HEADER HYDROLASE/INHIBITOR 27-JUN-12 4FSL
TITLE CRYSTAL STRUCTURE OF BETA-SITE APP-CLEAVING ENZYME 1 (BACE-DB-MUT)
TITLE 2 COMPLEX WITH N-(N-(4- ACETAMIDO-3-CHLORO-5-METHYLBENZYL)
TITLE 3 CARBAMIMIDOYL)-3-(4- METHOXYPHENYL)-5-METHYL-4-ISOTHIAZOLECARBOXAMIDE
COMPND MOL_ID: 1;
COMPND 2 MOLECULE: BETA-SECRETASE 1;
COMPND 3 CHAIN: A, B, D, E;
COMPND 4 FRAGMENT: UNP RESIDUES 43-453;
COMPND 5 SYNONYM: ASPARTYL PROTEASE 2, ASP2, ASP 2, BETA-SITE AMYLOID
COMPND 6 PRECURSOR PROTEIN CLEAVING ENZYME 1, BETA-SITE APP CLEAVING ENZYME 1,
COMPND 7 MEMAPSIN-2, 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: 469008;
SOURCE 8 EXPRESSION_SYSTEM_STRAIN: BL21(DE3);
SOURCE 9 EXPRESSION_SYSTEM_VECTOR_TYPE: PLASMID
KEYWDS ALZHEIMER'S DISEASE, BETA-SECRETASE, MEMAPSIN 2, BASE, ASPARTIC
KEYWDS 2 PROTEASE, HYDROLASE-INHIBITOR COMPLEX
EXPDTA X-RAY DIFFRACTION
AUTHOR J.K.MUCKELBAUER
REVDAT 5 17-JUL-19 4FSL 1 REMARK
REVDAT 4 13-JUN-18 4FSL 1 REMARK
REVDAT 3 15-NOV-17 4FSL 1 REMARK
REVDAT 2 10-JUL-13 4FSL 1 JRNL
REVDAT 1 10-OCT-12 4FSL 0
JRNL AUTH S.W.GERRITZ,W.ZHAI,S.SHI,S.ZHU,J.H.TOYN,J.E.MEREDITH,
JRNL AUTH 2 L.G.IBEN,C.R.BURTON,C.F.ALBRIGHT,A.C.GOOD,A.J.TEBBEN,
JRNL AUTH 3 J.K.MUCKELBAUER,D.M.CAMAC,W.METZLER,L.S.COOK,R.PADMANABHA,
JRNL AUTH 4 K.A.LENTZ,M.J.SOFIA,M.A.POSS,J.E.MACOR,L.A.THOMPSON
JRNL TITL ACYL GUANIDINE INHIBITORS OF BETA-SECRETASE (BACE-1):
JRNL TITL 2 OPTIMIZATION OF A MICROMOLAR HIT TO A NANOMOLAR LEAD VIA
JRNL TITL 3 ITERATIVE SOLID- AND SOLUTION-PHASE LIBRARY SYNTHESIS
JRNL REF J.MED.CHEM. V. 55 9208 2012
JRNL REFN ISSN 0022-2623
JRNL PMID 23030502
JRNL DOI 10.1021/JM300931Y
REMARK 2
REMARK 2 RESOLUTION. 2.50 ANGSTROMS.
REMARK 3
REMARK 3 REFINEMENT.
REMARK 3 PROGRAM : REFMAC 5.2.0019
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) : 2.50
REMARK 3 RESOLUTION RANGE LOW (ANGSTROMS) : 50.00
REMARK 3 DATA CUTOFF (SIGMA(F)) : 0.000
REMARK 3 COMPLETENESS FOR RANGE (%) : 96.5
REMARK 3 NUMBER OF REFLECTIONS : 66542
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) : 0.227
REMARK 3 R VALUE (WORKING SET) : 0.224
REMARK 3 FREE R VALUE : 0.277
REMARK 3 FREE R VALUE TEST SET SIZE (%) : 5.100
REMARK 3 FREE R VALUE TEST SET COUNT : 3377
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) : 2.50
REMARK 3 BIN RESOLUTION RANGE LOW (A) : NULL
REMARK 3 REFLECTION IN BIN (WORKING SET) : 4284
REMARK 3 BIN COMPLETENESS (WORKING+TEST) (%) : 88.77
REMARK 3 BIN R VALUE (WORKING SET) : 0.2970
REMARK 3 BIN FREE R VALUE SET COUNT : 246
REMARK 3 BIN FREE R VALUE : 0.3590
REMARK 3
REMARK 3 NUMBER OF NON-HYDROGEN ATOMS USED IN REFINEMENT.
REMARK 3 PROTEIN ATOMS : 12156
REMARK 3 NUCLEIC ACID ATOMS : 0
REMARK 3 HETEROGEN ATOMS : 144
REMARK 3 SOLVENT ATOMS : 819
REMARK 3
REMARK 3 B VALUES.
REMARK 3 FROM WILSON PLOT (A**2) : NULL
REMARK 3 MEAN B VALUE (OVERALL, A**2) : 26.36
REMARK 3 OVERALL ANISOTROPIC B VALUE.
REMARK 3 B11 (A**2) : -2.52000
REMARK 3 B22 (A**2) : -1.86000
REMARK 3 B33 (A**2) : 4.51000
REMARK 3 B12 (A**2) : 0.00000
REMARK 3 B13 (A**2) : 0.52000
REMARK 3 B23 (A**2) : 0.00000
REMARK 3
REMARK 3 ESTIMATED OVERALL COORDINATE ERROR.
REMARK 3 ESU BASED ON R VALUE (A): 0.639
REMARK 3 ESU BASED ON FREE R VALUE (A): 0.325
REMARK 3 ESU BASED ON MAXIMUM LIKELIHOOD (A): 0.218
REMARK 3 ESU FOR B VALUES BASED ON MAXIMUM LIKELIHOOD (A**2): 9.853
REMARK 3
REMARK 3 CORRELATION COEFFICIENTS.
REMARK 3 CORRELATION COEFFICIENT FO-FC : 0.936
REMARK 3 CORRELATION COEFFICIENT FO-FC FREE : 0.902
REMARK 3
REMARK 3 RMS DEVIATIONS FROM IDEAL VALUES COUNT RMS WEIGHT
REMARK 3 BOND LENGTHS REFINED ATOMS (A): 12619 ; 0.007 ; 0.022
REMARK 3 BOND LENGTHS OTHERS (A): NULL ; NULL ; NULL
REMARK 3 BOND ANGLES REFINED ATOMS (DEGREES): 17174 ; 1.154 ; 1.958
REMARK 3 BOND ANGLES OTHERS (DEGREES): NULL ; NULL ; NULL
REMARK 3 TORSION ANGLES, PERIOD 1 (DEGREES): 1544 ; 5.612 ; 5.000
REMARK 3 TORSION ANGLES, PERIOD 2 (DEGREES): 576 ;36.086 ;23.958
REMARK 3 TORSION ANGLES, PERIOD 3 (DEGREES): 1976 ;14.724 ;15.000
REMARK 3 TORSION ANGLES, PERIOD 4 (DEGREES): 68 ;14.327 ;15.000
REMARK 3 CHIRAL-CENTER RESTRAINTS (A**3): 1848 ; 0.069 ; 0.200
REMARK 3 GENERAL PLANES REFINED ATOMS (A): 9784 ; 0.003 ; 0.020
REMARK 3 GENERAL PLANES OTHERS (A): NULL ; NULL ; NULL
REMARK 3 NON-BONDED CONTACTS REFINED ATOMS (A): 5905 ; 0.179 ; 0.200
REMARK 3 NON-BONDED CONTACTS OTHERS (A): NULL ; NULL ; NULL
REMARK 3 NON-BONDED TORSION REFINED ATOMS (A): 8558 ; 0.305 ; 0.200
REMARK 3 NON-BONDED TORSION OTHERS (A): NULL ; NULL ; NULL
REMARK 3 H-BOND (X...Y) REFINED ATOMS (A): 1070 ; 0.125 ; 0.200
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): 101 ; 0.222 ; 0.200
REMARK 3 SYMMETRY VDW OTHERS (A): NULL ; NULL ; NULL
REMARK 3 SYMMETRY H-BOND REFINED ATOMS (A): 22 ; 0.099 ; 0.200
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): 7715 ; 0.318 ; 1.500
REMARK 3 MAIN-CHAIN BOND OTHER ATOMS (A**2): NULL ; NULL ; NULL
REMARK 3 MAIN-CHAIN ANGLE REFINED ATOMS (A**2): 12419 ; 0.589 ; 2.000
REMARK 3 MAIN-CHAIN ANGLE OTHER ATOMS (A**2): NULL ; NULL ; NULL
REMARK 3 SIDE-CHAIN BOND REFINED ATOMS (A**2): 5572 ; 0.623 ; 3.000
REMARK 3 SIDE-CHAIN BOND OTHER ATOMS (A**2): NULL ; NULL ; NULL
REMARK 3 SIDE-CHAIN ANGLE REFINED ATOMS (A**2): 4755 ; 1.073 ; 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 : 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 ADDED IN THE RIDING
REMARK 3 POSITIONS
REMARK 4
REMARK 4 4FSL COMPLIES WITH FORMAT V. 3.30, 13-JUL-11
REMARK 100
REMARK 100 THIS ENTRY HAS BEEN PROCESSED BY RCSB ON 06-JUL-12.
REMARK 100 THE DEPOSITION ID IS D_1000073303.
REMARK 200
REMARK 200 EXPERIMENTAL DETAILS
REMARK 200 EXPERIMENT TYPE : X-RAY DIFFRACTION
REMARK 200 DATE OF DATA COLLECTION : 29-APR-05
REMARK 200 TEMPERATURE (KELVIN) : 100.0
REMARK 200 PH : 6.2
REMARK 200 NUMBER OF CRYSTALS USED : 1
REMARK 200
REMARK 200 SYNCHROTRON (Y/N) : N
REMARK 200 RADIATION SOURCE : ROTATING ANODE
REMARK 200 BEAMLINE : NULL
REMARK 200 X-RAY GENERATOR MODEL : RIGAKU
REMARK 200 MONOCHROMATIC OR LAUE (M/L) : M
REMARK 200 WAVELENGTH OR RANGE (A) : 1.54000
REMARK 200 MONOCHROMATOR : NULL
REMARK 200 OPTICS : MICROMAX CONFOCAL
REMARK 200
REMARK 200 DETECTOR TYPE : CCD
REMARK 200 DETECTOR MANUFACTURER : RIGAKU SATURN 92
REMARK 200 INTENSITY-INTEGRATION SOFTWARE : DENZO, HKL-2000
REMARK 200 DATA SCALING SOFTWARE : SCALEPACK, HKL-2000
REMARK 200
REMARK 200 NUMBER OF UNIQUE REFLECTIONS : 66645
REMARK 200 RESOLUTION RANGE HIGH (A) : 2.500
REMARK 200 RESOLUTION RANGE LOW (A) : 50.000
REMARK 200 REJECTION CRITERIA (SIGMA(I)) : NULL
REMARK 200
REMARK 200 OVERALL.
REMARK 200 COMPLETENESS FOR RANGE (%) : 96.8
REMARK 200 DATA REDUNDANCY : 3.600
REMARK 200 R MERGE (I) : 0.08700
REMARK 200 R SYM (I) : NULL
REMARK 200 <I/SIGMA(I)> FOR THE DATA SET : 7.7000
REMARK 200
REMARK 200 IN THE HIGHEST RESOLUTION SHELL.
REMARK 200 HIGHEST RESOLUTION SHELL, RANGE HIGH (A) : 2.50
REMARK 200 HIGHEST RESOLUTION SHELL, RANGE LOW (A) : 2.59
REMARK 200 COMPLETENESS FOR SHELL (%) : 91.1
REMARK 200 DATA REDUNDANCY IN SHELL : 3.20
REMARK 200 R MERGE FOR SHELL (I) : 0.47200
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: MOLECULAR REPLACEMENT
REMARK 200 SOFTWARE USED: CNS
REMARK 200 STARTING MODEL: NULL
REMARK 200
REMARK 200 REMARK: NULL
REMARK 280
REMARK 280 CRYSTAL
REMARK 280 SOLVENT CONTENT, VS (%): 55.53
REMARK 280 MATTHEWS COEFFICIENT, VM (ANGSTROMS**3/DA): 2.77
REMARK 280
REMARK 280 CRYSTALLIZATION CONDITIONS: 35% PEG8K, 0.2 M AMMONIUM SULFATE, PH
REMARK 280 6.2, VAPOR DIFFUSION, HANGING DROP, TEMPERATURE 298K
REMARK 290
REMARK 290 CRYSTALLOGRAPHIC SYMMETRY
REMARK 290 SYMMETRY OPERATORS FOR SPACE GROUP: P 1 21 1
REMARK 290
REMARK 290 SYMOP SYMMETRY
REMARK 290 NNNMMM OPERATOR
REMARK 290 1555 X,Y,Z
REMARK 290 2555 -X,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 0.00000
REMARK 290 SMTRY2 2 0.000000 1.000000 0.000000 65.58850
REMARK 290 SMTRY3 2 0.000000 0.000000 -1.000000 0.00000
REMARK 290
REMARK 290 REMARK: NULL
REMARK 300
REMARK 300 BIOMOLECULE: 1, 2, 3, 4
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 350
REMARK 350 BIOMOLECULE: 3
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: D
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: 4
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: E
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 LEU A 30
REMARK 465 PRO A 31
REMARK 465 ARG A 32
REMARK 465 GLU A 33
REMARK 465 THR A 34
REMARK 465 ASP A 35
REMARK 465 GLU A 36
REMARK 465 GLU A 37
REMARK 465 PRO A 38
REMARK 465 GLU A 39
REMARK 465 GLU A 40
REMARK 465 PRO A 41
REMARK 465 GLY A 42
REMARK 465 LYS A 43
REMARK 465 LYS A 44
REMARK 465 GLY A 45
REMARK 465 SER A 46
REMARK 465 ILE A 434
REMARK 465 PRO A 435
REMARK 465 GLN A 436
REMARK 465 THR A 437
REMARK 465 ASP A 438
REMARK 465 GLU A 439
REMARK 465 SER A 440
REMARK 465 THR A 441
REMARK 465 LEU B 30
REMARK 465 PRO B 31
REMARK 465 ARG B 32
REMARK 465 GLU B 33
REMARK 465 THR B 34
REMARK 465 ASP B 35
REMARK 465 GLU B 36
REMARK 465 GLU B 37
REMARK 465 PRO B 38
REMARK 465 GLU B 39
REMARK 465 GLU B 40
REMARK 465 PRO B 41
REMARK 465 GLY B 42
REMARK 465 LYS B 43
REMARK 465 LYS B 44
REMARK 465 GLY B 45
REMARK 465 SER B 46
REMARK 465 ILE B 434
REMARK 465 PRO B 435
REMARK 465 GLN B 436
REMARK 465 THR B 437
REMARK 465 ASP B 438
REMARK 465 GLU B 439
REMARK 465 SER B 440
REMARK 465 THR B 441
REMARK 465 LEU D 30
REMARK 465 PRO D 31
REMARK 465 ARG D 32
REMARK 465 GLU D 33
REMARK 465 THR D 34
REMARK 465 ASP D 35
REMARK 465 GLU D 36
REMARK 465 GLU D 37
REMARK 465 PRO D 38
REMARK 465 GLU D 39
REMARK 465 GLU D 40
REMARK 465 PRO D 41
REMARK 465 GLY D 42
REMARK 465 LYS D 43
REMARK 465 LYS D 44
REMARK 465 GLY D 45
REMARK 465 SER D 46
REMARK 465 ILE D 434
REMARK 465 PRO D 435
REMARK 465 GLN D 436
REMARK 465 THR D 437
REMARK 465 ASP D 438
REMARK 465 GLU D 439
REMARK 465 SER D 440
REMARK 465 THR D 441
REMARK 465 LEU E 30
REMARK 465 PRO E 31
REMARK 465 ARG E 32
REMARK 465 GLU E 33
REMARK 465 THR E 34
REMARK 465 ASP E 35
REMARK 465 GLU E 36
REMARK 465 GLU E 37
REMARK 465 PRO E 38
REMARK 465 GLU E 39
REMARK 465 GLU E 40
REMARK 465 PRO E 41
REMARK 465 GLY E 42
REMARK 465 LYS E 43
REMARK 465 LYS E 44
REMARK 465 GLY E 45
REMARK 465 SER E 46
REMARK 465 ILE E 434
REMARK 465 PRO E 435
REMARK 465 GLN E 436
REMARK 465 THR E 437
REMARK 465 ASP E 438
REMARK 465 GLU E 439
REMARK 465 SER E 440
REMARK 465 THR E 441
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 LYS A 304 CG CD CE NZ
REMARK 470 VAL A 360 CG1 CG2
REMARK 470 VAL B 360 CG1 CG2
REMARK 470 THR B 362 OG1 CG2
REMARK 470 VAL E 360 CG1 CG2
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 E 798 O HOH E 805 2.19
REMARK 500
REMARK 500 REMARK: NULL
REMARK 500
REMARK 500 GEOMETRY AND STEREOCHEMISTRY
REMARK 500 SUBTOPIC: COVALENT BOND LENGTHS
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,2(A3,1X,A1,I4,A1,1X,A4,3X),1X,F6.3)
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 RES CSSEQI ATM2 DEVIATION
REMARK 500 ASP B 80 CG ASP B 80 OD2 0.166
REMARK 500
REMARK 500 REMARK: NULL
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 ASP B 80 CB - CG - OD1 ANGL. DEV. = 11.1 DEGREES
REMARK 500 ASP B 80 CB - CG - OD2 ANGL. DEV. = -6.9 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 TRP A 245 -75.95 -137.37
REMARK 500 THR A 362 29.03 47.22
REMARK 500 SER A 363 -167.54 -71.92
REMARK 500 HIS B 137 40.53 -98.67
REMARK 500 TRP B 245 -82.15 -135.76
REMARK 500 THR B 362 19.16 51.16
REMARK 500 SER B 363 -177.17 -60.77
REMARK 500 ALA B 371 32.48 -93.55
REMARK 500 ASP B 411 -169.59 -115.10
REMARK 500 HIS D 137 49.82 -94.83
REMARK 500 TRP D 245 -79.27 -136.41
REMARK 500 THR D 302 -18.91 -46.30
REMARK 500 ALA D 320 119.48 -36.26
REMARK 500 ASN D 341 14.08 57.83
REMARK 500 THR D 362 13.28 57.52
REMARK 500 SER D 363 -174.67 -66.52
REMARK 500 ALA D 371 30.13 -99.98
REMARK 500 ARG E 112 55.18 34.88
REMARK 500 HIS E 137 51.88 -104.62
REMARK 500 TRP E 245 -82.37 -134.63
REMARK 500 THR E 362 29.49 47.12
REMARK 500 SER E 363 -172.72 -69.50
REMARK 500 ALA E 371 36.94 -95.17
REMARK 500
REMARK 500 REMARK: NULL
REMARK 800
REMARK 800 SITE
REMARK 800 SITE_IDENTIFIER: AC1
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: BINDING SITE FOR RESIDUE 0VB A 501
REMARK 800
REMARK 800 SITE_IDENTIFIER: AC2
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: BINDING SITE FOR RESIDUE IOD A 502
REMARK 800
REMARK 800 SITE_IDENTIFIER: AC3
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: BINDING SITE FOR RESIDUE IOD A 503
REMARK 800
REMARK 800 SITE_IDENTIFIER: AC4
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: BINDING SITE FOR RESIDUE 0VB B 501
REMARK 800
REMARK 800 SITE_IDENTIFIER: AC5
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: BINDING SITE FOR RESIDUE IOD B 502
REMARK 800
REMARK 800 SITE_IDENTIFIER: AC6
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: BINDING SITE FOR RESIDUE IOD B 503
REMARK 800
REMARK 800 SITE_IDENTIFIER: AC7
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: BINDING SITE FOR RESIDUE 0VB D 501
REMARK 800
REMARK 800 SITE_IDENTIFIER: AC8
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: BINDING SITE FOR RESIDUE IOD D 502
REMARK 800
REMARK 800 SITE_IDENTIFIER: AC9
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: BINDING SITE FOR RESIDUE IOD D 503
REMARK 800
REMARK 800 SITE_IDENTIFIER: BC1
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: BINDING SITE FOR RESIDUE 0VB E 501
REMARK 800
REMARK 800 SITE_IDENTIFIER: BC2
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: BINDING SITE FOR RESIDUE IOD E 502
REMARK 800
REMARK 800 SITE_IDENTIFIER: BC3
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: BINDING SITE FOR RESIDUE IOD E 503
REMARK 800
REMARK 800 SITE_IDENTIFIER: BC4
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: BINDING SITE FOR RESIDUE IOD E 504
REMARK 900
REMARK 900 RELATED ENTRIES
REMARK 900 RELATED ID: 4FSE RELATED DB: PDB
DBREF 4FSL A 30 440 UNP P56817 BACE1_HUMAN 43 453
DBREF 4FSL B 30 440 UNP P56817 BACE1_HUMAN 43 453
DBREF 4FSL D 30 440 UNP P56817 BACE1_HUMAN 43 453
DBREF 4FSL E 30 440 UNP P56817 BACE1_HUMAN 43 453
SEQADV 4FSL LYS A 43 UNP P56817 ARG 56 CONFLICT
SEQADV 4FSL LYS A 44 UNP P56817 ARG 57 CONFLICT
SEQADV 4FSL THR A 441 UNP P56817 EXPRESSION TAG
SEQADV 4FSL LYS B 43 UNP P56817 ARG 56 CONFLICT
SEQADV 4FSL LYS B 44 UNP P56817 ARG 57 CONFLICT
SEQADV 4FSL THR B 441 UNP P56817 EXPRESSION TAG
SEQADV 4FSL LYS D 43 UNP P56817 ARG 56 CONFLICT
SEQADV 4FSL LYS D 44 UNP P56817 ARG 57 CONFLICT
SEQADV 4FSL THR D 441 UNP P56817 EXPRESSION TAG
SEQADV 4FSL LYS E 43 UNP P56817 ARG 56 CONFLICT
SEQADV 4FSL LYS E 44 UNP P56817 ARG 57 CONFLICT
SEQADV 4FSL THR E 441 UNP P56817 EXPRESSION TAG
SEQRES 1 A 412 LEU PRO ARG GLU THR ASP GLU GLU PRO GLU GLU PRO GLY
SEQRES 2 A 412 LYS LYS GLY SER PHE VAL GLU MET VAL ASP ASN LEU ARG
SEQRES 3 A 412 GLY LYS SER GLY GLN GLY TYR TYR VAL GLU MET THR VAL
SEQRES 4 A 412 GLY SER PRO PRO GLN THR LEU ASN ILE LEU VAL ASP THR
SEQRES 5 A 412 GLY SER SER ASN PHE ALA VAL GLY ALA ALA PRO HIS PRO
SEQRES 6 A 412 PHE LEU HIS ARG TYR TYR GLN ARG GLN LEU SER SER THR
SEQRES 7 A 412 TYR ARG ASP LEU ARG LYS GLY VAL TYR VAL PRO TYR THR
SEQRES 8 A 412 GLN GLY LYS TRP GLU GLY GLU LEU GLY THR ASP LEU VAL
SEQRES 9 A 412 SER ILE PRO HIS GLY PRO ASN VAL THR VAL ARG ALA ASN
SEQRES 10 A 412 ILE ALA ALA ILE THR GLU SER ASP LYS PHE PHE ILE ASN
SEQRES 11 A 412 GLY SER ASN TRP GLU GLY ILE LEU GLY LEU ALA TYR ALA
SEQRES 12 A 412 GLU ILE ALA ARG PRO ASP ASP SER LEU GLU PRO PHE PHE
SEQRES 13 A 412 ASP SER LEU VAL LYS GLN THR HIS VAL PRO ASN LEU PHE
SEQRES 14 A 412 SER LEU GLN LEU CYS GLY ALA GLY PHE PRO LEU ASN GLN
SEQRES 15 A 412 SER GLU VAL LEU ALA SER VAL GLY GLY SER MET ILE ILE
SEQRES 16 A 412 GLY GLY ILE ASP HIS SER LEU TYR THR GLY SER LEU TRP
SEQRES 17 A 412 TYR THR PRO ILE ARG ARG GLU TRP TYR TYR GLU VAL ILE
SEQRES 18 A 412 ILE VAL ARG VAL GLU ILE ASN GLY GLN ASP LEU LYS MET
SEQRES 19 A 412 ASP CYS LYS GLU TYR ASN TYR ASP LYS SER ILE VAL ASP
SEQRES 20 A 412 SER GLY THR THR ASN LEU ARG LEU PRO LYS LYS VAL PHE
SEQRES 21 A 412 GLU ALA ALA VAL LYS SER ILE LYS ALA ALA SER SER THR
SEQRES 22 A 412 GLU LYS PHE PRO ASP GLY PHE TRP LEU GLY GLU GLN LEU
SEQRES 23 A 412 VAL CYS TRP GLN ALA GLY THR THR PRO TRP ASN ILE PHE
SEQRES 24 A 412 PRO VAL ILE SER LEU TYR LEU MET GLY GLU VAL THR ASN
SEQRES 25 A 412 GLN SER PHE ARG ILE THR ILE LEU PRO GLN GLN TYR LEU
SEQRES 26 A 412 ARG PRO VAL GLU ASP VAL ALA THR SER GLN ASP ASP CYS
SEQRES 27 A 412 TYR LYS PHE ALA ILE SER GLN SER SER THR GLY THR VAL
SEQRES 28 A 412 MET GLY ALA VAL ILE MET GLU GLY PHE TYR VAL VAL PHE
SEQRES 29 A 412 ASP ARG ALA ARG LYS ARG ILE GLY PHE ALA VAL SER ALA
SEQRES 30 A 412 CYS HIS VAL HIS ASP GLU PHE ARG THR ALA ALA VAL GLU
SEQRES 31 A 412 GLY PRO PHE VAL THR LEU ASP MET GLU ASP CYS GLY TYR
SEQRES 32 A 412 ASN ILE PRO GLN THR ASP GLU SER THR
SEQRES 1 B 412 LEU PRO ARG GLU THR ASP GLU GLU PRO GLU GLU PRO GLY
SEQRES 2 B 412 LYS LYS GLY SER PHE VAL GLU MET VAL ASP ASN LEU ARG
SEQRES 3 B 412 GLY LYS SER GLY GLN GLY TYR TYR VAL GLU MET THR VAL
SEQRES 4 B 412 GLY SER PRO PRO GLN THR LEU ASN ILE LEU VAL ASP THR
SEQRES 5 B 412 GLY SER SER ASN PHE ALA VAL GLY ALA ALA PRO HIS PRO
SEQRES 6 B 412 PHE LEU HIS ARG TYR TYR GLN ARG GLN LEU SER SER THR
SEQRES 7 B 412 TYR ARG ASP LEU ARG LYS GLY VAL TYR VAL PRO TYR THR
SEQRES 8 B 412 GLN GLY LYS TRP GLU GLY GLU LEU GLY THR ASP LEU VAL
SEQRES 9 B 412 SER ILE PRO HIS GLY PRO ASN VAL THR VAL ARG ALA ASN
SEQRES 10 B 412 ILE ALA ALA ILE THR GLU SER ASP LYS PHE PHE ILE ASN
SEQRES 11 B 412 GLY SER ASN TRP GLU GLY ILE LEU GLY LEU ALA TYR ALA
SEQRES 12 B 412 GLU ILE ALA ARG PRO ASP ASP SER LEU GLU PRO PHE PHE
SEQRES 13 B 412 ASP SER LEU VAL LYS GLN THR HIS VAL PRO ASN LEU PHE
SEQRES 14 B 412 SER LEU GLN LEU CYS GLY ALA GLY PHE PRO LEU ASN GLN
SEQRES 15 B 412 SER GLU VAL LEU ALA SER VAL GLY GLY SER MET ILE ILE
SEQRES 16 B 412 GLY GLY ILE ASP HIS SER LEU TYR THR GLY SER LEU TRP
SEQRES 17 B 412 TYR THR PRO ILE ARG ARG GLU TRP TYR TYR GLU VAL ILE
SEQRES 18 B 412 ILE VAL ARG VAL GLU ILE ASN GLY GLN ASP LEU LYS MET
SEQRES 19 B 412 ASP CYS LYS GLU TYR ASN TYR ASP LYS SER ILE VAL ASP
SEQRES 20 B 412 SER GLY THR THR ASN LEU ARG LEU PRO LYS LYS VAL PHE
SEQRES 21 B 412 GLU ALA ALA VAL LYS SER ILE LYS ALA ALA SER SER THR
SEQRES 22 B 412 GLU LYS PHE PRO ASP GLY PHE TRP LEU GLY GLU GLN LEU
SEQRES 23 B 412 VAL CYS TRP GLN ALA GLY THR THR PRO TRP ASN ILE PHE
SEQRES 24 B 412 PRO VAL ILE SER LEU TYR LEU MET GLY GLU VAL THR ASN
SEQRES 25 B 412 GLN SER PHE ARG ILE THR ILE LEU PRO GLN GLN TYR LEU
SEQRES 26 B 412 ARG PRO VAL GLU ASP VAL ALA THR SER GLN ASP ASP CYS
SEQRES 27 B 412 TYR LYS PHE ALA ILE SER GLN SER SER THR GLY THR VAL
SEQRES 28 B 412 MET GLY ALA VAL ILE MET GLU GLY PHE TYR VAL VAL PHE
SEQRES 29 B 412 ASP ARG ALA ARG LYS ARG ILE GLY PHE ALA VAL SER ALA
SEQRES 30 B 412 CYS HIS VAL HIS ASP GLU PHE ARG THR ALA ALA VAL GLU
SEQRES 31 B 412 GLY PRO PHE VAL THR LEU ASP MET GLU ASP CYS GLY TYR
SEQRES 32 B 412 ASN ILE PRO GLN THR ASP GLU SER THR
SEQRES 1 D 412 LEU PRO ARG GLU THR ASP GLU GLU PRO GLU GLU PRO GLY
SEQRES 2 D 412 LYS LYS GLY SER PHE VAL GLU MET VAL ASP ASN LEU ARG
SEQRES 3 D 412 GLY LYS SER GLY GLN GLY TYR TYR VAL GLU MET THR VAL
SEQRES 4 D 412 GLY SER PRO PRO GLN THR LEU ASN ILE LEU VAL ASP THR
SEQRES 5 D 412 GLY SER SER ASN PHE ALA VAL GLY ALA ALA PRO HIS PRO
SEQRES 6 D 412 PHE LEU HIS ARG TYR TYR GLN ARG GLN LEU SER SER THR
SEQRES 7 D 412 TYR ARG ASP LEU ARG LYS GLY VAL TYR VAL PRO TYR THR
SEQRES 8 D 412 GLN GLY LYS TRP GLU GLY GLU LEU GLY THR ASP LEU VAL
SEQRES 9 D 412 SER ILE PRO HIS GLY PRO ASN VAL THR VAL ARG ALA ASN
SEQRES 10 D 412 ILE ALA ALA ILE THR GLU SER ASP LYS PHE PHE ILE ASN
SEQRES 11 D 412 GLY SER ASN TRP GLU GLY ILE LEU GLY LEU ALA TYR ALA
SEQRES 12 D 412 GLU ILE ALA ARG PRO ASP ASP SER LEU GLU PRO PHE PHE
SEQRES 13 D 412 ASP SER LEU VAL LYS GLN THR HIS VAL PRO ASN LEU PHE
SEQRES 14 D 412 SER LEU GLN LEU CYS GLY ALA GLY PHE PRO LEU ASN GLN
SEQRES 15 D 412 SER GLU VAL LEU ALA SER VAL GLY GLY SER MET ILE ILE
SEQRES 16 D 412 GLY GLY ILE ASP HIS SER LEU TYR THR GLY SER LEU TRP
SEQRES 17 D 412 TYR THR PRO ILE ARG ARG GLU TRP TYR TYR GLU VAL ILE
SEQRES 18 D 412 ILE VAL ARG VAL GLU ILE ASN GLY GLN ASP LEU LYS MET
SEQRES 19 D 412 ASP CYS LYS GLU TYR ASN TYR ASP LYS SER ILE VAL ASP
SEQRES 20 D 412 SER GLY THR THR ASN LEU ARG LEU PRO LYS LYS VAL PHE
SEQRES 21 D 412 GLU ALA ALA VAL LYS SER ILE LYS ALA ALA SER SER THR
SEQRES 22 D 412 GLU LYS PHE PRO ASP GLY PHE TRP LEU GLY GLU GLN LEU
SEQRES 23 D 412 VAL CYS TRP GLN ALA GLY THR THR PRO TRP ASN ILE PHE
SEQRES 24 D 412 PRO VAL ILE SER LEU TYR LEU MET GLY GLU VAL THR ASN
SEQRES 25 D 412 GLN SER PHE ARG ILE THR ILE LEU PRO GLN GLN TYR LEU
SEQRES 26 D 412 ARG PRO VAL GLU ASP VAL ALA THR SER GLN ASP ASP CYS
SEQRES 27 D 412 TYR LYS PHE ALA ILE SER GLN SER SER THR GLY THR VAL
SEQRES 28 D 412 MET GLY ALA VAL ILE MET GLU GLY PHE TYR VAL VAL PHE
SEQRES 29 D 412 ASP ARG ALA ARG LYS ARG ILE GLY PHE ALA VAL SER ALA
SEQRES 30 D 412 CYS HIS VAL HIS ASP GLU PHE ARG THR ALA ALA VAL GLU
SEQRES 31 D 412 GLY PRO PHE VAL THR LEU ASP MET GLU ASP CYS GLY TYR
SEQRES 32 D 412 ASN ILE PRO GLN THR ASP GLU SER THR
SEQRES 1 E 412 LEU PRO ARG GLU THR ASP GLU GLU PRO GLU GLU PRO GLY
SEQRES 2 E 412 LYS LYS GLY SER PHE VAL GLU MET VAL ASP ASN LEU ARG
SEQRES 3 E 412 GLY LYS SER GLY GLN GLY TYR TYR VAL GLU MET THR VAL
SEQRES 4 E 412 GLY SER PRO PRO GLN THR LEU ASN ILE LEU VAL ASP THR
SEQRES 5 E 412 GLY SER SER ASN PHE ALA VAL GLY ALA ALA PRO HIS PRO
SEQRES 6 E 412 PHE LEU HIS ARG TYR TYR GLN ARG GLN LEU SER SER THR
SEQRES 7 E 412 TYR ARG ASP LEU ARG LYS GLY VAL TYR VAL PRO TYR THR
SEQRES 8 E 412 GLN GLY LYS TRP GLU GLY GLU LEU GLY THR ASP LEU VAL
SEQRES 9 E 412 SER ILE PRO HIS GLY PRO ASN VAL THR VAL ARG ALA ASN
SEQRES 10 E 412 ILE ALA ALA ILE THR GLU SER ASP LYS PHE PHE ILE ASN
SEQRES 11 E 412 GLY SER ASN TRP GLU GLY ILE LEU GLY LEU ALA TYR ALA
SEQRES 12 E 412 GLU ILE ALA ARG PRO ASP ASP SER LEU GLU PRO PHE PHE
SEQRES 13 E 412 ASP SER LEU VAL LYS GLN THR HIS VAL PRO ASN LEU PHE
SEQRES 14 E 412 SER LEU GLN LEU CYS GLY ALA GLY PHE PRO LEU ASN GLN
SEQRES 15 E 412 SER GLU VAL LEU ALA SER VAL GLY GLY SER MET ILE ILE
SEQRES 16 E 412 GLY GLY ILE ASP HIS SER LEU TYR THR GLY SER LEU TRP
SEQRES 17 E 412 TYR THR PRO ILE ARG ARG GLU TRP TYR TYR GLU VAL ILE
SEQRES 18 E 412 ILE VAL ARG VAL GLU ILE ASN GLY GLN ASP LEU LYS MET
SEQRES 19 E 412 ASP CYS LYS GLU TYR ASN TYR ASP LYS SER ILE VAL ASP
SEQRES 20 E 412 SER GLY THR THR ASN LEU ARG LEU PRO LYS LYS VAL PHE
SEQRES 21 E 412 GLU ALA ALA VAL LYS SER ILE LYS ALA ALA SER SER THR
SEQRES 22 E 412 GLU LYS PHE PRO ASP GLY PHE TRP LEU GLY GLU GLN LEU
SEQRES 23 E 412 VAL CYS TRP GLN ALA GLY THR THR PRO TRP ASN ILE PHE
SEQRES 24 E 412 PRO VAL ILE SER LEU TYR LEU MET GLY GLU VAL THR ASN
SEQRES 25 E 412 GLN SER PHE ARG ILE THR ILE LEU PRO GLN GLN TYR LEU
SEQRES 26 E 412 ARG PRO VAL GLU ASP VAL ALA THR SER GLN ASP ASP CYS
SEQRES 27 E 412 TYR LYS PHE ALA ILE SER GLN SER SER THR GLY THR VAL
SEQRES 28 E 412 MET GLY ALA VAL ILE MET GLU GLY PHE TYR VAL VAL PHE
SEQRES 29 E 412 ASP ARG ALA ARG LYS ARG ILE GLY PHE ALA VAL SER ALA
SEQRES 30 E 412 CYS HIS VAL HIS ASP GLU PHE ARG THR ALA ALA VAL GLU
SEQRES 31 E 412 GLY PRO PHE VAL THR LEU ASP MET GLU ASP CYS GLY TYR
SEQRES 32 E 412 ASN ILE PRO GLN THR ASP GLU SER THR
HET 0VB A 501 33
HET IOD A 502 1
HET IOD A 503 1
HET IOD A 504 1
HET 0VB B 501 33
HET IOD B 502 1
HET IOD B 503 1
HET IOD B 504 1
HET 0VB D 501 33
HET IOD D 502 1
HET IOD D 503 1
HET IOD D 504 1
HET 0VB E 501 33
HET IOD E 502 1
HET IOD E 503 1
HET IOD E 504 1
HETNAM 0VB N-{N-[4-(ACETYLAMINO)-3-CHLORO-5-
HETNAM 2 0VB METHYLBENZYL]CARBAMIMIDOYL}-3-(4-METHOXYPHENYL)-5-
HETNAM 3 0VB METHYL-1,2-THIAZOLE-4-CARBOXAMIDE
HETNAM IOD IODIDE ION
FORMUL 5 0VB 4(C23 H24 CL N5 O3 S)
FORMUL 6 IOD 12(I 1-)
FORMUL 21 HOH *819(H2 O)
HELIX 1 1 GLN A 101 SER A 105 5 5
HELIX 2 2 TYR A 171 ALA A 175 5 5
HELIX 3 3 PRO A 183 THR A 192 1 10
HELIX 4 4 ASN A 210 SER A 217 1 8
HELIX 5 5 ASP A 228 SER A 230 5 3
HELIX 6 6 ASP A 264 TYR A 270 5 7
HELIX 7 7 LYS A 286 SER A 300 1 15
HELIX 8 8 PRO A 324 PHE A 328 5 5
HELIX 9 9 LEU A 349 TYR A 353 1 5
HELIX 10 10 GLY A 382 GLU A 387 1 6
HELIX 11 11 ARG A 395 ARG A 397 5 3
HELIX 12 12 ASP A 426 GLY A 431 5 6
HELIX 13 13 GLN B 101 SER B 105 5 5
HELIX 14 14 TYR B 171 ALA B 175 5 5
HELIX 15 15 PRO B 183 THR B 192 1 10
HELIX 16 16 ASN B 210 SER B 217 1 8
HELIX 17 17 ASP B 228 SER B 230 5 3
HELIX 18 18 ASP B 264 TYR B 270 5 7
HELIX 19 19 LYS B 286 SER B 300 1 15
HELIX 20 20 PRO B 306 LEU B 311 1 6
HELIX 21 21 PRO B 324 PHE B 328 5 5
HELIX 22 22 LEU B 349 TYR B 353 1 5
HELIX 23 23 GLY B 382 GLU B 387 1 6
HELIX 24 24 ASP B 426 GLY B 431 5 6
HELIX 25 25 GLN D 101 SER D 105 5 5
HELIX 26 26 TYR D 171 ALA D 175 5 5
HELIX 27 27 PRO D 183 THR D 192 1 10
HELIX 28 28 ASN D 210 SER D 217 1 8
HELIX 29 29 ASP D 228 SER D 230 5 3
HELIX 30 30 ASP D 264 TYR D 270 5 7
HELIX 31 31 LYS D 286 SER D 300 1 15
HELIX 32 32 PRO D 324 PHE D 328 5 5
HELIX 33 33 LEU D 349 TYR D 353 1 5
HELIX 34 34 GLY D 382 GLU D 387 1 6
HELIX 35 35 ARG D 395 ARG D 397 5 3
HELIX 36 36 ASP D 426 GLY D 431 5 6
HELIX 37 37 GLN E 101 SER E 105 5 5
HELIX 38 38 TYR E 171 ALA E 175 5 5
HELIX 39 39 PRO E 183 THR E 192 1 10
HELIX 40 40 ASN E 210 SER E 217 1 8
HELIX 41 41 ASP E 264 TYR E 270 5 7
HELIX 42 42 LYS E 286 SER E 300 1 15
HELIX 43 43 PRO E 306 LEU E 311 1 6
HELIX 44 44 PRO E 324 PHE E 328 5 5
HELIX 45 45 LEU E 349 TYR E 353 1 5
HELIX 46 46 GLY E 382 GLU E 387 1 6
HELIX 47 47 ASP E 426 GLY E 431 5 6
SHEET 1 A 8 LEU A 54 LYS A 57 0
SHEET 2 A 8 GLY A 61 VAL A 68 -1 O TYR A 63 N ARG A 55
SHEET 3 A 8 GLN A 73 ASP A 80 -1 O ILE A 77 N VAL A 64
SHEET 4 A 8 GLY A 165 GLY A 168 1 O LEU A 167 N LEU A 78
SHEET 5 A 8 PHE A 86 GLY A 89 -1 N ALA A 87 O ILE A 166
SHEET 6 A 8 VAL A 143 ASP A 154 1 O ILE A 150 N VAL A 88
SHEET 7 A 8 LYS A 123 SER A 134 -1 N GLY A 129 O ILE A 147
SHEET 8 A 8 ARG A 109 PRO A 118 -1 N VAL A 117 O TRP A 124
SHEET 1 B 4 LEU A 54 LYS A 57 0
SHEET 2 B 4 GLY A 61 VAL A 68 -1 O TYR A 63 N ARG A 55
SHEET 3 B 4 LYS A 123 SER A 134 -1 O SER A 134 N THR A 67
SHEET 4 B 4 ARG A 109 PRO A 118 -1 N VAL A 117 O TRP A 124
SHEET 1 C 5 GLY A 220 ILE A 224 0
SHEET 2 C 5 PHE A 198 LEU A 202 -1 N GLN A 201 O SER A 221
SHEET 3 C 5 PHE A 389 ASP A 394 -1 O PHE A 393 N PHE A 198
SHEET 4 C 5 ARG A 399 SER A 405 -1 O ALA A 403 N TYR A 390
SHEET 5 C 5 TYR A 232 PRO A 240 -1 N THR A 239 O ILE A 400
SHEET 1 D 5 GLN A 259 ASP A 260 0
SHEET 2 D 5 ILE A 251 ILE A 256 -1 N ILE A 256 O GLN A 259
SHEET 3 D 5 ILE A 331 MET A 336 -1 O TYR A 334 N ARG A 253
SHEET 4 D 5 GLN A 342 ILE A 348 -1 O ILE A 348 N ILE A 331
SHEET 5 D 5 ALA A 417 VAL A 423 -1 O ALA A 417 N THR A 347
SHEET 1 E 4 SER A 273 VAL A 275 0
SHEET 2 E 4 THR A 379 MET A 381 1 O MET A 381 N ILE A 274
SHEET 3 E 4 LEU A 282 PRO A 285 -1 N ARG A 283 O VAL A 380
SHEET 4 E 4 ILE A 372 SER A 375 1 O SER A 373 N LEU A 282
SHEET 1 F 3 VAL A 316 TRP A 318 0
SHEET 2 F 3 ASP A 366 PHE A 370 -1 O ASP A 366 N TRP A 318
SHEET 3 F 3 LEU A 354 VAL A 357 -1 N ARG A 355 O LYS A 369
SHEET 1 G 8 LEU B 54 LYS B 57 0
SHEET 2 G 8 GLY B 61 VAL B 68 -1 O TYR B 63 N ARG B 55
SHEET 3 G 8 GLN B 73 ASP B 80 -1 O LEU B 75 N MET B 66
SHEET 4 G 8 GLY B 165 GLY B 168 1 O GLY B 165 N LEU B 78
SHEET 5 G 8 PHE B 86 GLY B 89 -1 N ALA B 87 O ILE B 166
SHEET 6 G 8 THR B 142 ASP B 154 1 O ILE B 150 N VAL B 88
SHEET 7 G 8 LYS B 123 SER B 134 -1 N LYS B 123 O ASP B 154
SHEET 8 G 8 ARG B 109 PRO B 118 -1 N LYS B 113 O LEU B 128
SHEET 1 H 4 LEU B 54 LYS B 57 0
SHEET 2 H 4 GLY B 61 VAL B 68 -1 O TYR B 63 N ARG B 55
SHEET 3 H 4 LYS B 123 SER B 134 -1 O SER B 134 N THR B 67
SHEET 4 H 4 ARG B 109 PRO B 118 -1 N LYS B 113 O LEU B 128
SHEET 1 I 5 GLY B 220 ILE B 224 0
SHEET 2 I 5 PHE B 198 LEU B 202 -1 N GLN B 201 O SER B 221
SHEET 3 I 5 PHE B 389 ASP B 394 -1 O PHE B 393 N PHE B 198
SHEET 4 I 5 ARG B 399 SER B 405 -1 O ALA B 403 N TYR B 390
SHEET 5 I 5 TYR B 232 PRO B 240 -1 N THR B 239 O ILE B 400
SHEET 1 J 5 GLN B 259 ASP B 260 0
SHEET 2 J 5 ILE B 251 ILE B 256 -1 N ILE B 256 O GLN B 259
SHEET 3 J 5 ILE B 331 MET B 336 -1 O TYR B 334 N ARG B 253
SHEET 4 J 5 GLN B 342 ILE B 348 -1 O ILE B 348 N ILE B 331
SHEET 5 J 5 ALA B 417 VAL B 423 -1 O ALA B 417 N THR B 347
SHEET 1 K 4 SER B 273 VAL B 275 0
SHEET 2 K 4 THR B 379 MET B 381 1 O MET B 381 N ILE B 274
SHEET 3 K 4 LEU B 282 PRO B 285 -1 N ARG B 283 O VAL B 380
SHEET 4 K 4 ILE B 372 SER B 375 1 O SER B 375 N LEU B 284
SHEET 1 L 3 VAL B 316 TRP B 318 0
SHEET 2 L 3 ASP B 366 PHE B 370 -1 O ASP B 366 N TRP B 318
SHEET 3 L 3 LEU B 354 VAL B 357 -1 N ARG B 355 O LYS B 369
SHEET 1 M 8 LEU D 54 LYS D 57 0
SHEET 2 M 8 GLY D 61 VAL D 68 -1 O TYR D 63 N ARG D 55
SHEET 3 M 8 GLN D 73 ASP D 80 -1 O VAL D 79 N TYR D 62
SHEET 4 M 8 GLY D 165 GLY D 168 1 O GLY D 165 N LEU D 78
SHEET 5 M 8 PHE D 86 GLY D 89 -1 N ALA D 87 O ILE D 166
SHEET 6 M 8 VAL D 143 ASP D 154 1 O ILE D 150 N VAL D 88
SHEET 7 M 8 GLY D 122 SER D 134 -1 N GLY D 129 O ILE D 147
SHEET 8 M 8 ARG D 109 TYR D 119 -1 N LYS D 113 O LEU D 128
SHEET 1 N 4 LEU D 54 LYS D 57 0
SHEET 2 N 4 GLY D 61 VAL D 68 -1 O TYR D 63 N ARG D 55
SHEET 3 N 4 GLY D 122 SER D 134 -1 O SER D 134 N THR D 67
SHEET 4 N 4 ARG D 109 TYR D 119 -1 N LYS D 113 O LEU D 128
SHEET 1 O 5 GLY D 220 ILE D 224 0
SHEET 2 O 5 PHE D 198 LEU D 202 -1 N GLN D 201 O SER D 221
SHEET 3 O 5 PHE D 389 ASP D 394 -1 O VAL D 391 N LEU D 200
SHEET 4 O 5 ARG D 399 SER D 405 -1 O GLY D 401 N VAL D 392
SHEET 5 O 5 TYR D 232 PRO D 240 -1 N THR D 239 O ILE D 400
SHEET 1 P 5 GLU D 248 VAL D 249 0
SHEET 2 P 5 SER D 273 VAL D 275 -1 O SER D 273 N VAL D 249
SHEET 3 P 5 THR D 379 MET D 381 1 O THR D 379 N ILE D 274
SHEET 4 P 5 LEU D 282 PRO D 285 -1 N ARG D 283 O VAL D 380
SHEET 5 P 5 ILE D 372 SER D 375 1 O SER D 375 N LEU D 284
SHEET 1 Q 5 GLN D 259 ASP D 260 0
SHEET 2 Q 5 ILE D 251 ILE D 256 -1 N ILE D 256 O GLN D 259
SHEET 3 Q 5 ILE D 331 MET D 336 -1 O TYR D 334 N VAL D 252
SHEET 4 Q 5 GLN D 342 ILE D 348 -1 O ILE D 348 N ILE D 331
SHEET 5 Q 5 ALA D 417 VAL D 423 -1 O GLU D 419 N ARG D 345
SHEET 1 R 3 VAL D 316 TRP D 318 0
SHEET 2 R 3 ASP D 366 PHE D 370 -1 O ASP D 366 N TRP D 318
SHEET 3 R 3 LEU D 354 VAL D 357 -1 N ARG D 355 O LYS D 369
SHEET 1 S 8 LEU E 54 LYS E 57 0
SHEET 2 S 8 GLY E 61 VAL E 68 -1 O TYR E 63 N ARG E 55
SHEET 3 S 8 GLN E 73 ASP E 80 -1 O LEU E 75 N MET E 66
SHEET 4 S 8 GLY E 165 GLY E 168 1 O LEU E 167 N LEU E 78
SHEET 5 S 8 PHE E 86 GLY E 89 -1 N ALA E 87 O ILE E 166
SHEET 6 S 8 VAL E 143 ASP E 154 1 O ILE E 150 N VAL E 88
SHEET 7 S 8 LYS E 123 SER E 134 -1 N GLU E 125 O GLU E 152
SHEET 8 S 8 ARG E 109 PRO E 118 -1 N VAL E 115 O GLY E 126
SHEET 1 T 4 LEU E 54 LYS E 57 0
SHEET 2 T 4 GLY E 61 VAL E 68 -1 O TYR E 63 N ARG E 55
SHEET 3 T 4 LYS E 123 SER E 134 -1 O SER E 134 N THR E 67
SHEET 4 T 4 ARG E 109 PRO E 118 -1 N VAL E 115 O GLY E 126
SHEET 1 U 5 GLY E 220 ILE E 224 0
SHEET 2 U 5 PHE E 198 LEU E 202 -1 N GLN E 201 O SER E 221
SHEET 3 U 5 PHE E 389 ASP E 394 -1 O VAL E 391 N LEU E 200
SHEET 4 U 5 ARG E 399 SER E 405 -1 O GLY E 401 N VAL E 392
SHEET 5 U 5 TYR E 232 PRO E 240 -1 N THR E 239 O ILE E 400
SHEET 1 V 5 GLN E 259 ASP E 260 0
SHEET 2 V 5 ILE E 251 ILE E 256 -1 N ILE E 256 O GLN E 259
SHEET 3 V 5 ILE E 331 MET E 336 -1 O TYR E 334 N ARG E 253
SHEET 4 V 5 GLN E 342 ILE E 348 -1 O ILE E 348 N ILE E 331
SHEET 5 V 5 ALA E 417 VAL E 423 -1 O GLU E 419 N ARG E 345
SHEET 1 W 4 SER E 273 VAL E 275 0
SHEET 2 W 4 THR E 379 MET E 381 1 O MET E 381 N ILE E 274
SHEET 3 W 4 LEU E 282 PRO E 285 -1 N ARG E 283 O VAL E 380
SHEET 4 W 4 ILE E 372 SER E 375 1 O SER E 375 N LEU E 284
SHEET 1 X 3 VAL E 316 TRP E 318 0
SHEET 2 X 3 ASP E 366 PHE E 370 -1 O ASP E 366 N TRP E 318
SHEET 3 X 3 LEU E 354 VAL E 357 -1 N ARG E 355 O LYS E 369
SSBOND 1 CYS A 203 CYS A 407 1555 1555 2.04
SSBOND 2 CYS A 265 CYS A 430 1555 1555 2.02
SSBOND 3 CYS A 317 CYS A 367 1555 1555 2.02
SSBOND 4 CYS B 203 CYS B 407 1555 1555 2.04
SSBOND 5 CYS B 265 CYS B 430 1555 1555 2.03
SSBOND 6 CYS B 317 CYS B 367 1555 1555 2.03
SSBOND 7 CYS D 203 CYS D 407 1555 1555 2.03
SSBOND 8 CYS D 265 CYS D 430 1555 1555 2.57
SSBOND 9 CYS D 317 CYS D 367 1555 1555 2.03
SSBOND 10 CYS E 203 CYS E 407 1555 1555 2.04
SSBOND 11 CYS E 265 CYS E 430 1555 1555 2.03
SSBOND 12 CYS E 317 CYS E 367 1555 1555 2.02
CISPEP 1 SER A 70 PRO A 71 0 -4.50
CISPEP 2 ARG A 176 PRO A 177 0 3.20
CISPEP 3 TYR A 270 ASP A 271 0 4.60
CISPEP 4 GLY A 420 PRO A 421 0 -0.26
CISPEP 5 SER B 70 PRO B 71 0 -1.38
CISPEP 6 ARG B 176 PRO B 177 0 5.79
CISPEP 7 TYR B 270 ASP B 271 0 -5.60
CISPEP 8 GLY B 420 PRO B 421 0 3.51
CISPEP 9 SER D 70 PRO D 71 0 -4.69
CISPEP 10 ARG D 176 PRO D 177 0 2.00
CISPEP 11 TYR D 270 ASP D 271 0 1.76
CISPEP 12 GLY D 420 PRO D 421 0 1.39
CISPEP 13 SER E 70 PRO E 71 0 -0.33
CISPEP 14 ARG E 176 PRO E 177 0 0.41
CISPEP 15 TYR E 270 ASP E 271 0 3.90
CISPEP 16 GLY E 420 PRO E 421 0 -1.53
SITE 1 AC1 18 LEU A 78 ASP A 80 GLY A 82 TYR A 119
SITE 2 AC1 18 GLN A 121 GLY A 122 LYS A 155 PHE A 156
SITE 3 AC1 18 ILE A 158 TYR A 246 ILE A 274 ASP A 276
SITE 4 AC1 18 GLY A 278 THR A 279 ARG A 283 THR A 377
SITE 5 AC1 18 VAL A 380 IOD A 502
SITE 1 AC2 4 THR A 279 ASN A 281 ARG A 283 0VB A 501
SITE 1 AC3 2 TYR A 116 PRO A 177
SITE 1 AC4 18 ASP B 80 GLY B 82 SER B 83 TYR B 119
SITE 2 AC4 18 GLN B 121 GLY B 122 LYS B 155 PHE B 156
SITE 3 AC4 18 ILE B 158 TRP B 163 TYR B 246 ILE B 274
SITE 4 AC4 18 ASP B 276 THR B 279 ARG B 283 THR B 377
SITE 5 AC4 18 VAL B 380 HOH B 722
SITE 1 AC5 2 ASN B 281 ARG B 283
SITE 1 AC6 2 TYR B 116 PRO B 177
SITE 1 AC7 17 LEU D 78 ASP D 80 TYR D 119 THR D 120
SITE 2 AC7 17 GLN D 121 LYS D 155 PHE D 156 ILE D 158
SITE 3 AC7 17 TRP D 163 TYR D 246 ILE D 274 ASP D 276
SITE 4 AC7 17 GLY D 278 THR D 279 ARG D 283 THR D 377
SITE 5 AC7 17 VAL D 380
SITE 1 AC8 2 ASN D 281 ARG D 283
SITE 1 AC9 2 TYR D 116 PRO D 177
SITE 1 BC1 17 LEU E 78 ASP E 80 GLY E 82 TYR E 119
SITE 2 BC1 17 GLN E 121 LYS E 155 PHE E 156 ILE E 158
SITE 3 BC1 17 TRP E 163 TYR E 246 ILE E 274 ASP E 276
SITE 4 BC1 17 GLY E 278 THR E 279 ARG E 283 THR E 377
SITE 5 BC1 17 VAL E 380
SITE 1 BC2 2 ASN E 281 ARG E 283
SITE 1 BC3 2 TYR E 116 PRO E 177
SITE 1 BC4 1 LYS E 123
CRYST1 86.540 131.177 90.315 90.00 97.61 90.00 P 1 21 1 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 0.011555 0.000000 0.001544 0.00000
SCALE2 0.000000 0.007623 0.000000 0.00000
SCALE3 0.000000 0.000000 0.011171 0.00000
(ATOM LINES ARE NOT SHOWN.)
END