HEADER HYDROLASE/HYDROLASE INHIBITOR 13-MAY-15 4ZSP
TITLE BACE CRYSTAL STRUCTURE WITH BICYCLIC AMINOTHIAZINE INHIBITOR
COMPND MOL_ID: 1;
COMPND 2 MOLECULE: BETA-SECRETASE 1;
COMPND 3 CHAIN: A, B;
COMPND 4 FRAGMENT: UNP RESIDUES 14-454;
COMPND 5 SYNONYM: ASPARTYL PROTEASE 2,ASP 2,BETA-SITE AMYLOID PRECURSOR
COMPND 6 PROTEIN CLEAVING ENZYME 1,BETA-SITE APP CLEAVING ENZYME 1,MEMAPSIN-2,
COMPND 7 MEMBRANE-ASSOCIATED ASPARTIC PROTEASE 2;
COMPND 8 EC: 3.4.23.46;
COMPND 9 ENGINEERED: 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 ASPARTYL, PROTEASE, BETA-SECRETASE, HYDROLASE-HYDROLASE INHIBITOR
KEYWDS 2 COMPLEX
EXPDTA X-RAY DIFFRACTION
AUTHOR D.E.TIMM
REVDAT 2 17-JUN-15 4ZSP 1 JRNL
REVDAT 1 10-JUN-15 4ZSP 0
JRNL AUTH L.L.WINNEROSKI,M.A.SCHIFFLER,J.A.ERICKSON,P.C.MAY,S.A.MONK,
JRNL AUTH 2 D.E.TIMM,J.E.AUDIA,J.P.BECK,L.N.BOGGS,A.R.BORDERS,R.D.BOYER,
JRNL AUTH 3 R.A.BRIER,K.J.HUDZIAK,V.J.KLIMKOWSKI,P.GARCIA LOSADA,
JRNL AUTH 4 B.M.MATHES,S.L.STOUT,B.M.WATSON,D.J.MERGOTT
JRNL TITL PREPARATION AND BIOLOGICAL EVALUATION OF CONFORMATIONALLY
JRNL TITL 2 CONSTRAINED BACE1 INHIBITORS.
JRNL REF BIOORG.MED.CHEM. V. 23 3260 2015
JRNL REFN ESSN 1464-3391
JRNL PMID 26001341
JRNL DOI 10.1016/J.BMC.2015.04.062
REMARK 2
REMARK 2 RESOLUTION. 1.91 ANGSTROMS.
REMARK 3
REMARK 3 REFINEMENT.
REMARK 3 PROGRAM : REFMAC 5.8.0069
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) : 1.91
REMARK 3 RESOLUTION RANGE LOW (ANGSTROMS) : 75.16
REMARK 3 DATA CUTOFF (SIGMA(F)) : NULL
REMARK 3 COMPLETENESS FOR RANGE (%) : 98.1
REMARK 3 NUMBER OF REFLECTIONS : 79061
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) : 0.189
REMARK 3 R VALUE (WORKING SET) : 0.189
REMARK 3 FREE R VALUE : 0.243
REMARK 3 FREE R VALUE TEST SET SIZE (%) : 1.300
REMARK 3 FREE R VALUE TEST SET COUNT : 1039
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) : 1.91
REMARK 3 BIN RESOLUTION RANGE LOW (A) : 1.96
REMARK 3 REFLECTION IN BIN (WORKING SET) : 5737
REMARK 3 BIN COMPLETENESS (WORKING+TEST) (%) : 97.14
REMARK 3 BIN R VALUE (WORKING SET) : 0.3210
REMARK 3 BIN FREE R VALUE SET COUNT : 62
REMARK 3 BIN FREE R VALUE : 0.3260
REMARK 3
REMARK 3 NUMBER OF NON-HYDROGEN ATOMS USED IN REFINEMENT.
REMARK 3 PROTEIN ATOMS : 6115
REMARK 3 NUCLEIC ACID ATOMS : 0
REMARK 3 HETEROGEN ATOMS : 54
REMARK 3 SOLVENT ATOMS : 838
REMARK 3
REMARK 3 B VALUES.
REMARK 3 FROM WILSON PLOT (A**2) : NULL
REMARK 3 MEAN B VALUE (OVERALL, A**2) : 32.62
REMARK 3 OVERALL ANISOTROPIC B VALUE.
REMARK 3 B11 (A**2) : -3.54000
REMARK 3 B22 (A**2) : 5.53000
REMARK 3 B33 (A**2) : -2.00000
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): 0.136
REMARK 3 ESU BASED ON FREE R VALUE (A): 0.140
REMARK 3 ESU BASED ON MAXIMUM LIKELIHOOD (A): 0.128
REMARK 3 ESU FOR B VALUES BASED ON MAXIMUM LIKELIHOOD (A**2): 4.796
REMARK 3
REMARK 3 CORRELATION COEFFICIENTS.
REMARK 3 CORRELATION COEFFICIENT FO-FC : 0.968
REMARK 3 CORRELATION COEFFICIENT FO-FC FREE : 0.944
REMARK 3
REMARK 3 RMS DEVIATIONS FROM IDEAL VALUES COUNT RMS WEIGHT
REMARK 3 BOND LENGTHS REFINED ATOMS (A): 6371 ; 0.011 ; 0.019
REMARK 3 BOND LENGTHS OTHERS (A): NULL ; NULL ; NULL
REMARK 3 BOND ANGLES REFINED ATOMS (DEGREES): 8675 ; 1.462 ; 1.956
REMARK 3 BOND ANGLES OTHERS (DEGREES): NULL ; NULL ; NULL
REMARK 3 TORSION ANGLES, PERIOD 1 (DEGREES): 789 ; 6.556 ; 5.000
REMARK 3 TORSION ANGLES, PERIOD 2 (DEGREES): 292 ;35.679 ;23.973
REMARK 3 TORSION ANGLES, PERIOD 3 (DEGREES): 1007 ;13.674 ;15.000
REMARK 3 TORSION ANGLES, PERIOD 4 (DEGREES): 35 ;17.608 ;15.000
REMARK 3 CHIRAL-CENTER RESTRAINTS (A**3): 945 ; 0.099 ; 0.200
REMARK 3 GENERAL PLANES REFINED ATOMS (A): 4941 ; 0.007 ; 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): 3126 ; 1.955 ; 2.940
REMARK 3 MAIN-CHAIN BOND OTHER ATOMS (A**2): NULL ; NULL ; NULL
REMARK 3 MAIN-CHAIN ANGLE REFINED ATOMS (A**2): 3907 ; 3.000 ; 4.398
REMARK 3 MAIN-CHAIN ANGLE OTHER ATOMS (A**2): NULL ; NULL ; NULL
REMARK 3 SIDE-CHAIN BOND REFINED ATOMS (A**2): 3245 ; 3.013 ; 3.218
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): 10630 ; 7.039 ;26.550
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 : 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: HYDROGENS HAVE BEEN USED IF PRESENT IN
REMARK 3 THE INPUT
REMARK 4
REMARK 4 4ZSP COMPLIES WITH FORMAT V. 3.30, 13-JUL-11
REMARK 100
REMARK 100 THIS ENTRY HAS BEEN PROCESSED BY RCSB ON 15-MAY-15.
REMARK 100 THE DEPOSITION ID IS D_1000209822.
REMARK 200
REMARK 200 EXPERIMENTAL DETAILS
REMARK 200 EXPERIMENT TYPE : X-RAY DIFFRACTION
REMARK 200 DATE OF DATA COLLECTION : 21-JUL-10
REMARK 200 TEMPERATURE (KELVIN) : 100
REMARK 200 PH : 7.4
REMARK 200 NUMBER OF CRYSTALS USED : NULL
REMARK 200
REMARK 200 SYNCHROTRON (Y/N) : Y
REMARK 200 RADIATION SOURCE : APS
REMARK 200 BEAMLINE : 31-ID
REMARK 200 X-RAY GENERATOR MODEL : NULL
REMARK 200 MONOCHROMATIC OR LAUE (M/L) : M
REMARK 200 WAVELENGTH OR RANGE (A) : 0.97929
REMARK 200 MONOCHROMATOR : NULL
REMARK 200 OPTICS : NULL
REMARK 200
REMARK 200 DETECTOR TYPE : CCD
REMARK 200 DETECTOR MANUFACTURER : ADSC QUANTUM 210R
REMARK 200 INTENSITY-INTEGRATION SOFTWARE : MOSFLM
REMARK 200 DATA SCALING SOFTWARE : SCALA
REMARK 200
REMARK 200 NUMBER OF UNIQUE REFLECTIONS : 92995
REMARK 200 RESOLUTION RANGE HIGH (A) : 1.820
REMARK 200 RESOLUTION RANGE LOW (A) : 91.700
REMARK 200 REJECTION CRITERIA (SIGMA(I)) : NULL
REMARK 200
REMARK 200 OVERALL.
REMARK 200 COMPLETENESS FOR RANGE (%) : 98.2
REMARK 200 DATA REDUNDANCY : 7.500
REMARK 200 R MERGE (I) : NULL
REMARK 200 R SYM (I) : NULL
REMARK 200 <I/SIGMA(I)> FOR THE DATA SET : 8.9000
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: NULL
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 (%): 53.77
REMARK 280 MATTHEWS COEFFICIENT, VM (ANGSTROMS**3/DA): 2.66
REMARK 280
REMARK 280 CRYSTALLIZATION CONDITIONS: PEG8000, SODIUM CACODYLATE, AMMONIUM
REMARK 280 SULFATE, PH 7.4, VAPOR DIFFUSION, HANGING DROP, TEMPERATURE 277K
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 43.32350
REMARK 290 SMTRY2 2 0.000000 -1.000000 0.000000 0.00000
REMARK 290 SMTRY3 2 0.000000 0.000000 1.000000 65.60250
REMARK 290 SMTRY1 3 -1.000000 0.000000 0.000000 0.00000
REMARK 290 SMTRY2 3 0.000000 1.000000 0.000000 45.84450
REMARK 290 SMTRY3 3 0.000000 0.000000 -1.000000 65.60250
REMARK 290 SMTRY1 4 1.000000 0.000000 0.000000 43.32350
REMARK 290 SMTRY2 4 0.000000 -1.000000 0.000000 45.84450
REMARK 290 SMTRY3 4 0.000000 0.000000 -1.000000 0.00000
REMARK 290
REMARK 290 REMARK: NULL
REMARK 300
REMARK 300 BIOMOLECULE: 1, 2
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 350
REMARK 350 BIOMOLECULE: 2
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: B
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 MET A -48
REMARK 465 ALA A -47
REMARK 465 GLY A -46
REMARK 465 VAL A -45
REMARK 465 LEU A -44
REMARK 465 PRO A -43
REMARK 465 ALA A -42
REMARK 465 HIS A -41
REMARK 465 GLY A -40
REMARK 465 THR A -39
REMARK 465 GLN A -38
REMARK 465 HIS A -37
REMARK 465 GLY A -36
REMARK 465 ILE A -35
REMARK 465 ARG A -34
REMARK 465 LEU A -33
REMARK 465 PRO A -32
REMARK 465 LEU A -31
REMARK 465 ARG A -30
REMARK 465 SER A -29
REMARK 465 GLY A -28
REMARK 465 LEU A -27
REMARK 465 GLY A -26
REMARK 465 GLY A -25
REMARK 465 ALA A -24
REMARK 465 PRO A -23
REMARK 465 LEU A -22
REMARK 465 GLY A -21
REMARK 465 LEU A -20
REMARK 465 ARG A -19
REMARK 465 LEU A -18
REMARK 465 PRO A -17
REMARK 465 ARG A -16
REMARK 465 GLU A -15
REMARK 465 THR A -14
REMARK 465 ASP A -13
REMARK 465 GLU A -12
REMARK 465 GLU A -11
REMARK 465 PRO A -10
REMARK 465 GLU A -9
REMARK 465 GLU A -8
REMARK 465 PRO A -7
REMARK 465 GLY A -6
REMARK 465 ARG A -5
REMARK 465 ILE A 386
REMARK 465 PRO A 387
REMARK 465 GLN A 388
REMARK 465 THR A 389
REMARK 465 ASP A 390
REMARK 465 GLU A 391
REMARK 465 SER A 392
REMARK 465 THR A 393
REMARK 465 MET B -48
REMARK 465 ALA B -47
REMARK 465 GLY B -46
REMARK 465 VAL B -45
REMARK 465 LEU B -44
REMARK 465 PRO B -43
REMARK 465 ALA B -42
REMARK 465 HIS B -41
REMARK 465 GLY B -40
REMARK 465 THR B -39
REMARK 465 GLN B -38
REMARK 465 HIS B -37
REMARK 465 GLY B -36
REMARK 465 ILE B -35
REMARK 465 ARG B -34
REMARK 465 LEU B -33
REMARK 465 PRO B -32
REMARK 465 LEU B -31
REMARK 465 ARG B -30
REMARK 465 SER B -29
REMARK 465 GLY B -28
REMARK 465 LEU B -27
REMARK 465 GLY B -26
REMARK 465 GLY B -25
REMARK 465 ALA B -24
REMARK 465 PRO B -23
REMARK 465 LEU B -22
REMARK 465 GLY B -21
REMARK 465 LEU B -20
REMARK 465 ARG B -19
REMARK 465 LEU B -18
REMARK 465 PRO B -17
REMARK 465 ARG B -16
REMARK 465 GLU B -15
REMARK 465 THR B -14
REMARK 465 ASP B -13
REMARK 465 GLU B -12
REMARK 465 GLU B -11
REMARK 465 PRO B -10
REMARK 465 GLU B -9
REMARK 465 GLU B -8
REMARK 465 PRO B -7
REMARK 465 GLY B -6
REMARK 465 ARG B -5
REMARK 465 ARG B -4
REMARK 465 ILE B 386
REMARK 465 PRO B 387
REMARK 465 GLN B 388
REMARK 465 THR B 389
REMARK 465 ASP B 390
REMARK 465 GLU B 391
REMARK 465 SER B 392
REMARK 465 THR B 393
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 538 O HOH A 611 2.14
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 ASN A 114 3.07 81.34
REMARK 500 TRP A 197 -82.32 -133.92
REMARK 500 ALA A 272 125.45 -36.46
REMARK 500 THR A 314 13.54 50.09
REMARK 500 SER A 315 -161.47 -40.91
REMARK 500 HIS B 89 50.74 -96.80
REMARK 500 ASN B 114 -2.70 79.40
REMARK 500 TRP B 197 -85.37 -134.52
REMARK 500 ALA B 323 31.40 -99.14
REMARK 500
REMARK 500 REMARK: NULL
REMARK 500
REMARK 500 GEOMETRY AND STEREOCHEMISTRY
REMARK 500 SUBTOPIC: NON-CIS, NON-TRANS
REMARK 500
REMARK 500 THE FOLLOWING PEPTIDE BONDS DEVIATE SIGNIFICANTLY FROM BOTH
REMARK 500 CIS AND TRANS CONFORMATION. CIS BONDS, IF ANY, ARE LISTED
REMARK 500 ON CISPEP RECORDS. TRANS IS DEFINED AS 180 +/- 30 AND
REMARK 500 CIS IS DEFINED AS 0 +/- 30 DEGREES.
REMARK 500 MODEL OMEGA
REMARK 500 TRP B 197 TYR B 198 147.44
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 A 917 DISTANCE = 6.31 ANGSTROMS
REMARK 525 HOH B 921 DISTANCE = 6.49 ANGSTROMS
REMARK 800
REMARK 800 SITE
REMARK 800 SITE_IDENTIFIER: AC1
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: binding site for residue 4RZ A 401
REMARK 800
REMARK 800 SITE_IDENTIFIER: AC2
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: binding site for residue GOL A 402
REMARK 800
REMARK 800 SITE_IDENTIFIER: AC3
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: binding site for residue 4RZ B 401
REMARK 800
REMARK 800 SITE_IDENTIFIER: AC4
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: binding site for residue GOL B 402
REMARK 900
REMARK 900 RELATED ENTRIES
REMARK 900 RELATED ID: 4ZSM RELATED DB: PDB
REMARK 900 RELATED ID: 4ZSQ RELATED DB: PDB
REMARK 900 RELATED ID: 4ZSR RELATED DB: PDB
DBREF 4ZSP A -47 393 UNP P56817 BACE1_HUMAN 14 454
DBREF 4ZSP B -47 393 UNP P56817 BACE1_HUMAN 14 454
SEQADV 4ZSP MET A -48 UNP P56817 INITIATING METHIONINE
SEQADV 4ZSP MET B -48 UNP P56817 INITIATING METHIONINE
SEQRES 1 A 442 MET ALA GLY VAL LEU PRO ALA HIS GLY THR GLN HIS GLY
SEQRES 2 A 442 ILE ARG LEU PRO LEU ARG SER GLY LEU GLY GLY ALA PRO
SEQRES 3 A 442 LEU GLY LEU ARG LEU PRO ARG GLU THR ASP GLU GLU PRO
SEQRES 4 A 442 GLU GLU PRO GLY ARG ARG GLY SER PHE VAL GLU MET VAL
SEQRES 5 A 442 ASP ASN LEU ARG GLY LYS SER GLY GLN GLY TYR TYR VAL
SEQRES 6 A 442 GLU MET THR VAL GLY SER PRO PRO GLN THR LEU ASN ILE
SEQRES 7 A 442 LEU VAL ASP THR GLY SER SER ASN PHE ALA VAL GLY ALA
SEQRES 8 A 442 ALA PRO HIS PRO PHE LEU HIS ARG TYR TYR GLN ARG GLN
SEQRES 9 A 442 LEU SER SER THR TYR ARG ASP LEU ARG LYS GLY VAL TYR
SEQRES 10 A 442 VAL PRO TYR THR GLN GLY LYS TRP GLU GLY GLU LEU GLY
SEQRES 11 A 442 THR ASP LEU VAL SER ILE PRO HIS GLY PRO ASN VAL THR
SEQRES 12 A 442 VAL ARG ALA ASN ILE ALA ALA ILE THR GLU SER ASP LYS
SEQRES 13 A 442 PHE PHE ILE ASN GLY SER ASN TRP GLU GLY ILE LEU GLY
SEQRES 14 A 442 LEU ALA TYR ALA GLU ILE ALA ARG PRO ASP ASP SER LEU
SEQRES 15 A 442 GLU PRO PHE PHE ASP SER LEU VAL LYS GLN THR HIS VAL
SEQRES 16 A 442 PRO ASN LEU PHE SER LEU GLN LEU CYS GLY ALA GLY PHE
SEQRES 17 A 442 PRO LEU ASN GLN SER GLU VAL LEU ALA SER VAL GLY GLY
SEQRES 18 A 442 SER MET ILE ILE GLY GLY ILE ASP HIS SER LEU TYR THR
SEQRES 19 A 442 GLY SER LEU TRP TYR THR PRO ILE ARG ARG GLU TRP TYR
SEQRES 20 A 442 TYR GLU VAL ILE ILE VAL ARG VAL GLU ILE ASN GLY GLN
SEQRES 21 A 442 ASP LEU LYS MET ASP CYS LYS GLU TYR ASN TYR ASP LYS
SEQRES 22 A 442 SER ILE VAL ASP SER GLY THR THR ASN LEU ARG LEU PRO
SEQRES 23 A 442 LYS LYS VAL PHE GLU ALA ALA VAL LYS SER ILE LYS ALA
SEQRES 24 A 442 ALA SER SER THR GLU LYS PHE PRO ASP GLY PHE TRP LEU
SEQRES 25 A 442 GLY GLU GLN LEU VAL CYS TRP GLN ALA GLY THR THR PRO
SEQRES 26 A 442 TRP ASN ILE PHE PRO VAL ILE SER LEU TYR LEU MET GLY
SEQRES 27 A 442 GLU VAL THR ASN GLN SER PHE ARG ILE THR ILE LEU PRO
SEQRES 28 A 442 GLN GLN TYR LEU ARG PRO VAL GLU ASP VAL ALA THR SER
SEQRES 29 A 442 GLN ASP ASP CYS TYR LYS PHE ALA ILE SER GLN SER SER
SEQRES 30 A 442 THR GLY THR VAL MET GLY ALA VAL ILE MET GLU GLY PHE
SEQRES 31 A 442 TYR VAL VAL PHE ASP ARG ALA ARG LYS ARG ILE GLY PHE
SEQRES 32 A 442 ALA VAL SER ALA CYS HIS VAL HIS ASP GLU PHE ARG THR
SEQRES 33 A 442 ALA ALA VAL GLU GLY PRO PHE VAL THR LEU ASP MET GLU
SEQRES 34 A 442 ASP CYS GLY TYR ASN ILE PRO GLN THR ASP GLU SER THR
SEQRES 1 B 442 MET ALA GLY VAL LEU PRO ALA HIS GLY THR GLN HIS GLY
SEQRES 2 B 442 ILE ARG LEU PRO LEU ARG SER GLY LEU GLY GLY ALA PRO
SEQRES 3 B 442 LEU GLY LEU ARG LEU PRO ARG GLU THR ASP GLU GLU PRO
SEQRES 4 B 442 GLU GLU PRO GLY ARG ARG GLY SER PHE VAL GLU MET VAL
SEQRES 5 B 442 ASP ASN LEU ARG GLY LYS SER GLY GLN GLY TYR TYR VAL
SEQRES 6 B 442 GLU MET THR VAL GLY SER PRO PRO GLN THR LEU ASN ILE
SEQRES 7 B 442 LEU VAL ASP THR GLY SER SER ASN PHE ALA VAL GLY ALA
SEQRES 8 B 442 ALA PRO HIS PRO PHE LEU HIS ARG TYR TYR GLN ARG GLN
SEQRES 9 B 442 LEU SER SER THR TYR ARG ASP LEU ARG LYS GLY VAL TYR
SEQRES 10 B 442 VAL PRO TYR THR GLN GLY LYS TRP GLU GLY GLU LEU GLY
SEQRES 11 B 442 THR ASP LEU VAL SER ILE PRO HIS GLY PRO ASN VAL THR
SEQRES 12 B 442 VAL ARG ALA ASN ILE ALA ALA ILE THR GLU SER ASP LYS
SEQRES 13 B 442 PHE PHE ILE ASN GLY SER ASN TRP GLU GLY ILE LEU GLY
SEQRES 14 B 442 LEU ALA TYR ALA GLU ILE ALA ARG PRO ASP ASP SER LEU
SEQRES 15 B 442 GLU PRO PHE PHE ASP SER LEU VAL LYS GLN THR HIS VAL
SEQRES 16 B 442 PRO ASN LEU PHE SER LEU GLN LEU CYS GLY ALA GLY PHE
SEQRES 17 B 442 PRO LEU ASN GLN SER GLU VAL LEU ALA SER VAL GLY GLY
SEQRES 18 B 442 SER MET ILE ILE GLY GLY ILE ASP HIS SER LEU TYR THR
SEQRES 19 B 442 GLY SER LEU TRP TYR THR PRO ILE ARG ARG GLU TRP TYR
SEQRES 20 B 442 TYR GLU VAL ILE ILE VAL ARG VAL GLU ILE ASN GLY GLN
SEQRES 21 B 442 ASP LEU LYS MET ASP CYS LYS GLU TYR ASN TYR ASP LYS
SEQRES 22 B 442 SER ILE VAL ASP SER GLY THR THR ASN LEU ARG LEU PRO
SEQRES 23 B 442 LYS LYS VAL PHE GLU ALA ALA VAL LYS SER ILE LYS ALA
SEQRES 24 B 442 ALA SER SER THR GLU LYS PHE PRO ASP GLY PHE TRP LEU
SEQRES 25 B 442 GLY GLU GLN LEU VAL CYS TRP GLN ALA GLY THR THR PRO
SEQRES 26 B 442 TRP ASN ILE PHE PRO VAL ILE SER LEU TYR LEU MET GLY
SEQRES 27 B 442 GLU VAL THR ASN GLN SER PHE ARG ILE THR ILE LEU PRO
SEQRES 28 B 442 GLN GLN TYR LEU ARG PRO VAL GLU ASP VAL ALA THR SER
SEQRES 29 B 442 GLN ASP ASP CYS TYR LYS PHE ALA ILE SER GLN SER SER
SEQRES 30 B 442 THR GLY THR VAL MET GLY ALA VAL ILE MET GLU GLY PHE
SEQRES 31 B 442 TYR VAL VAL PHE ASP ARG ALA ARG LYS ARG ILE GLY PHE
SEQRES 32 B 442 ALA VAL SER ALA CYS HIS VAL HIS ASP GLU PHE ARG THR
SEQRES 33 B 442 ALA ALA VAL GLU GLY PRO PHE VAL THR LEU ASP MET GLU
SEQRES 34 B 442 ASP CYS GLY TYR ASN ILE PRO GLN THR ASP GLU SER THR
HET 4RZ A 401 21
HET GOL A 402 6
HET 4RZ B 401 21
HET GOL B 402 6
HETNAM 4RZ N-[(4AS,6S,8AR)-2-AMINO-4A,5,6,7,8,8A-HEXAHYDRO-4H-3,1-
HETNAM 2 4RZ BENZOTHIAZIN-6-YL]-3-CHLOROBENZAMIDE
HETNAM GOL GLYCEROL
HETSYN GOL GLYCERIN; PROPANE-1,2,3-TRIOL
FORMUL 3 4RZ 2(C15 H18 CL N3 O S)
FORMUL 4 GOL 2(C3 H8 O3)
FORMUL 7 HOH *838(H2 O)
HELIX 1 AA1 GLN A 53 SER A 57 5 5
HELIX 2 AA2 TYR A 123 ALA A 127 5 5
HELIX 3 AA3 PRO A 135 THR A 144 1 10
HELIX 4 AA4 ASN A 162 SER A 169 1 8
HELIX 5 AA5 ASP A 180 SER A 182 5 3
HELIX 6 AA6 ASP A 216 TYR A 222 5 7
HELIX 7 AA7 LYS A 238 SER A 252 1 15
HELIX 8 AA8 PRO A 258 LEU A 263 1 6
HELIX 9 AA9 PRO A 276 PHE A 280 5 5
HELIX 10 AB1 LEU A 301 TYR A 305 1 5
HELIX 11 AB2 GLY A 334 GLU A 339 1 6
HELIX 12 AB3 ARG A 347 ARG A 349 5 3
HELIX 13 AB4 ASP A 378 GLY A 383 5 6
HELIX 14 AB5 GLN B 53 SER B 57 5 5
HELIX 15 AB6 TYR B 123 ALA B 127 5 5
HELIX 16 AB7 PRO B 135 THR B 144 1 10
HELIX 17 AB8 ASN B 162 SER B 169 1 8
HELIX 18 AB9 ASP B 180 SER B 182 5 3
HELIX 19 AC1 ASP B 216 TYR B 222 5 7
HELIX 20 AC2 LYS B 238 SER B 252 1 15
HELIX 21 AC3 PRO B 258 LEU B 263 1 6
HELIX 22 AC4 PRO B 276 PHE B 280 5 5
HELIX 23 AC5 LEU B 301 TYR B 305 1 5
HELIX 24 AC6 GLY B 334 GLU B 339 1 6
HELIX 25 AC7 ASP B 378 GLY B 383 5 6
SHEET 1 AA1 8 LEU A 6 LYS A 9 0
SHEET 2 AA1 8 GLY A 13 VAL A 20 -1 O TYR A 15 N ARG A 7
SHEET 3 AA1 8 GLN A 25 ASP A 32 -1 O ILE A 29 N VAL A 16
SHEET 4 AA1 8 GLY A 117 GLY A 120 1 O LEU A 119 N LEU A 30
SHEET 5 AA1 8 PHE A 38 GLY A 41 -1 N ALA A 39 O ILE A 118
SHEET 6 AA1 8 VAL A 95 ASP A 106 1 O ILE A 102 N VAL A 40
SHEET 7 AA1 8 LYS A 75 SER A 86 -1 N GLY A 81 O ILE A 99
SHEET 8 AA1 8 ARG A 61 PRO A 70 -1 N VAL A 69 O TRP A 76
SHEET 1 AA2 4 LEU A 6 LYS A 9 0
SHEET 2 AA2 4 GLY A 13 VAL A 20 -1 O TYR A 15 N ARG A 7
SHEET 3 AA2 4 LYS A 75 SER A 86 -1 O SER A 86 N THR A 19
SHEET 4 AA2 4 ARG A 61 PRO A 70 -1 N VAL A 69 O TRP A 76
SHEET 1 AA3 5 GLY A 172 ILE A 176 0
SHEET 2 AA3 5 PHE A 150 LEU A 154 -1 N GLN A 153 O SER A 173
SHEET 3 AA3 5 PHE A 341 ASP A 346 -1 O VAL A 343 N LEU A 152
SHEET 4 AA3 5 ARG A 351 SER A 357 -1 O ALA A 355 N TYR A 342
SHEET 5 AA3 5 TYR A 184 PRO A 192 -1 N THR A 191 O ILE A 352
SHEET 1 AA4 5 GLU A 200 VAL A 201 0
SHEET 2 AA4 5 SER A 225 VAL A 227 -1 O SER A 225 N VAL A 201
SHEET 3 AA4 5 THR A 331 MET A 333 1 O MET A 333 N ILE A 226
SHEET 4 AA4 5 LEU A 234 PRO A 237 -1 N ARG A 235 O VAL A 332
SHEET 5 AA4 5 ILE A 324 SER A 327 1 O SER A 325 N LEU A 236
SHEET 1 AA5 5 GLN A 211 ASP A 212 0
SHEET 2 AA5 5 ILE A 203 ILE A 208 -1 N ILE A 208 O GLN A 211
SHEET 3 AA5 5 ILE A 283 MET A 288 -1 O TYR A 286 N ARG A 205
SHEET 4 AA5 5 GLN A 294 ILE A 300 -1 O ILE A 300 N ILE A 283
SHEET 5 AA5 5 ALA A 369 VAL A 375 -1 O GLU A 371 N ARG A 297
SHEET 1 AA6 3 VAL A 268 TRP A 270 0
SHEET 2 AA6 3 ASP A 318 PHE A 322 -1 O ASP A 318 N TRP A 270
SHEET 3 AA6 3 LEU A 306 VAL A 309 -1 N ARG A 307 O LYS A 321
SHEET 1 AA7 8 LEU B 6 LYS B 9 0
SHEET 2 AA7 8 GLY B 13 VAL B 20 -1 O TYR B 15 N ARG B 7
SHEET 3 AA7 8 GLN B 25 ASP B 32 -1 O LEU B 27 N MET B 18
SHEET 4 AA7 8 GLY B 117 GLY B 120 1 O LEU B 119 N LEU B 30
SHEET 5 AA7 8 PHE B 38 GLY B 41 -1 N ALA B 39 O ILE B 118
SHEET 6 AA7 8 THR B 94 ASP B 106 1 O ALA B 100 N PHE B 38
SHEET 7 AA7 8 LYS B 75 SER B 86 -1 N GLU B 77 O GLU B 104
SHEET 8 AA7 8 ARG B 61 PRO B 70 -1 N VAL B 69 O TRP B 76
SHEET 1 AA8 4 LEU B 6 LYS B 9 0
SHEET 2 AA8 4 GLY B 13 VAL B 20 -1 O TYR B 15 N ARG B 7
SHEET 3 AA8 4 LYS B 75 SER B 86 -1 O SER B 86 N THR B 19
SHEET 4 AA8 4 ARG B 61 PRO B 70 -1 N VAL B 69 O TRP B 76
SHEET 1 AA9 5 GLY B 172 ILE B 176 0
SHEET 2 AA9 5 PHE B 150 LEU B 154 -1 N GLN B 153 O SER B 173
SHEET 3 AA9 5 PHE B 341 ASP B 346 -1 O PHE B 345 N PHE B 150
SHEET 4 AA9 5 ARG B 351 SER B 357 -1 O ALA B 355 N TYR B 342
SHEET 5 AA9 5 TYR B 184 PRO B 192 -1 N THR B 191 O ILE B 352
SHEET 1 AB1 5 GLN B 211 ASP B 212 0
SHEET 2 AB1 5 ILE B 203 ILE B 208 -1 N ILE B 208 O GLN B 211
SHEET 3 AB1 5 ILE B 283 MET B 288 -1 O TYR B 286 N ARG B 205
SHEET 4 AB1 5 GLN B 294 ILE B 300 -1 O ILE B 300 N ILE B 283
SHEET 5 AB1 5 ALA B 369 VAL B 375 -1 O ALA B 369 N THR B 299
SHEET 1 AB2 4 SER B 225 VAL B 227 0
SHEET 2 AB2 4 THR B 331 MET B 333 1 O MET B 333 N ILE B 226
SHEET 3 AB2 4 LEU B 234 PRO B 237 -1 N ARG B 235 O VAL B 332
SHEET 4 AB2 4 ILE B 324 SER B 327 1 O SER B 325 N LEU B 236
SHEET 1 AB3 3 VAL B 268 TRP B 270 0
SHEET 2 AB3 3 ASP B 318 PHE B 322 -1 O ASP B 318 N TRP B 270
SHEET 3 AB3 3 LEU B 306 VAL B 309 -1 N ARG B 307 O LYS B 321
SSBOND 1 CYS A 155 CYS A 359 1555 1555 2.15
SSBOND 2 CYS A 217 CYS A 382 1555 1555 2.09
SSBOND 3 CYS A 269 CYS A 319 1555 1555 2.11
SSBOND 4 CYS B 155 CYS B 359 1555 1555 2.15
SSBOND 5 CYS B 217 CYS B 382 1555 1555 2.07
SSBOND 6 CYS B 269 CYS B 319 1555 1555 2.10
CISPEP 1 SER A 22 PRO A 23 0 -4.65
CISPEP 2 ARG A 128 PRO A 129 0 4.76
CISPEP 3 TYR A 222 ASP A 223 0 -1.87
CISPEP 4 GLY A 372 PRO A 373 0 0.95
CISPEP 5 SER B 22 PRO B 23 0 -7.82
CISPEP 6 ARG B 128 PRO B 129 0 2.03
CISPEP 7 TYR B 222 ASP B 223 0 -0.30
CISPEP 8 GLY B 372 PRO B 373 0 0.16
SITE 1 AC1 13 SER A 10 GLY A 11 GLN A 12 GLY A 13
SITE 2 AC1 13 ASP A 32 GLY A 34 TYR A 71 TRP A 115
SITE 3 AC1 13 ASP A 228 SER A 229 GLY A 230 THR A 232
SITE 4 AC1 13 HOH A 618
SITE 1 AC2 8 ASP A 318 HOH A 513 HOH A 567 HOH A 729
SITE 2 AC2 8 SER B 58 THR B 59 ARG B 61 ARG B 96
SITE 1 AC3 13 SER B 10 GLY B 11 GLN B 12 GLY B 13
SITE 2 AC3 13 ASP B 32 GLY B 34 TYR B 71 TRP B 115
SITE 3 AC3 13 ASP B 228 SER B 229 GLY B 230 THR B 232
SITE 4 AC3 13 HOH B 544
SITE 1 AC4 8 SER A 58 THR A 59 ARG A 61 ARG A 96
SITE 2 AC4 8 ASP B 318 HOH B 528 HOH B 596 HOH B 635
CRYST1 86.647 91.689 131.205 90.00 90.00 90.00 P 21 21 21 8
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 0.011541 0.000000 0.000000 0.00000
SCALE2 0.000000 0.010906 0.000000 0.00000
SCALE3 0.000000 0.000000 0.007622 0.00000
(ATOM LINES ARE NOT SHOWN.)
END