITZER,
JRNL AUTH 4 P.THEOBALD,D.VESEY,D.S.WALTER,G.WAYNE
JRNL TITL BACE-1 INHIBITORS USING NOVEL EDGE-TO-FACE INTERACTION WITH
JRNL TITL 2 ARG-296
JRNL REF BIOORG.MED.CHEM.LETT. V. 20 4639 2010
JRNL REFN ISSN 0960-894X
JRNL PMID 20579874
JRNL DOI 10.1016/J.BMCL.2010.05.111
REMARK 2
REMARK 2 RESOLUTION. 1.73 ANGSTROMS.
REMARK 3
REMARK 3 REFINEMENT.
REMARK 3 PROGRAM : REFMAC 5.5.0109
REMARK 3 AUTHORS : MURSHUDOV,SKUBAK,LEBEDEV,PANNU,STEINER,
REMARK 3 : NICHOLLS,WINN,LONG,VAGIN
REMARK 3
REMARK 3 REFINEMENT TARGET : MAXIMUM LIKELIHOOD
REMARK 3
REMARK 3 DATA USED IN REFINEMENT.
REMARK 3 RESOLUTION RANGE HIGH (ANGSTROMS) : 1.73
REMARK 3 RESOLUTION RANGE LOW (ANGSTROMS) : 62.01
REMARK 3 DATA CUTOFF (SIGMA(F)) : NULL
REMARK 3 COMPLETENESS FOR RANGE (%) : 97.1
REMARK 3 NUMBER OF REFLECTIONS : 38878
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) : 0.172
REMARK 3 R VALUE (WORKING SET) : 0.171
REMARK 3 FREE R VALUE : 0.198
REMARK 3 FREE R VALUE TEST SET SIZE (%) : 4.000
REMARK 3 FREE R VALUE TEST SET COUNT : 1628
REMARK 3
REMARK 3 FIT IN THE HIGHEST RESOLUTION BIN.
REMARK 3 TOTAL NUMBER OF BINS USED : 20
REMARK 3 BIN RESOLUTION RANGE HIGH (A) : 1.73
REMARK 3 BIN RESOLUTION RANGE LOW (A) : 1.77
REMARK 3 REFLECTION IN BIN (WORKING SET) : 2258
REMARK 3 BIN COMPLETENESS (WORKING+TEST) (%) : 77.84
REMARK 3 BIN R VALUE (WORKING SET) : 0.1880
REMARK 3 BIN FREE R VALUE SET COUNT : 95
REMARK 3 BIN FREE R VALUE : 0.2170
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 : 43
REMARK 3 SOLVENT ATOMS : 402
REMARK 3
REMARK 3 B VALUES.
REMARK 3 FROM WILSON PLOT (A**2) : NULL
REMARK 3 MEAN B VALUE (OVERALL, A**2) : 22.10
REMARK 3 OVERALL ANISOTROPIC B VALUE.
REMARK 3 B11 (A**2) : 0.86000
REMARK 3 B22 (A**2) : 0.37000
REMARK 3 B33 (A**2) : -1.24000
REMARK 3 B12 (A**2) : 0.00000
REMARK 3 B13 (A**2) : 0.00000
REMARK 3 B23 (A**2) : 0.00000
REMARK 3
REMARK 3 ESTIMATED OVERALL COORDINATE ERROR.
REMARK 3 ESU BASED ON R VALUE (A): 0.112
REMARK 3 ESU BASED ON FREE R VALUE (A): 0.104
REMARK 3 ESU BASED ON MAXIMUM LIKELIHOOD (A): 0.064
REMARK 3 ESU FOR B VALUES BASED ON MAXIMUM LIKELIHOOD (A**2): 1.932
REMARK 3
REMARK 3 CORRELATION COEFFICIENTS.
REMARK 3 CORRELATION COEFFICIENT FO-FC : 0.966
REMARK 3 CORRELATION COEFFICIENT FO-FC FREE : 0.955
REMARK 3
REMARK 3 RMS DEVIATIONS FROM IDEAL VALUES COUNT RMS WEIGHT
REMARK 3 BOND LENGTHS REFINED ATOMS (A): 3149 ; 0.010 ; 0.022
REMARK 3 BOND LENGTHS OTHERS (A): 2068 ; 0.001 ; 0.020
REMARK 3 BOND ANGLES REFINED ATOMS (DEGREES): 4303 ; 1.297 ; 1.961
REMARK 3 BOND ANGLES OTHERS (DEGREES): 5038 ; 0.834 ; 3.000
REMARK 3 TORSION ANGLES, PERIOD 1 (DEGREES): 392 ; 6.341 ; 5.000
REMARK 3 TORSION ANGLES, PERIOD 2 (DEGREES): 141 ;32.683 ;23.830
REMARK 3 TORSION ANGLES, PERIOD 3 (DEGREES): 497 ;11.461 ;15.000
REMARK 3 TORSION ANGLES, PERIOD 4 (DEGREES): 18 ;15.329 ;15.000
REMARK 3 CHIRAL-CENTER RESTRAINTS (A**3): 463 ; 0.077 ; 0.200
REMARK 3 GENERAL PLANES REFINED ATOMS (A): 3605 ; 0.005 ; 0.021
REMARK 3 GENERAL PLANES OTHERS (A): 660 ; 0.001 ; 0.020
REMARK 3 NON-BONDED CONTACTS REFINED ATOMS (A): NULL ; NULL ; NULL
REMARK 3 NON-BONDED CONTACTS OTHERS (A): NULL ; NULL ; NULL
REMARK 3 NON-BONDED TORSION REFINED ATOMS (A): NULL ; NULL ; NULL
REMARK 3 NON-BONDED TORSION OTHERS (A): NULL ; NULL ; NULL
REMARK 3 H-BOND (X...Y) REFINED ATOMS (A): NULL ; NULL ; NULL
REMARK 3 H-BOND (X...Y) OTHERS (A): NULL ; NULL ; NULL
REMARK 3 POTENTIAL METAL-ION REFINED ATOMS (A): NULL ; NULL ; NULL
REMARK 3 POTENTIAL METAL-ION OTHERS (A): NULL ; NULL ; NULL
REMARK 3 SYMMETRY VDW REFINED ATOMS (A): NULL ; NULL ; NULL
REMARK 3 SYMMETRY VDW OTHERS (A): NULL ; NULL ; NULL
REMARK 3 SYMMETRY H-BOND REFINED ATOMS (A): NULL ; NULL ; NULL
REMARK 3 SYMMETRY H-BOND OTHERS (A): NULL ; NULL ; NULL
REMARK 3 SYMMETRY METAL-ION REFINED ATOMS (A): NULL ; NULL ; NULL
REMARK 3 SYMMETRY METAL-ION OTHERS (A): NULL ; NULL ; NULL
REMARK 3
REMARK 3 ISOTROPIC THERMAL FACTOR RESTRAINTS. COUNT RMS WEIGHT
REMARK 3 MAIN-CHAIN BOND REFINED ATOMS (A**2): 1912 ; 0.742 ; 1.500
REMARK 3 MAIN-CHAIN BOND OTHER ATOMS (A**2): 778 ; 0.153 ; 1.500
REMARK 3 MAIN-CHAIN ANGLE REFINED ATOMS (A**2): 3117 ; 1.393 ; 2.000
REMARK 3 MAIN-CHAIN ANGLE OTHER ATOMS (A**2): NULL ; NULL ; NULL
REMARK 3 SIDE-CHAIN BOND REFINED ATOMS (A**2): 1237 ; 2.052 ; 3.000
REMARK 3 SIDE-CHAIN BOND OTHER ATOMS (A**2): NULL ; NULL ; NULL
REMARK 3 SIDE-CHAIN ANGLE REFINED ATOMS (A**2): 1186 ; 3.492 ; 4.500
REMARK 3 SIDE-CHAIN ANGLE OTHER ATOMS (A**2): NULL ; NULL ; NULL
REMARK 3 LONG RANGE B REFINED ATOMS (A**2): NULL ; NULL ; NULL
REMARK 3 LONG RANGE B OTHER ATOMS (A**2): NULL ; NULL ; NULL
REMARK 3
REMARK 3 ANISOTROPIC THERMAL FACTOR RESTRAINTS. COUNT RMS WEIGHT
REMARK 3 RIGID-BOND RESTRAINTS (A**2): NULL ; NULL ; NULL
REMARK 3 SPHERICITY; FREE ATOMS (A**2): NULL ; NULL ; NULL
REMARK 3 SPHERICITY; BONDED ATOMS (A**2): NULL ; NULL ; NULL
REMARK 3
REMARK 3 NCS RESTRAINTS STATISTICS
REMARK 3 NUMBER OF DIFFERENT NCS GROUPS : NULL
REMARK 3
REMARK 3 TLS DETAILS
REMARK 3 NUMBER OF TLS GROUPS : NULL
REMARK 3
REMARK 3 BULK SOLVENT MODELLING.
REMARK 3 METHOD USED : BABINET MODEL WITH MASK
REMARK 3 PARAMETERS FOR MASK CALCULATION
REMARK 3 VDW PROBE RADIUS : 1.40
REMARK 3 ION PROBE RADIUS : 0.80
REMARK 3 SHRINKAGE RADIUS : 0.80
REMARK 3
REMARK 3 OTHER REFINEMENT REMARKS: HYDROGENS HAVE BEEN ADDED IN THE RIDING
REMARK 3 POSITIONS.
REMARK 4
REMARK 4 2XFI COMPLIES WITH FORMAT V. 3.30, 13-JUL-11
REMARK 100
REMARK 100 THIS ENTRY HAS BEEN PROCESSED BY PDBE ON 24-MAY-10.
REMARK 100 THE DEPOSITION ID IS D_1290044056.
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 : 40540
REMARK 200 RESOLUTION RANGE HIGH (A) : 1.700
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 (%) : 98.7
REMARK 200 DATA REDUNDANCY : 4.700
REMARK 200 R MERGE (I) : 0.06000
REMARK 200 R SYM (I) : NULL
REMARK 200 <I/SIGMA(I)> FOR THE DATA SET : 23.2000
REMARK 200
REMARK 200 IN THE HIGHEST RESOLUTION SHELL.
REMARK 200 HIGHEST RESOLUTION SHELL, RANGE HIGH (A) : 1.70
REMARK 200 HIGHEST RESOLUTION SHELL, RANGE LOW (A) : 1.73
REMARK 200 COMPLETENESS FOR SHELL (%) : 99.9
REMARK 200 DATA REDUNDANCY IN SHELL : NULL
REMARK 200 R MERGE FOR SHELL (I) : 0.18000
REMARK 200 R SYM FOR SHELL (I) : NULL
REMARK 200 <I/SIGMA(I)> FOR SHELL : 6.800
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 (%): 38.32
REMARK 280 MATTHEWS COEFFICIENT, VM (ANGSTROMS**3/DA): 2.01
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 24.16700
REMARK 290 SMTRY2 2 0.000000 -1.000000 0.000000 0.00000
REMARK 290 SMTRY3 2 0.000000 0.000000 1.000000 52.34750
REMARK 290 SMTRY1 3 -1.000000 0.000000 0.000000 0.00000
REMARK 290 SMTRY2 3 0.000000 1.000000 0.000000 38.47650
REMARK 290 SMTRY3 3 0.000000 0.000000 -1.000000 52.34750
REMARK 290 SMTRY1 4 1.000000 0.000000 0.000000 24.16700
REMARK 290 SMTRY2 4 0.000000 -1.000000 0.000000 38.47650
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 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 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: CLOSE CONTACTS IN SAME ASYMMETRIC UNIT
REMARK 500
REMARK 500 THE FOLLOWING ATOMS ARE IN CLOSE CONTACT.
REMARK 500
REMARK 500 ATM1 RES C SSEQI ATM2 RES C SSEQI DISTANCE
REMARK 500 O HOH A 2352 O HOH A 2357 2.03
REMARK 500 NE2 GLN A 365 O HOH A 2325 2.05
REMARK 500
REMARK 500 REMARK: NULL
REMARK 500
REMARK 500 GEOMETRY AND STEREOCHEMISTRY
REMARK 500 SUBTOPIC: TORSION ANGLES
REMARK 500
REMARK 500 TORSION ANGLES OUTSIDE THE EXPECTED RAMACHANDRAN REGIONS:
REMARK 500 (M=MODEL NUMBER; RES=RESIDUE NAME; C=CHAIN IDENTIFIER;
REMARK 500 SSEQ=SEQUENCE NUMBER; I=INSERTION CODE).
REMARK 500
REMARK 500 STANDARD TABLE:
REMARK 500 FORMAT:(10X,I3,1X,A3,1X,A1,I4,A1,4X,F7.2,3X,F7.2)
REMARK 500
REMARK 500 EXPECTED VALUES: GJ KLEYWEGT AND TA JONES (1996). PHI/PSI-
REMARK 500 CHOLOGY: RAMACHANDRAN REVISITED. STRUCTURE 4, 1395 - 1400
REMARK 500
REMARK 500 M RES CSSEQI PSI PHI
REMARK 500 PHE A 169 -63.87 -100.97
REMARK 500 TRP A 258 -87.72 -142.36
REMARK 500 ASN A 270 49.38 39.33
REMARK 500 GLN A 354 17.41 59.98
REMARK 500 ASP A 372 116.29 -160.65
REMARK 500 ASP A 372 116.18 -160.65
REMARK 500 HIS A 423 153.01 29.50
REMARK 500 ASP A 424 -164.76 -113.88
REMARK 500
REMARK 500 REMARK: NULL
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 XFI A 1448
REMARK 900
REMARK 900 RELATED ENTRIES
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: 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: 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: 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: 2FDP RELATED DB: PDB
REMARK 900 CRYSTAL STRUCTURE OF BETA-SECRETASE COMPLEXED WITH AN AMINO-
REMARK 900 ETHYLENE 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
REMARK 900 RELATED ID: 1YM4 RELATED DB: PDB
REMARK 900 CRYSTAL STRUCTURE OF HUMAN BETA SECRETASE COMPLEXED WITHNVP-AMK640
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
REMARK 900 RELATED ID: 1SGZ RELATED DB: PDB
REMARK 900 CRYSTAL STRUCTURE OF UNBOUND BETA-SECRETASE CATALYTICDOMAIN.
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: 2VA7 RELATED DB: PDB
REMARK 900 X-RAY CRYSTAL STRUCTURE OF BETA SECRETASE COMPLEXED WITH COMPOUND 27
REMARK 900 RELATED ID: 2WJO RELATED DB: PDB
REMARK 900 HUMAN BACE (BETA SECRETASE) IN COMPLEX WITH CYCLOHEXANECARBOXYLIC
REMARK 900 ACID (2-(2-AM INO-6 -PHENOXY-4H-QUINAZOLIN-3-YL)-2 -CYCLOHEXYL -
REMARK 900 ETHYL)-AMIDE
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: 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: 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: 2WF0 RELATED DB: PDB
REMARK 900 HUMAN BACE-1 IN COMPLEX WITH 4-ETHYL-N -((1S,2R)-2-HYDROXY-1-
REMARK 900 (PHENYLMETHYL)-3-((( 3-(TRIFLUOROMETHYL)PHENYL)METHYL)AMINO)PROPYL )
REMARK 900 -8-(2-OXO-1-PYRROLIDINYL)-6- QUINOLINECARBOXAMIDE
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: 1TQF RELATED DB: PDB
REMARK 900 CRYSTAL STRUCTURE OF HUMAN BETA SECRETASE COMPLEXED WITH L-124,671
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: 2VA6 RELATED DB: PDB
REMARK 900 X-RAY CRYSTAL STRUCTURE OF BETA SECRETASE COMPLEXED WITH COMPOUND 24
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: 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: 2VA5 RELATED DB: PDB
REMARK 900 X-RAY CRYSTAL STRUCTURE OF BETA SECRETASE COMPLEXED WITH COMPOUND 8C
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: 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: 1UJJ RELATED DB: PDB
REMARK 900 VHS DOMAIN OF HUMAN GGA1 COMPLEXED WITH C -TERMINAL PEPTIDEFROM BACE
REMARK 900 RELATED ID: 2XFJ 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: 2XFK 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-((METHYLSULFONYL)( PHENYL)
REMARK 900 AMINO)BENZAMIDE
DBREF 2XFI A 61 452 UNP P56817 BACE1_HUMAN 61 452
SEQADV 2XFI GLN A 153 UNP P56817 ASN 153 ENGINEERED MUTATION
SEQADV 2XFI GLN A 172 UNP P56817 ASN 172 ENGINEERED MUTATION
SEQADV 2XFI GLN A 223 UNP P56817 ASN 223 ENGINEERED MUTATION
SEQADV 2XFI 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 XFI A1448 43
HETNAM XFI N-((1S,2R)-3-(((1S)-2-(CYCLOHEXYLAMINO)-1-METHYL-2-
HETNAM 2 XFI OXOETHYL)AMINO)-2-HYDROXY-1-( PHENYLMETHYL)PROPYL)-3-
HETNAM 3 XFI ((METHYLSULFONYL)(PHENYL)AMINO) BENZAMIDE
FORMUL 2 XFI C33 H42 N4 O5 S
FORMUL 3 HOH *402(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 2 ARG A 122 PRO A 131 0
SHEET 2 AB 2 LYS A 136 SER A 147 -1 O TRP A 137 N VAL A 130
SHEET 1 AC 5 GLU A 261 VAL A 262 0
SHEET 2 AC 5 SER A 286 VAL A 288 -1 O SER A 286 N VAL A 262
SHEET 3 AC 5 THR A 392 MET A 394 1 O THR A 392 N ILE A 287
SHEET 4 AC 5 LEU A 295 PRO A 298 -1 O ARG A 296 N VAL A 393
SHEET 5 AC 5 ILE A 385 SER A 388 1 O SER A 386 N LEU A 297
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 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 2.05
SSBOND 2 CYS A 278 CYS A 443 1555 1555 2.06
SSBOND 3 CYS A 330 CYS A 380 1555 1555 2.08
CISPEP 1 SER A 83 PRO A 84 0 -2.04
CISPEP 2 SER A 83 PRO A 84 0 -3.63
CISPEP 3 ARG A 189 PRO A 190 0 4.29
CISPEP 4 TYR A 283 ASP A 284 0 0.84
CISPEP 5 GLY A 433 PRO A 434 0 -1.38
SITE 1 AC1 20 LEU A 91 ASP A 93 GLY A 95 SER A 96
SITE 2 AC1 20 VAL A 130 PRO A 131 TYR A 132 THR A 133
SITE 3 AC1 20 GLN A 134 PHE A 169 ILE A 179 TYR A 259
SITE 4 AC1 20 ASP A 289 GLY A 291 THR A 292 THR A 293
SITE 5 AC1 20 ASN A 294 ARG A 296 SER A 386 HOH A2402
CRYST1 48.334 76.953 104.695 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 0.012995 0.000000 0.00000
SCALE3 0.000000 0.000000 0.009552 0.00000
(ATOM LINES ARE NOT SHOWN.)
END