HEADER HYDROLASE/HYDROLASE INHIBITOR 01-FEB-13 4J1H
TITLE CRYSTAL STRUCTURE OF BACE-1 IN COMPLEX WITH 5-CYANO-PYRIDINE-2-
TITLE 2 CARBOXYLIC ACID [3-((4S,6R)-2-AMINO-4-METHYL-6-TRIFLUOROMETHYL-5,6-
TITLE 3 DIHYDRO-4H-[1,3]OXAZIN-4-YL)-4-FLUORO-PHENYL]-AMIDE
COMPND MOL_ID: 1;
COMPND 2 MOLECULE: BETA-SECRETASE 1;
COMPND 3 CHAIN: A;
COMPND 4 SYNONYM: ASPARTYL PROTEASE 2, ASP2, ASP 2, BETA-SITE AMYLOID
COMPND 5 PRECURSOR PROTEIN CLEAVING ENZYME 1, BETA-SITE APP CLEAVING ENZYME 1,
COMPND 6 MEMAPSIN-2, MEMBRANE-ASSOCIATED ASPARTIC PROTEASE 2;
COMPND 7 EC: 3.4.23.46;
COMPND 8 ENGINEERED: YES;
COMPND 9 MUTATION: YES
SOURCE MOL_ID: 1;
SOURCE 2 ORGANISM_SCIENTIFIC: HOMO SAPIENS;
SOURCE 3 ORGANISM_COMMON: HUMAN;
SOURCE 4 ORGANISM_TAXID: 9606;
SOURCE 5 GENE: BACE1, BACE, KIAA1149;
SOURCE 6 EXPRESSION_SYSTEM: ESCHERICHIA COLI;
SOURCE 7 EXPRESSION_SYSTEM_TAXID: 562
KEYWDS PROTEASE INHIBITOR, HYDROLASE-HYDROLASE INHIBITOR COMPLEX
EXPDTA X-RAY DIFFRACTION
AUTHOR A.KUGLSTATTER,M.STIHLE
REVDAT 3 15-NOV-17 4J1H 1 REMARK
REVDAT 2 19-JUN-13 4J1H 1 JRNL
REVDAT 1 01-MAY-13 4J1H 0
JRNL AUTH H.HILPERT,W.GUBA,T.J.WOLTERING,W.WOSTL,E.PINARD,H.MAUSER,
JRNL AUTH 2 A.V.MAYWEG,M.ROGERS-EVANS,R.HUMM,D.KRUMMENACHER,T.MUSER,
JRNL AUTH 3 C.SCHNIDER,H.JACOBSEN,L.OZMEN,A.BERGADANO,D.W.BANNER,
JRNL AUTH 4 R.HOCHSTRASSER,A.KUGLSTATTER,P.DAVID-PIERSON,H.FISCHER,
JRNL AUTH 5 A.POLARA,R.NARQUIZIAN
JRNL TITL BETA-SECRETASE (BACE1) INHIBITORS WITH HIGH IN VIVO EFFICACY
JRNL TITL 2 SUITABLE FOR CLINICAL EVALUATION IN ALZHEIMER S DISEASE
JRNL REF J.MED.CHEM. V. 56 3980 2013
JRNL REFN ISSN 0022-2623
JRNL PMID 23590342
JRNL DOI 10.1021/JM400225M
REMARK 2
REMARK 2 RESOLUTION. 2.20 ANGSTROMS.
REMARK 3
REMARK 3 REFINEMENT.
REMARK 3 PROGRAM : REFMAC
REMARK 3 AUTHORS : MURSHUDOV,VAGIN,DODSON
REMARK 3
REMARK 3 REFINEMENT TARGET : MAXIMUM LIKELIHOOD
REMARK 3
REMARK 3 DATA USED IN REFINEMENT.
REMARK 3 RESOLUTION RANGE HIGH (ANGSTROMS) : 2.20
REMARK 3 RESOLUTION RANGE LOW (ANGSTROMS) : 47.56
REMARK 3 DATA CUTOFF (SIGMA(F)) : NULL
REMARK 3 COMPLETENESS FOR RANGE (%) : 100.0
REMARK 3 NUMBER OF REFLECTIONS : 26048
REMARK 3
REMARK 3 FIT TO DATA USED IN REFINEMENT.
REMARK 3 CROSS-VALIDATION METHOD : THROUGHOUT
REMARK 3 FREE R VALUE TEST SET SELECTION : RANDOM
REMARK 3 R VALUE (WORKING + TEST SET) : 0.188
REMARK 3 R VALUE (WORKING SET) : 0.186
REMARK 3 FREE R VALUE : 0.236
REMARK 3 FREE R VALUE TEST SET SIZE (%) : 5.000
REMARK 3 FREE R VALUE TEST SET COUNT : 1375
REMARK 3
REMARK 3 FIT IN THE HIGHEST RESOLUTION BIN.
REMARK 3 TOTAL NUMBER OF BINS USED : 20
REMARK 3 BIN RESOLUTION RANGE HIGH (A) : 2.20
REMARK 3 BIN RESOLUTION RANGE LOW (A) : 2.26
REMARK 3 REFLECTION IN BIN (WORKING SET) : 1890
REMARK 3 BIN COMPLETENESS (WORKING+TEST) (%) : 100.0
REMARK 3 BIN R VALUE (WORKING SET) : 0.3260
REMARK 3 BIN FREE R VALUE SET COUNT : 84
REMARK 3 BIN FREE R VALUE : 0.3220
REMARK 3
REMARK 3 NUMBER OF NON-HYDROGEN ATOMS USED IN REFINEMENT.
REMARK 3 PROTEIN ATOMS : 2916
REMARK 3 NUCLEIC ACID ATOMS : 0
REMARK 3 HETEROGEN ATOMS : 36
REMARK 3 SOLVENT ATOMS : 128
REMARK 3
REMARK 3 B VALUES.
REMARK 3 FROM WILSON PLOT (A**2) : 45.30
REMARK 3 MEAN B VALUE (OVERALL, A**2) : 48.51
REMARK 3 OVERALL ANISOTROPIC B VALUE.
REMARK 3 B11 (A**2) : -0.71000
REMARK 3 B22 (A**2) : -0.71000
REMARK 3 B33 (A**2) : 1.07000
REMARK 3 B12 (A**2) : -0.36000
REMARK 3 B13 (A**2) : 0.00000
REMARK 3 B23 (A**2) : 0.00000
REMARK 3
REMARK 3 ESTIMATED OVERALL COORDINATE ERROR.
REMARK 3 ESU BASED ON R VALUE (A): 0.197
REMARK 3 ESU BASED ON FREE R VALUE (A): 0.182
REMARK 3 ESU BASED ON MAXIMUM LIKELIHOOD (A): 0.122
REMARK 3 ESU FOR B VALUES BASED ON MAXIMUM LIKELIHOOD (A**2): 11.184
REMARK 3
REMARK 3 CORRELATION COEFFICIENTS.
REMARK 3 CORRELATION COEFFICIENT FO-FC : 0.959
REMARK 3 CORRELATION COEFFICIENT FO-FC FREE : 0.937
REMARK 3
REMARK 3 RMS DEVIATIONS FROM IDEAL VALUES COUNT RMS WEIGHT
REMARK 3 BOND LENGTHS REFINED ATOMS (A): 3027 ; 0.018 ; 0.019
REMARK 3 BOND LENGTHS OTHERS (A): NULL ; NULL ; NULL
REMARK 3 BOND ANGLES REFINED ATOMS (DEGREES): 4114 ; 1.984 ; 1.957
REMARK 3 BOND ANGLES OTHERS (DEGREES): NULL ; NULL ; NULL
REMARK 3 TORSION ANGLES, PERIOD 1 (DEGREES): 366 ; 7.411 ; 5.000
REMARK 3 TORSION ANGLES, PERIOD 2 (DEGREES): 138 ;31.400 ;23.623
REMARK 3 TORSION ANGLES, PERIOD 3 (DEGREES): 476 ;16.704 ;15.000
REMARK 3 TORSION ANGLES, PERIOD 4 (DEGREES): 18 ;20.424 ;15.000
REMARK 3 CHIRAL-CENTER RESTRAINTS (A**3): 444 ; 0.132 ; 0.200
REMARK 3 GENERAL PLANES REFINED ATOMS (A): 2319 ; 0.010 ; 0.021
REMARK 3 GENERAL PLANES OTHERS (A): NULL ; NULL ; NULL
REMARK 3 NON-BONDED CONTACTS REFINED ATOMS (A): NULL ; NULL ; NULL
REMARK 3 NON-BONDED CONTACTS OTHERS (A): NULL ; NULL ; NULL
REMARK 3 NON-BONDED TORSION REFINED ATOMS (A): NULL ; NULL ; NULL
REMARK 3 NON-BONDED TORSION OTHERS (A): NULL ; NULL ; NULL
REMARK 3 H-BOND (X...Y) REFINED ATOMS (A): NULL ; NULL ; NULL
REMARK 3 H-BOND (X...Y) OTHERS (A): NULL ; NULL ; NULL
REMARK 3 POTENTIAL METAL-ION REFINED ATOMS (A): NULL ; NULL ; NULL
REMARK 3 POTENTIAL METAL-ION OTHERS (A): NULL ; NULL ; NULL
REMARK 3 SYMMETRY VDW REFINED ATOMS (A): NULL ; NULL ; NULL
REMARK 3 SYMMETRY VDW OTHERS (A): NULL ; NULL ; NULL
REMARK 3 SYMMETRY H-BOND REFINED ATOMS (A): NULL ; NULL ; NULL
REMARK 3 SYMMETRY H-BOND OTHERS (A): NULL ; NULL ; NULL
REMARK 3 SYMMETRY METAL-ION REFINED ATOMS (A): NULL ; NULL ; NULL
REMARK 3 SYMMETRY METAL-ION OTHERS (A): NULL ; NULL ; NULL
REMARK 3
REMARK 3 ISOTROPIC THERMAL FACTOR RESTRAINTS. COUNT RMS WEIGHT
REMARK 3 MAIN-CHAIN BOND REFINED ATOMS (A**2): NULL ; NULL ; NULL
REMARK 3 MAIN-CHAIN BOND OTHER ATOMS (A**2): NULL ; NULL ; NULL
REMARK 3 MAIN-CHAIN ANGLE REFINED ATOMS (A**2): NULL ; NULL ; NULL
REMARK 3 MAIN-CHAIN ANGLE OTHER ATOMS (A**2): NULL ; NULL ; NULL
REMARK 3 SIDE-CHAIN BOND REFINED ATOMS (A**2): NULL ; NULL ; NULL
REMARK 3 SIDE-CHAIN BOND OTHER ATOMS (A**2): NULL ; NULL ; NULL
REMARK 3 SIDE-CHAIN ANGLE REFINED ATOMS (A**2): NULL ; NULL ; NULL
REMARK 3 SIDE-CHAIN ANGLE OTHER ATOMS (A**2): NULL ; NULL ; NULL
REMARK 3 LONG RANGE B REFINED ATOMS (A**2): NULL ; NULL ; NULL
REMARK 3 LONG RANGE B OTHER ATOMS (A**2): NULL ; NULL ; NULL
REMARK 3
REMARK 3 ANISOTROPIC THERMAL FACTOR RESTRAINTS. COUNT RMS WEIGHT
REMARK 3 RIGID-BOND RESTRAINTS (A**2): NULL ; NULL ; NULL
REMARK 3 SPHERICITY; FREE ATOMS (A**2): NULL ; NULL ; NULL
REMARK 3 SPHERICITY; BONDED ATOMS (A**2): NULL ; NULL ; NULL
REMARK 3
REMARK 3 NCS RESTRAINTS STATISTICS
REMARK 3 NUMBER OF DIFFERENT NCS GROUPS : NULL
REMARK 3
REMARK 3 TLS DETAILS
REMARK 3 NUMBER OF TLS GROUPS : 1
REMARK 3
REMARK 3 TLS GROUP : 1
REMARK 3 NUMBER OF COMPONENTS GROUP : 3
REMARK 3 COMPONENTS C SSSEQI TO C SSSEQI
REMARK 3 RESIDUE RANGE : A 1001 A 1128
REMARK 3 RESIDUE RANGE : A 501 A 504
REMARK 3 RESIDUE RANGE : A 57 A 446
REMARK 3 ORIGIN FOR THE GROUP (A): 12.9919 41.2625 -0.0161
REMARK 3 T TENSOR
REMARK 3 T11: 0.0395 T22: 0.0285
REMARK 3 T33: 0.0410 T12: -0.0213
REMARK 3 T13: 0.0131 T23: -0.0052
REMARK 3 L TENSOR
REMARK 3 L11: 3.2084 L22: 0.9589
REMARK 3 L33: 1.3650 L12: -1.4045
REMARK 3 L13: -1.1282 L23: 0.3726
REMARK 3 S TENSOR
REMARK 3 S11: 0.0130 S12: -0.0125 S13: 0.2659
REMARK 3 S21: 0.0128 S22: 0.0223 S23: -0.1690
REMARK 3 S31: -0.0333 S32: 0.0254 S33: -0.0353
REMARK 3
REMARK 3 BULK SOLVENT MODELLING.
REMARK 3 METHOD USED : MASK
REMARK 3 PARAMETERS FOR MASK CALCULATION
REMARK 3 VDW PROBE RADIUS : 1.20
REMARK 3 ION PROBE RADIUS : 0.80
REMARK 3 SHRINKAGE RADIUS : 0.80
REMARK 3
REMARK 3 OTHER REFINEMENT REMARKS: NULL
REMARK 4
REMARK 4 4J1H COMPLIES WITH FORMAT V. 3.30, 13-JUL-11
REMARK 100
REMARK 100 THIS ENTRY HAS BEEN PROCESSED BY RCSB ON 07-FEB-13.
REMARK 100 THE DEPOSITION ID IS D_1000077476.
REMARK 200
REMARK 200 EXPERIMENTAL DETAILS
REMARK 200 EXPERIMENT TYPE : X-RAY DIFFRACTION
REMARK 200 DATE OF DATA COLLECTION : 30-APR-12
REMARK 200 TEMPERATURE (KELVIN) : 100
REMARK 200 PH : 7.0
REMARK 200 NUMBER OF CRYSTALS USED : 1
REMARK 200
REMARK 200 SYNCHROTRON (Y/N) : Y
REMARK 200 RADIATION SOURCE : SLS
REMARK 200 BEAMLINE : X10SA
REMARK 200 X-RAY GENERATOR MODEL : NULL
REMARK 200 MONOCHROMATIC OR LAUE (M/L) : M
REMARK 200 WAVELENGTH OR RANGE (A) : 1.0000
REMARK 200 MONOCHROMATOR : NULL
REMARK 200 OPTICS : NULL
REMARK 200
REMARK 200 DETECTOR TYPE : PIXEL
REMARK 200 DETECTOR MANUFACTURER : DECTRIS PILATUS 6M
REMARK 200 INTENSITY-INTEGRATION SOFTWARE : XDS
REMARK 200 DATA SCALING SOFTWARE : SCALA
REMARK 200
REMARK 200 NUMBER OF UNIQUE REFLECTIONS : 30618
REMARK 200 RESOLUTION RANGE HIGH (A) : 2.120
REMARK 200 RESOLUTION RANGE LOW (A) : 49.120
REMARK 200 REJECTION CRITERIA (SIGMA(I)) : NULL
REMARK 200
REMARK 200 OVERALL.
REMARK 200 COMPLETENESS FOR RANGE (%) : 100.0
REMARK 200 DATA REDUNDANCY : 19.30
REMARK 200 R MERGE (I) : NULL
REMARK 200 R SYM (I) : 0.15200
REMARK 200 <I/SIGMA(I)> FOR THE DATA SET : 15.6000
REMARK 200
REMARK 200 IN THE HIGHEST RESOLUTION SHELL.
REMARK 200 HIGHEST RESOLUTION SHELL, RANGE HIGH (A) : 2.12
REMARK 200 HIGHEST RESOLUTION SHELL, RANGE LOW (A) : 2.23
REMARK 200 COMPLETENESS FOR SHELL (%) : 100.0
REMARK 200 DATA REDUNDANCY IN SHELL : 19.20
REMARK 200 R MERGE FOR SHELL (I) : NULL
REMARK 200 R SYM FOR SHELL (I) : NULL
REMARK 200 <I/SIGMA(I)> FOR SHELL : 1.400
REMARK 200
REMARK 200 DIFFRACTION PROTOCOL: SINGLE WAVELENGTH
REMARK 200 METHOD USED TO DETERMINE THE STRUCTURE: FOURIER SYNTHESIS
REMARK 200 SOFTWARE USED: REFMAC
REMARK 200 STARTING MODEL: NULL
REMARK 200
REMARK 200 REMARK: NULL
REMARK 280
REMARK 280 CRYSTAL
REMARK 280 SOLVENT CONTENT, VS (%): 56.40
REMARK 280 MATTHEWS COEFFICIENT, VM (ANGSTROMS**3/DA): 2.82
REMARK 280
REMARK 280 CRYSTALLIZATION CONDITIONS: 2.5M SODIUM FORMATE, 100MM HEPES, PH
REMARK 280 7.0, VAPOR DIFFUSION, SITTING DROP, TEMPERATURE 298K
REMARK 290
REMARK 290 CRYSTALLOGRAPHIC SYMMETRY
REMARK 290 SYMMETRY OPERATORS FOR SPACE GROUP: P 61 2 2
REMARK 290
REMARK 290 SYMOP SYMMETRY
REMARK 290 NNNMMM OPERATOR
REMARK 290 1555 X,Y,Z
REMARK 290 2555 -Y,X-Y,Z+1/3
REMARK 290 3555 -X+Y,-X,Z+2/3
REMARK 290 4555 -X,-Y,Z+1/2
REMARK 290 5555 Y,-X+Y,Z+5/6
REMARK 290 6555 X-Y,X,Z+1/6
REMARK 290 7555 Y,X,-Z+1/3
REMARK 290 8555 X-Y,-Y,-Z
REMARK 290 9555 -X,-X+Y,-Z+2/3
REMARK 290 10555 -Y,-X,-Z+5/6
REMARK 290 11555 -X+Y,Y,-Z+1/2
REMARK 290 12555 X,X-Y,-Z+1/6
REMARK 290
REMARK 290 WHERE NNN -> OPERATOR NUMBER
REMARK 290 MMM -> TRANSLATION VECTOR
REMARK 290
REMARK 290 CRYSTALLOGRAPHIC SYMMETRY TRANSFORMATIONS
REMARK 290 THE FOLLOWING TRANSFORMATIONS OPERATE ON THE ATOM/HETATM
REMARK 290 RECORDS IN THIS ENTRY TO PRODUCE CRYSTALLOGRAPHICALLY
REMARK 290 RELATED MOLECULES.
REMARK 290 SMTRY1 1 1.000000 0.000000 0.000000 0.00000
REMARK 290 SMTRY2 1 0.000000 1.000000 0.000000 0.00000
REMARK 290 SMTRY3 1 0.000000 0.000000 1.000000 0.00000
REMARK 290 SMTRY1 2 -0.500000 -0.866025 0.000000 0.00000
REMARK 290 SMTRY2 2 0.866025 -0.500000 0.000000 0.00000
REMARK 290 SMTRY3 2 0.000000 0.000000 1.000000 56.29100
REMARK 290 SMTRY1 3 -0.500000 0.866025 0.000000 0.00000
REMARK 290 SMTRY2 3 -0.866025 -0.500000 0.000000 0.00000
REMARK 290 SMTRY3 3 0.000000 0.000000 1.000000 112.58200
REMARK 290 SMTRY1 4 -1.000000 0.000000 0.000000 0.00000
REMARK 290 SMTRY2 4 0.000000 -1.000000 0.000000 0.00000
REMARK 290 SMTRY3 4 0.000000 0.000000 1.000000 84.43650
REMARK 290 SMTRY1 5 0.500000 0.866025 0.000000 0.00000
REMARK 290 SMTRY2 5 -0.866025 0.500000 0.000000 0.00000
REMARK 290 SMTRY3 5 0.000000 0.000000 1.000000 140.72750
REMARK 290 SMTRY1 6 0.500000 -0.866025 0.000000 0.00000
REMARK 290 SMTRY2 6 0.866025 0.500000 0.000000 0.00000
REMARK 290 SMTRY3 6 0.000000 0.000000 1.000000 28.14550
REMARK 290 SMTRY1 7 -0.500000 0.866025 0.000000 0.00000
REMARK 290 SMTRY2 7 0.866025 0.500000 0.000000 0.00000
REMARK 290 SMTRY3 7 0.000000 0.000000 -1.000000 56.29100
REMARK 290 SMTRY1 8 1.000000 0.000000 0.000000 0.00000
REMARK 290 SMTRY2 8 0.000000 -1.000000 0.000000 0.00000
REMARK 290 SMTRY3 8 0.000000 0.000000 -1.000000 0.00000
REMARK 290 SMTRY1 9 -0.500000 -0.866025 0.000000 0.00000
REMARK 290 SMTRY2 9 -0.866025 0.500000 0.000000 0.00000
REMARK 290 SMTRY3 9 0.000000 0.000000 -1.000000 112.58200
REMARK 290 SMTRY1 10 0.500000 -0.866025 0.000000 0.00000
REMARK 290 SMTRY2 10 -0.866025 -0.500000 0.000000 0.00000
REMARK 290 SMTRY3 10 0.000000 0.000000 -1.000000 140.72750
REMARK 290 SMTRY1 11 -1.000000 0.000000 0.000000 0.00000
REMARK 290 SMTRY2 11 0.000000 1.000000 0.000000 0.00000
REMARK 290 SMTRY3 11 0.000000 0.000000 -1.000000 84.43650
REMARK 290 SMTRY1 12 0.500000 0.866025 0.000000 0.00000
REMARK 290 SMTRY2 12 0.866025 -0.500000 0.000000 0.00000
REMARK 290 SMTRY3 12 0.000000 0.000000 -1.000000 28.14550
REMARK 290
REMARK 290 REMARK: NULL
REMARK 300
REMARK 300 BIOMOLECULE: 1
REMARK 300 SEE REMARK 350 FOR THE AUTHOR PROVIDED AND/OR PROGRAM
REMARK 300 GENERATED ASSEMBLY INFORMATION FOR THE STRUCTURE IN
REMARK 300 THIS ENTRY. THE REMARK MAY ALSO PROVIDE INFORMATION ON
REMARK 300 BURIED SURFACE AREA.
REMARK 350
REMARK 350 COORDINATES FOR A COMPLETE MULTIMER REPRESENTING THE KNOWN
REMARK 350 BIOLOGICALLY SIGNIFICANT OLIGOMERIZATION STATE OF THE
REMARK 350 MOLECULE CAN BE GENERATED BY APPLYING BIOMT TRANSFORMATIONS
REMARK 350 GIVEN BELOW. BOTH NON-CRYSTALLOGRAPHIC AND
REMARK 350 CRYSTALLOGRAPHIC OPERATIONS ARE GIVEN.
REMARK 350
REMARK 350 BIOMOLECULE: 1
REMARK 350 AUTHOR DETERMINED BIOLOGICAL UNIT: MONOMERIC
REMARK 350 SOFTWARE DETERMINED QUATERNARY STRUCTURE: MONOMERIC
REMARK 350 SOFTWARE USED: PISA
REMARK 350 APPLY THE FOLLOWING TO CHAINS: A
REMARK 350 BIOMT1 1 1.000000 0.000000 0.000000 0.00000
REMARK 350 BIOMT2 1 0.000000 1.000000 0.000000 0.00000
REMARK 350 BIOMT3 1 0.000000 0.000000 1.000000 0.00000
REMARK 465
REMARK 465 MISSING RESIDUES
REMARK 465 THE FOLLOWING RESIDUES WERE NOT LOCATED IN THE
REMARK 465 EXPERIMENT. (M=MODEL NUMBER; RES=RESIDUE NAME; C=CHAIN
REMARK 465 IDENTIFIER; SSSEQ=SEQUENCE NUMBER; I=INSERTION CODE.)
REMARK 465
REMARK 465 M RES C SSSEQI
REMARK 465 GLU A 46
REMARK 465 THR A 47
REMARK 465 ASP A 48
REMARK 465 GLU A 49
REMARK 465 GLU A 50
REMARK 465 PRO A 51
REMARK 465 GLU A 52
REMARK 465 GLU A 53
REMARK 465 PRO A 54
REMARK 465 GLY A 55
REMARK 465 ARG A 56
REMARK 465 ALA A 218
REMARK 465 GLY A 219
REMARK 465 PHE A 220
REMARK 465 PRO A 221
REMARK 465 LEU A 222
REMARK 465 ASN A 223
REMARK 465 GLN A 224
REMARK 465 SER A 225
REMARK 465 GLU A 226
REMARK 465 VAL A 227
REMARK 465 LEU A 228
REMARK 465 ALA A 229
REMARK 465 GLY A 334
REMARK 465 THR A 335
REMARK 465 THR A 336
REMARK 465 ALA A 374
REMARK 465 THR A 375
REMARK 465 SER A 376
REMARK 465 GLN A 377
REMARK 465 ASP A 378
REMARK 465 ILE A 447
REMARK 465 PRO A 448
REMARK 465 GLN A 449
REMARK 465 THR A 450
REMARK 465 ASP A 451
REMARK 465 GLU A 452
REMARK 465 SER A 453
REMARK 465 THR A 454
REMARK 470
REMARK 470 MISSING ATOM
REMARK 470 THE FOLLOWING RESIDUES HAVE MISSING ATOMS (M=MODEL NUMBER;
REMARK 470 RES=RESIDUE NAME; C=CHAIN IDENTIFIER; SSEQ=SEQUENCE NUMBER;
REMARK 470 I=INSERTION CODE):
REMARK 470 M RES CSSEQI ATOMS
REMARK 470 ASP A 372 CG OD1 OD2
REMARK 500
REMARK 500 GEOMETRY AND STEREOCHEMISTRY
REMARK 500 SUBTOPIC: COVALENT BOND ANGLES
REMARK 500
REMARK 500 THE STEREOCHEMICAL PARAMETERS OF THE FOLLOWING RESIDUES
REMARK 500 HAVE VALUES WHICH DEVIATE FROM EXPECTED VALUES BY MORE
REMARK 500 THAN 6*RMSD (M=MODEL NUMBER; RES=RESIDUE NAME; C=CHAIN
REMARK 500 IDENTIFIER; SSEQ=SEQUENCE NUMBER; I=INSERTION CODE).
REMARK 500
REMARK 500 STANDARD TABLE:
REMARK 500 FORMAT: (10X,I3,1X,A3,1X,A1,I4,A1,3(1X,A4,2X),12X,F5.1)
REMARK 500
REMARK 500 EXPECTED VALUES PROTEIN: ENGH AND HUBER, 1999
REMARK 500 EXPECTED VALUES NUCLEIC ACID: CLOWNEY ET AL 1996
REMARK 500
REMARK 500 M RES CSSEQI ATM1 ATM2 ATM3
REMARK 500 ARG A 115 NE - CZ - NH1 ANGL. DEV. = -3.4 DEGREES
REMARK 500 ASP A 199 CB - CG - OD2 ANGL. DEV. = 5.8 DEGREES
REMARK 500 ARG A 410 NE - CZ - NH2 ANGL. DEV. = -3.6 DEGREES
REMARK 500
REMARK 500 REMARK: NULL
REMARK 500
REMARK 500 GEOMETRY AND STEREOCHEMISTRY
REMARK 500 SUBTOPIC: TORSION ANGLES
REMARK 500
REMARK 500 TORSION ANGLES OUTSIDE THE EXPECTED RAMACHANDRAN REGIONS:
REMARK 500 (M=MODEL NUMBER; RES=RESIDUE NAME; C=CHAIN IDENTIFIER;
REMARK 500 SSEQ=SEQUENCE NUMBER; I=INSERTION CODE).
REMARK 500
REMARK 500 STANDARD TABLE:
REMARK 500 FORMAT:(10X,I3,1X,A3,1X,A1,I4,A1,4X,F7.2,3X,F7.2)
REMARK 500
REMARK 500 EXPECTED VALUES: GJ KLEYWEGT AND TA JONES (1996). PHI/PSI-
REMARK 500 CHOLOGY: RAMACHANDRAN REVISITED. STRUCTURE 4, 1395 - 1400
REMARK 500
REMARK 500 M RES CSSEQI PSI PHI
REMARK 500 HIS A 150 46.61 -102.54
REMARK 500 TRP A 258 -89.15 -135.81
REMARK 500 SER A 314 21.11 -65.45
REMARK 500 ALA A 429 150.33 -46.99
REMARK 500
REMARK 500 REMARK: NULL
REMARK 620
REMARK 620 METAL COORDINATION
REMARK 620 (M=MODEL NUMBER; RES=RESIDUE NAME; C=CHAIN IDENTIFIER;
REMARK 620 SSEQ=SEQUENCE NUMBER; I=INSERTION CODE):
REMARK 620
REMARK 620 COORDINATION ANGLES FOR: M RES CSSEQI METAL
REMARK 620 NA A 502 NA
REMARK 620 N RES CSSEQI ATOM
REMARK 620 1 VAL A 202 O
REMARK 620 2 HOH A1104 O 92.1
REMARK 620 3 THR A 205 O 89.2 163.9
REMARK 620 N 1 2
REMARK 620
REMARK 620 COORDINATION ANGLES FOR: M RES CSSEQI METAL
REMARK 620 NA A 501 NA
REMARK 620 N RES CSSEQI ATOM
REMARK 620 1 HIS A 242 O
REMARK 620 2 TYR A 245 O 75.8
REMARK 620 3 HOH A1064 O 78.7 70.4
REMARK 620 N 1 2
REMARK 800
REMARK 800 SITE
REMARK 800 SITE_IDENTIFIER: AC1
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: BINDING SITE FOR RESIDUE NA A 501
REMARK 800
REMARK 800 SITE_IDENTIFIER: AC2
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: BINDING SITE FOR RESIDUE NA A 502
REMARK 800
REMARK 800 SITE_IDENTIFIER: AC3
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: BINDING SITE FOR RESIDUE DMS A 503
REMARK 800
REMARK 800 SITE_IDENTIFIER: AC4
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: BINDING SITE FOR RESIDUE 1HJ A 504
REMARK 900
REMARK 900 RELATED ENTRIES
REMARK 900 RELATED ID: 4J0P RELATED DB: PDB
REMARK 900 RELATED ID: 4J0T RELATED DB: PDB
REMARK 900 RELATED ID: 4J0V RELATED DB: PDB
REMARK 900 RELATED ID: 4J0Y RELATED DB: PDB
REMARK 900 RELATED ID: 4J0Z RELATED DB: PDB
REMARK 900 RELATED ID: 4J17 RELATED DB: PDB
REMARK 900 RELATED ID: 4J1C RELATED DB: PDB
REMARK 900 RELATED ID: 4J1E RELATED DB: PDB
REMARK 900 RELATED ID: 4J1F RELATED DB: PDB
REMARK 900 RELATED ID: 4J1I RELATED DB: PDB
REMARK 900 RELATED ID: 4J1K RELATED DB: PDB
DBREF 4J1H A 46 454 UNP P56817 BACE1_HUMAN 46 454
SEQADV 4J1H ALA A 307 UNP P56817 LYS 307 ENGINEERED MUTATION
SEQRES 1 A 409 GLU THR ASP GLU GLU PRO GLU GLU PRO GLY ARG ARG GLY
SEQRES 2 A 409 SER PHE VAL GLU MET VAL ASP ASN LEU ARG GLY LYS SER
SEQRES 3 A 409 GLY GLN GLY TYR TYR VAL GLU MET THR VAL GLY SER PRO
SEQRES 4 A 409 PRO GLN THR LEU ASN ILE LEU VAL ASP THR GLY SER SER
SEQRES 5 A 409 ASN PHE ALA VAL GLY ALA ALA PRO HIS PRO PHE LEU HIS
SEQRES 6 A 409 ARG TYR TYR GLN ARG GLN LEU SER SER THR TYR ARG ASP
SEQRES 7 A 409 LEU ARG LYS GLY VAL TYR VAL PRO TYR THR GLN GLY LYS
SEQRES 8 A 409 TRP GLU GLY GLU LEU GLY THR ASP LEU VAL SER ILE PRO
SEQRES 9 A 409 HIS GLY PRO ASN VAL THR VAL ARG ALA ASN ILE ALA ALA
SEQRES 10 A 409 ILE THR GLU SER ASP LYS PHE PHE ILE ASN GLY SER ASN
SEQRES 11 A 409 TRP GLU GLY ILE LEU GLY LEU ALA TYR ALA GLU ILE ALA
SEQRES 12 A 409 ARG PRO ASP ASP SER LEU GLU PRO PHE PHE ASP SER LEU
SEQRES 13 A 409 VAL LYS GLN THR HIS VAL PRO ASN LEU PHE SER LEU GLN
SEQRES 14 A 409 LEU CYS GLY ALA GLY PHE PRO LEU ASN GLN SER GLU VAL
SEQRES 15 A 409 LEU ALA SER VAL GLY GLY SER MET ILE ILE GLY GLY ILE
SEQRES 16 A 409 ASP HIS SER LEU TYR THR GLY SER LEU TRP TYR THR PRO
SEQRES 17 A 409 ILE ARG ARG GLU TRP TYR TYR GLU VAL ILE ILE VAL ARG
SEQRES 18 A 409 VAL GLU ILE ASN GLY GLN ASP LEU LYS MET ASP CYS LYS
SEQRES 19 A 409 GLU TYR ASN TYR ASP LYS SER ILE VAL ASP SER GLY THR
SEQRES 20 A 409 THR ASN LEU ARG LEU PRO LYS LYS VAL PHE GLU ALA ALA
SEQRES 21 A 409 VAL ALA SER ILE LYS ALA ALA SER SER THR GLU LYS PHE
SEQRES 22 A 409 PRO ASP GLY PHE TRP LEU GLY GLU GLN LEU VAL CYS TRP
SEQRES 23 A 409 GLN ALA GLY THR THR PRO TRP ASN ILE PHE PRO VAL ILE
SEQRES 24 A 409 SER LEU TYR LEU MET GLY GLU VAL THR ASN GLN SER PHE
SEQRES 25 A 409 ARG ILE THR ILE LEU PRO GLN GLN TYR LEU ARG PRO VAL
SEQRES 26 A 409 GLU ASP VAL ALA THR SER GLN ASP ASP CYS TYR LYS PHE
SEQRES 27 A 409 ALA ILE SER GLN SER SER THR GLY THR VAL MET GLY ALA
SEQRES 28 A 409 VAL ILE MET GLU GLY PHE TYR VAL VAL PHE ASP ARG ALA
SEQRES 29 A 409 ARG LYS ARG ILE GLY PHE ALA VAL SER ALA CYS HIS VAL
SEQRES 30 A 409 HIS ASP GLU PHE ARG THR ALA ALA VAL GLU GLY PRO PHE
SEQRES 31 A 409 VAL THR LEU ASP MET GLU ASP CYS GLY TYR ASN ILE PRO
SEQRES 32 A 409 GLN THR ASP GLU SER THR
HET NA A 501 1
HET NA A 502 1
HET DMS A 503 4
HET 1HJ A 504 30
HETNAM NA SODIUM ION
HETNAM DMS DIMETHYL SULFOXIDE
HETNAM 1HJ N-{3-[(4S,6R)-2-AMINO-4-METHYL-6-(TRIFLUOROMETHYL)-5,6-
HETNAM 2 1HJ DIHYDRO-4H-1,3-OXAZIN-4-YL]-4-FLUOROPHENYL}-5-
HETNAM 3 1HJ CYANOPYRIDINE-2-CARBOXAMIDE
FORMUL 2 NA 2(NA 1+)
FORMUL 4 DMS C2 H6 O S
FORMUL 5 1HJ C19 H15 F4 N5 O2
FORMUL 6 HOH *128(H2 O)
HELIX 1 1 GLN A 114 SER A 118 5 5
HELIX 2 2 TYR A 184 ALA A 188 5 5
HELIX 3 3 PRO A 196 THR A 205 1 10
HELIX 4 4 ASP A 241 SER A 243 5 3
HELIX 5 5 ASP A 277 TYR A 283 5 7
HELIX 6 6 LYS A 299 SER A 314 1 16
HELIX 7 7 PRO A 319 LEU A 324 1 6
HELIX 8 8 LEU A 362 TYR A 366 1 5
HELIX 9 9 GLY A 395 GLU A 400 1 6
HELIX 10 10 ARG A 408 ARG A 410 5 3
HELIX 11 11 ASP A 439 GLY A 444 5 6
SHEET 1 A 9 ARG A 122 PRO A 131 0
SHEET 2 A 9 LYS A 136 SER A 147 -1 O TRP A 137 N VAL A 130
SHEET 3 A 9 TYR A 76 VAL A 81 -1 N THR A 80 O SER A 147
SHEET 4 A 9 LEU A 67 GLY A 69 -1 N ARG A 68 O TYR A 76
SHEET 5 A 9 VAL A 231 ILE A 237 -1 O VAL A 231 N GLY A 69
SHEET 6 A 9 PHE A 211 CYS A 216 -1 N GLN A 214 O SER A 234
SHEET 7 A 9 PHE A 402 ASP A 407 -1 O VAL A 404 N LEU A 213
SHEET 8 A 9 ARG A 412 SER A 418 -1 O GLY A 414 N VAL A 405
SHEET 9 A 9 TYR A 245 PRO A 253 -1 N THR A 252 O ILE A 413
SHEET 1 B13 ARG A 122 PRO A 131 0
SHEET 2 B13 LYS A 136 SER A 147 -1 O TRP A 137 N VAL A 130
SHEET 3 B13 THR A 155 ASP A 167 -1 O ALA A 162 N GLU A 140
SHEET 4 B13 PHE A 99 GLY A 102 1 N VAL A 101 O ILE A 163
SHEET 5 B13 GLY A 178 GLY A 181 -1 O ILE A 179 N ALA A 100
SHEET 6 B13 GLN A 86 ASP A 93 1 N LEU A 91 O LEU A 180
SHEET 7 B13 TYR A 76 VAL A 81 -1 N MET A 79 O LEU A 88
SHEET 8 B13 LEU A 67 GLY A 69 -1 N ARG A 68 O TYR A 76
SHEET 9 B13 VAL A 231 ILE A 237 -1 O VAL A 231 N GLY A 69
SHEET 10 B13 PHE A 211 CYS A 216 -1 N GLN A 214 O SER A 234
SHEET 11 B13 PHE A 402 ASP A 407 -1 O VAL A 404 N LEU A 213
SHEET 12 B13 ARG A 412 SER A 418 -1 O GLY A 414 N VAL A 405
SHEET 13 B13 TYR A 245 PRO A 253 -1 N THR A 252 O ILE A 413
SHEET 1 C 5 GLU A 261 VAL A 262 0
SHEET 2 C 5 SER A 286 VAL A 288 -1 O SER A 286 N VAL A 262
SHEET 3 C 5 THR A 392 MET A 394 1 O MET A 394 N ILE A 287
SHEET 4 C 5 LEU A 295 PRO A 298 -1 N ARG A 296 O VAL A 393
SHEET 5 C 5 ILE A 385 SER A 388 1 O SER A 386 N LEU A 297
SHEET 1 D 5 GLN A 272 ASP A 273 0
SHEET 2 D 5 ILE A 264 ILE A 269 -1 N ILE A 269 O GLN A 272
SHEET 3 D 5 ILE A 344 MET A 349 -1 O TYR A 347 N ARG A 266
SHEET 4 D 5 GLN A 355 ILE A 361 -1 O ILE A 359 N LEU A 346
SHEET 5 D 5 ALA A 430 VAL A 436 -1 O GLU A 432 N ARG A 358
SHEET 1 E 3 VAL A 329 CYS A 330 0
SHEET 2 E 3 CYS A 380 PHE A 383 -1 O TYR A 381 N VAL A 329
SHEET 3 E 3 LEU A 367 PRO A 369 -1 N ARG A 368 O LYS A 382
SSBOND 1 CYS A 216 CYS A 420 1555 1555 2.11
SSBOND 2 CYS A 278 CYS A 443 1555 1555 2.10
SSBOND 3 CYS A 330 CYS A 380 1555 1555 2.07
LINK O VAL A 202 NA NA A 502 1555 1555 2.24
LINK NA NA A 502 O HOH A1104 1555 1555 2.40
LINK O THR A 205 NA NA A 502 1555 1555 2.41
LINK O HIS A 242 NA NA A 501 1555 1555 2.45
LINK O TYR A 245 NA NA A 501 1555 1555 2.56
LINK NA NA A 501 O HOH A1064 1555 1555 2.67
CISPEP 1 SER A 83 PRO A 84 0 -7.74
CISPEP 2 ARG A 189 PRO A 190 0 3.35
CISPEP 3 TYR A 283 ASP A 284 0 -0.72
CISPEP 4 GLY A 433 PRO A 434 0 -1.35
SITE 1 AC1 3 HIS A 242 TYR A 245 HOH A1064
SITE 1 AC2 3 VAL A 202 THR A 205 HOH A1104
SITE 1 AC3 2 ARG A 157 GLU A 195
SITE 1 AC4 14 GLY A 72 GLN A 73 GLY A 74 LEU A 91
SITE 2 AC4 14 ASP A 93 TYR A 132 PHE A 169 TRP A 176
SITE 3 AC4 14 ILE A 179 ASP A 289 SER A 290 GLY A 291
SITE 4 AC4 14 THR A 293 ALA A 396
CRYST1 102.685 102.685 168.873 90.00 90.00 120.00 P 61 2 2 12
ORIGX1 1.000000 0.000000 0.000000 0.00000
ORIGX2 0.000000 1.000000 0.000000 0.00000
ORIGX3 0.000000 0.000000 1.000000 0.00000
SCALE1 0.009739 0.005623 0.000000 0.00000
SCALE2 0.000000 0.011245 0.000000 0.00000
SCALE3 0.000000 0.000000 0.005922 0.00000
(ATOM LINES ARE NOT SHOWN.)
END