HEADER HYDROLASE 01-SEP-09 3IVH
TITLE DESIGN AND SYNTHESIS OF POTENT BACE-1 INHIBITORS WITH CELLULAR
TITLE 2 ACTIVITY: STRUCTURE-ACTIVITY RELATIONSHIP OF P1 SUBSTITUENTS
COMPND MOL_ID: 1;
COMPND 2 MOLECULE: BETA-SECRETASE 1;
COMPND 3 CHAIN: A;
COMPND 4 SYNONYM: BETA-SITE AMYLOID PRECURSOR PROTEIN CLEAVING ENZYME 1, BETA-
COMPND 5 SITE APP CLEAVING ENZYME 1, MEMBRANE-ASSOCIATED ASPARTIC PROTEASE 2,
COMPND 6 MEMAPSIN-2, ASPARTYL PROTEASE 2, ASP 2, ASP2;
COMPND 7 EC: 3.4.23.46;
COMPND 8 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;
SOURCE 8 EXPRESSION_SYSTEM_VECTOR_TYPE: PLASMID;
SOURCE 9 EXPRESSION_SYSTEM_PLASMID: PQE70
KEYWDS ASPARTYL PROTEASE, BACE-1 INHIBITORS, ALZHEIMER'S DISEASE, STRUCTURE-
KEYWDS 2 BASED DRUG DESIGN, DISULFIDE BOND, GLYCOPROTEIN, HYDROLASE,
KEYWDS 3 MEMBRANE, PROTEASE, TRANSMEMBRANE, ZYMOGEN
EXPDTA X-RAY DIFFRACTION
AUTHOR H.PAN
REVDAT 2 13-JUL-11 3IVH 1 VERSN
REVDAT 1 05-JAN-10 3IVH 0
JRNL AUTH J.M.SEALY,A.P.TRUONG,L.TSO,G.D.PROBST,J.AQUINO,R.K.HOM,
JRNL AUTH 2 B.M.JAGODZINSKA,D.DRESSEN,D.W.WONE,L.BROGLEY,V.JOHN,
JRNL AUTH 3 J.S.TUNG,M.A.PLEISS,J.A.TUCKER,A.W.KONRADI,M.S.DAPPEN,
JRNL AUTH 4 G.TOTH,H.PAN,L.RUSLIM,J.MILLER,M.P.BOVA,S.SINHA,K.P.QUINN,
JRNL AUTH 5 J.M.SAUER
JRNL TITL DESIGN AND SYNTHESIS OF CELL POTENT BACE-1 INHIBITORS:
JRNL TITL 2 STRUCTURE-ACTIVITY RELATIONSHIP OF P1' SUBSTITUENTS.
JRNL REF BIOORG.MED.CHEM.LETT. V. 19 6386 2009
JRNL REFN ISSN 0960-894X
JRNL PMID 19811916
JRNL DOI 10.1016/J.BMCL.2009.09.061
REMARK 2
REMARK 2 RESOLUTION. 1.80 ANGSTROMS.
REMARK 3
REMARK 3 REFINEMENT.
REMARK 3 PROGRAM : REFMAC 5.1.25
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) : 1.80
REMARK 3 RESOLUTION RANGE LOW (ANGSTROMS) : NULL
REMARK 3 DATA CUTOFF (SIGMA(F)) : 0.000
REMARK 3 COMPLETENESS FOR RANGE (%) : 92.8
REMARK 3 NUMBER OF REFLECTIONS : 30386
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) : 0.208
REMARK 3 R VALUE (WORKING SET) : 0.206
REMARK 3 FREE R VALUE : 0.249
REMARK 3 FREE R VALUE TEST SET SIZE (%) : 5.000
REMARK 3 FREE R VALUE TEST SET COUNT : 1596
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) : 1.80
REMARK 3 BIN RESOLUTION RANGE LOW (A) : 1.85
REMARK 3 REFLECTION IN BIN (WORKING SET) : 2323
REMARK 3 BIN COMPLETENESS (WORKING+TEST) (%) : NULL
REMARK 3 BIN R VALUE (WORKING SET) : 0.2660
REMARK 3 BIN FREE R VALUE SET COUNT : 127
REMARK 3 BIN FREE R VALUE : 0.3040
REMARK 3
REMARK 3 NUMBER OF NON-HYDROGEN ATOMS USED IN REFINEMENT.
REMARK 3 PROTEIN ATOMS : 2980
REMARK 3 NUCLEIC ACID ATOMS : 0
REMARK 3 HETEROGEN ATOMS : 34
REMARK 3 SOLVENT ATOMS : 249
REMARK 3
REMARK 3 B VALUES.
REMARK 3 B VALUE TYPE : LIKELY RESIDUAL
REMARK 3 FROM WILSON PLOT (A**2) : NULL
REMARK 3 MEAN B VALUE (OVERALL, A**2) : 23.80
REMARK 3 OVERALL ANISOTROPIC B VALUE.
REMARK 3 B11 (A**2) : -1.95000
REMARK 3 B22 (A**2) : 0.61000
REMARK 3 B33 (A**2) : 1.24000
REMARK 3 B12 (A**2) : 0.00000
REMARK 3 B13 (A**2) : -0.54000
REMARK 3 B23 (A**2) : 0.00000
REMARK 3
REMARK 3 ESTIMATED OVERALL COORDINATE ERROR.
REMARK 3 ESU BASED ON R VALUE (A): 0.168
REMARK 3 ESU BASED ON FREE R VALUE (A): 0.153
REMARK 3 ESU BASED ON MAXIMUM LIKELIHOOD (A): 0.128
REMARK 3 ESU FOR B VALUES BASED ON MAXIMUM LIKELIHOOD (A**2): 4.419
REMARK 3
REMARK 3 CORRELATION COEFFICIENTS.
REMARK 3 CORRELATION COEFFICIENT FO-FC : 0.950
REMARK 3 CORRELATION COEFFICIENT FO-FC FREE : 0.926
REMARK 3
REMARK 3 RMS DEVIATIONS FROM IDEAL VALUES COUNT RMS WEIGHT
REMARK 3 BOND LENGTHS REFINED ATOMS (A): NULL ; NULL ; NULL
REMARK 3 BOND LENGTHS OTHERS (A): NULL ; NULL ; NULL
REMARK 3 BOND ANGLES REFINED ATOMS (DEGREES): NULL ; NULL ; NULL
REMARK 3 BOND ANGLES OTHERS (DEGREES): NULL ; NULL ; NULL
REMARK 3 TORSION ANGLES, PERIOD 1 (DEGREES): NULL ; NULL ; NULL
REMARK 3 TORSION ANGLES, PERIOD 2 (DEGREES): NULL ; NULL ; NULL
REMARK 3 TORSION ANGLES, PERIOD 3 (DEGREES): NULL ; NULL ; NULL
REMARK 3 TORSION ANGLES, PERIOD 4 (DEGREES): NULL ; NULL ; NULL
REMARK 3 CHIRAL-CENTER RESTRAINTS (A**3): NULL ; NULL ; NULL
REMARK 3 GENERAL PLANES REFINED ATOMS (A): NULL ; NULL ; NULL
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 SIDE-CHAIN BOND REFINED ATOMS (A**2): NULL ; NULL ; NULL
REMARK 3 SIDE-CHAIN ANGLE REFINED 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 59 A 219
REMARK 3 RESIDUE RANGE : A 224 A 372
REMARK 3 RESIDUE RANGE : A 379 A 447
REMARK 3 ORIGIN FOR THE GROUP (A): 15.8990 -0.1960 10.1320
REMARK 3 T TENSOR
REMARK 3 T11: 0.0773 T22: 0.0775
REMARK 3 T33: 0.0042 T12: 0.0090
REMARK 3 T13: 0.0180 T23: 0.0008
REMARK 3 L TENSOR
REMARK 3 L11: 2.0064 L22: 1.3624
REMARK 3 L33: 0.2533 L12: 1.1264
REMARK 3 L13: 0.5428 L23: 0.5030
REMARK 3 S TENSOR
REMARK 3 S11: 0.0894 S12: 0.0401 S13: -0.0534
REMARK 3 S21: 0.1492 S22: -0.0437 S23: 0.0165
REMARK 3 S31: 0.0244 S32: -0.0214 S33: -0.0458
REMARK 3
REMARK 3 BULK SOLVENT MODELLING.
REMARK 3 METHOD USED : BABINET MODEL WITH MASK
REMARK 3 PARAMETERS FOR MASK CALCULATION
REMARK 3 VDW PROBE RADIUS : 1.40
REMARK 3 ION PROBE RADIUS : 0.80
REMARK 3 SHRINKAGE RADIUS : 0.80
REMARK 3
REMARK 3 OTHER REFINEMENT REMARKS: HYDROGENS HAVE BEEN ADDED IN THE RIDING
REMARK 3 POSITIONS
REMARK 4
REMARK 4 3IVH COMPLIES WITH FORMAT V. 3.30, 13-JUL-11
REMARK 100
REMARK 100 THIS ENTRY HAS BEEN PROCESSED BY RCSB ON 22-SEP-09.
REMARK 100 THE RCSB ID CODE IS RCSB054915.
REMARK 200
REMARK 200 EXPERIMENTAL DETAILS
REMARK 200 EXPERIMENT TYPE : X-RAY DIFFRACTION
REMARK 200 DATE OF DATA COLLECTION : 13-SEP-04
REMARK 200 TEMPERATURE (KELVIN) : NULL
REMARK 200 PH : 4.5
REMARK 200 NUMBER OF CRYSTALS USED : 1
REMARK 200
REMARK 200 SYNCHROTRON (Y/N) : Y
REMARK 200 RADIATION SOURCE : ALS
REMARK 200 BEAMLINE : 8.3.1
REMARK 200 X-RAY GENERATOR MODEL : NULL
REMARK 200 MONOCHROMATIC OR LAUE (M/L) : M
REMARK 200 WAVELENGTH OR RANGE (A) : 1.11587
REMARK 200 MONOCHROMATOR : NULL
REMARK 200 OPTICS : NULL
REMARK 200
REMARK 200 DETECTOR TYPE : CCD
REMARK 200 DETECTOR MANUFACTURER : ADSC QUANTUM 315R
REMARK 200 INTENSITY-INTEGRATION SOFTWARE : MOSFLM
REMARK 200 DATA SCALING SOFTWARE : SCALA
REMARK 200
REMARK 200 NUMBER OF UNIQUE REFLECTIONS : 30386
REMARK 200 RESOLUTION RANGE HIGH (A) : 1.800
REMARK 200 RESOLUTION RANGE LOW (A) : NULL
REMARK 200 REJECTION CRITERIA (SIGMA(I)) : NULL
REMARK 200
REMARK 200 OVERALL.
REMARK 200 COMPLETENESS FOR RANGE (%) : NULL
REMARK 200 DATA REDUNDANCY : NULL
REMARK 200 R MERGE (I) : NULL
REMARK 200 R SYM (I) : NULL
REMARK 200 <I/SIGMA(I)> FOR THE DATA SET : NULL
REMARK 200
REMARK 200 IN THE HIGHEST RESOLUTION SHELL.
REMARK 200 HIGHEST RESOLUTION SHELL, RANGE HIGH (A) : 1.80
REMARK 200 HIGHEST RESOLUTION SHELL, RANGE LOW (A) : 1.85
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: MOLECULAR REPLACEMENT
REMARK 200 SOFTWARE USED: AMORE
REMARK 200 STARTING MODEL: NULL
REMARK 200
REMARK 200 REMARK: NULL
REMARK 280
REMARK 280 CRYSTAL
REMARK 280 SOLVENT CONTENT, VS (%): 42.63
REMARK 280 MATTHEWS COEFFICIENT, VM (ANGSTROMS**3/DA): 2.14
REMARK 280
REMARK 280 CRYSTALLIZATION CONDITIONS: 0.1 M SODIUM ACETATE PH 4.5, 20%
REMARK 280 PEG200 COMPOUND WAS ADDED TO GIVE A FINAL MOLAR ACCESS OF
REMARK 280 COMPOUND:PROTEIN OF 2.5:1, VAPOR DIFFUSION, SITTING DROP,
REMARK 280 TEMPERATURE 289K
REMARK 290
REMARK 290 CRYSTALLOGRAPHIC SYMMETRY
REMARK 290 SYMMETRY OPERATORS FOR SPACE GROUP: C 1 2 1
REMARK 290
REMARK 290 SYMOP SYMMETRY
REMARK 290 NNNMMM OPERATOR
REMARK 290 1555 X,Y,Z
REMARK 290 2555 -X,Y,-Z
REMARK 290 3555 X+1/2,Y+1/2,Z
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 0.00000
REMARK 290 SMTRY2 2 0.000000 1.000000 0.000000 0.00000
REMARK 290 SMTRY3 2 0.000000 0.000000 -1.000000 0.00000
REMARK 290 SMTRY1 3 1.000000 0.000000 0.000000 36.46200
REMARK 290 SMTRY2 3 0.000000 1.000000 0.000000 52.59050
REMARK 290 SMTRY3 3 0.000000 0.000000 1.000000 0.00000
REMARK 290 SMTRY1 4 -1.000000 0.000000 0.000000 36.46200
REMARK 290 SMTRY2 4 0.000000 1.000000 0.000000 52.59050
REMARK 290 SMTRY3 4 0.000000 0.000000 -1.000000 0.00000
REMARK 290
REMARK 290 REMARK: NULL
REMARK 300
REMARK 300 BIOMOLECULE: 1
REMARK 300 SEE REMARK 350 FOR THE AUTHOR PROVIDED AND/OR PROGRAM
REMARK 300 GENERATED ASSEMBLY INFORMATION FOR THE STRUCTURE IN
REMARK 300 THIS ENTRY. THE REMARK MAY ALSO PROVIDE INFORMATION ON
REMARK 300 BURIED SURFACE AREA.
REMARK 350
REMARK 350 COORDINATES FOR A COMPLETE MULTIMER REPRESENTING THE KNOWN
REMARK 350 BIOLOGICALLY SIGNIFICANT OLIGOMERIZATION STATE OF THE
REMARK 350 MOLECULE CAN BE GENERATED BY APPLYING BIOMT TRANSFORMATIONS
REMARK 350 GIVEN BELOW. BOTH NON-CRYSTALLOGRAPHIC AND
REMARK 350 CRYSTALLOGRAPHIC OPERATIONS ARE GIVEN.
REMARK 350
REMARK 350 BIOMOLECULE: 1
REMARK 350 AUTHOR DETERMINED BIOLOGICAL UNIT: MONOMERIC
REMARK 350 SOFTWARE DETERMINED QUATERNARY STRUCTURE: MONOMERIC
REMARK 350 SOFTWARE USED: 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 MET A 56
REMARK 465 ARG A 57
REMARK 465 GLY A 58
REMARK 465 PHE A 220
REMARK 465 PRO A 221
REMARK 465 LEU A 222
REMARK 465 ASN A 223
REMARK 465 VAL A 373
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 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 ARG A 454
REMARK 465 SER A 455
REMARK 465 HIS A 456
REMARK 465 HIS A 457
REMARK 465 HIS A 458
REMARK 465 HIS A 459
REMARK 465 HIS A 460
REMARK 465 HIS A 461
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 A 442 CB - CG - OD2 ANGL. DEV. = 5.5 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 PHE A 60 133.98 -178.04
REMARK 500 TYR A 132 -159.56 -95.96
REMARK 500 PHE A 169 -62.35 -97.85
REMARK 500 SER A 225 -111.88 64.12
REMARK 500 TRP A 258 -74.38 -148.46
REMARK 500 ASP A 284 -89.40 84.65
REMARK 500 ASN A 354 -0.83 80.73
REMARK 500 ALA A 384 30.43 -95.09
REMARK 500 HIS A 423 -73.45 -55.67
REMARK 500 ASP A 424 151.84 67.51
REMARK 500 ASP A 439 127.37 84.06
REMARK 500 MET A 440 -31.08 -145.05
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 TYR A 283 ASP A 284 -145.72
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 1LI A 1
DBREF 3IVH A 57 453 UNP P56817 BACE1_HUMAN 57 453
SEQADV 3IVH MET A 56 UNP P56817 EXPRESSION TAG
SEQADV 3IVH ARG A 454 UNP P56817 EXPRESSION TAG
SEQADV 3IVH SER A 455 UNP P56817 EXPRESSION TAG
SEQADV 3IVH HIS A 456 UNP P56817 EXPRESSION TAG
SEQADV 3IVH HIS A 457 UNP P56817 EXPRESSION TAG
SEQADV 3IVH HIS A 458 UNP P56817 EXPRESSION TAG
SEQADV 3IVH HIS A 459 UNP P56817 EXPRESSION TAG
SEQADV 3IVH HIS A 460 UNP P56817 EXPRESSION TAG
SEQADV 3IVH HIS A 461 UNP P56817 EXPRESSION TAG
SEQRES 1 A 406 MET ARG GLY SER PHE VAL GLU MET VAL ASP ASN LEU ARG
SEQRES 2 A 406 GLY LYS SER GLY GLN GLY TYR TYR VAL GLU MET THR VAL
SEQRES 3 A 406 GLY SER PRO PRO GLN THR LEU ASN ILE LEU VAL ASP THR
SEQRES 4 A 406 GLY SER SER ASN PHE ALA VAL GLY ALA ALA PRO HIS PRO
SEQRES 5 A 406 PHE LEU HIS ARG TYR TYR GLN ARG GLN LEU SER SER THR
SEQRES 6 A 406 TYR ARG ASP LEU ARG LYS GLY VAL TYR VAL PRO TYR THR
SEQRES 7 A 406 GLN GLY LYS TRP GLU GLY GLU LEU GLY THR ASP LEU VAL
SEQRES 8 A 406 SER ILE PRO HIS GLY PRO ASN VAL THR VAL ARG ALA ASN
SEQRES 9 A 406 ILE ALA ALA ILE THR GLU SER ASP LYS PHE PHE ILE ASN
SEQRES 10 A 406 GLY SER ASN TRP GLU GLY ILE LEU GLY LEU ALA TYR ALA
SEQRES 11 A 406 GLU ILE ALA ARG PRO ASP ASP SER LEU GLU PRO PHE PHE
SEQRES 12 A 406 ASP SER LEU VAL LYS GLN THR HIS VAL PRO ASN LEU PHE
SEQRES 13 A 406 SER LEU GLN LEU CYS GLY ALA GLY PHE PRO LEU ASN GLN
SEQRES 14 A 406 SER GLU VAL LEU ALA SER VAL GLY GLY SER MET ILE ILE
SEQRES 15 A 406 GLY GLY ILE ASP HIS SER LEU TYR THR GLY SER LEU TRP
SEQRES 16 A 406 TYR THR PRO ILE ARG ARG GLU TRP TYR TYR GLU VAL ILE
SEQRES 17 A 406 ILE VAL ARG VAL GLU ILE ASN GLY GLN ASP LEU LYS MET
SEQRES 18 A 406 ASP CYS LYS GLU TYR ASN TYR ASP LYS SER ILE VAL ASP
SEQRES 19 A 406 SER GLY THR THR ASN LEU ARG LEU PRO LYS LYS VAL PHE
SEQRES 20 A 406 GLU ALA ALA VAL LYS SER ILE LYS ALA ALA SER SER THR
SEQRES 21 A 406 GLU LYS PHE PRO ASP GLY PHE TRP LEU GLY GLU GLN LEU
SEQRES 22 A 406 VAL CYS TRP GLN ALA GLY THR THR PRO TRP ASN ILE PHE
SEQRES 23 A 406 PRO VAL ILE SER LEU TYR LEU MET GLY GLU VAL THR ASN
SEQRES 24 A 406 GLN SER PHE ARG ILE THR ILE LEU PRO GLN GLN TYR LEU
SEQRES 25 A 406 ARG PRO VAL GLU ASP VAL ALA THR SER GLN ASP ASP CYS
SEQRES 26 A 406 TYR LYS PHE ALA ILE SER GLN SER SER THR GLY THR VAL
SEQRES 27 A 406 MET GLY ALA VAL ILE MET GLU GLY PHE TYR VAL VAL PHE
SEQRES 28 A 406 ASP ARG ALA ARG LYS ARG ILE GLY PHE ALA VAL SER ALA
SEQRES 29 A 406 CYS HIS VAL HIS ASP GLU PHE ARG THR ALA ALA VAL GLU
SEQRES 30 A 406 GLY PRO PHE VAL THR LEU ASP MET GLU ASP CYS GLY TYR
SEQRES 31 A 406 ASN ILE PRO GLN THR ASP GLU SER ARG SER HIS HIS HIS
SEQRES 32 A 406 HIS HIS HIS
HET 1LI A 1 34
HETNAM 1LI N-[(1S,2R)-3-{[1-(3-TERT-BUTYLPHENYL)CYCLOHEXYL]AMINO}-
HETNAM 2 1LI 1-(3,5-DIFLUOROBENZYL)-2-HYDROXYPROPYL]ACETAMIDE
FORMUL 2 1LI C28 H38 F2 N2 O2
FORMUL 3 HOH *249(H2 O)
HELIX 1 1 PHE A 60 VAL A 64 5 5
HELIX 2 2 GLN A 114 SER A 118 5 5
HELIX 3 3 TYR A 184 ALA A 188 5 5
HELIX 4 4 PRO A 196 THR A 205 1 10
HELIX 5 5 ASP A 241 SER A 243 5 3
HELIX 6 6 ASP A 277 TYR A 281 5 5
HELIX 7 7 LYS A 299 SER A 313 1 15
HELIX 8 8 PRO A 319 LEU A 324 1 6
HELIX 9 9 PRO A 337 PHE A 341 5 5
HELIX 10 10 LEU A 362 TYR A 366 1 5
HELIX 11 11 GLY A 395 GLU A 400 1 6
HELIX 12 12 MET A 440 GLY A 444 5 5
SHEET 1 A 9 ARG A 122 PRO A 131 0
SHEET 2 A 9 LYS A 136 SER A 147 -1 O GLY A 139 N VAL A 128
SHEET 3 A 9 TYR A 75 VAL A 81 -1 N THR A 80 O SER A 147
SHEET 4 A 9 LEU A 67 LYS A 70 -1 N ARG A 68 O TYR A 76
SHEET 5 A 9 SER A 230 ILE A 237 -1 O VAL A 231 N GLY A 69
SHEET 6 A 9 PHE A 211 LEU A 215 -1 N GLN A 214 O SER A 234
SHEET 7 A 9 PHE A 402 ASP A 407 -1 O PHE A 406 N PHE A 211
SHEET 8 A 9 ARG A 412 SER A 418 -1 O ALA A 416 N TYR A 403
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 GLY A 139 N VAL A 128
SHEET 3 B13 VAL A 156 ASP A 167 -1 O ILE A 160 N GLY A 142
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 75 VAL A 81 -1 N VAL A 77 O ILE A 90
SHEET 8 B13 LEU A 67 LYS A 70 -1 N ARG A 68 O TYR A 76
SHEET 9 B13 SER A 230 ILE A 237 -1 O VAL A 231 N GLY A 69
SHEET 10 B13 PHE A 211 LEU A 215 -1 N GLN A 214 O SER A 234
SHEET 11 B13 PHE A 402 ASP A 407 -1 O PHE A 406 N PHE A 211
SHEET 12 B13 ARG A 412 SER A 418 -1 O ALA A 416 N TYR A 403
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 361 N ILE A 344
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 VAL A 370 -1 N ARG A 368 O LYS A 382
SSBOND 1 CYS A 216 CYS A 420 1555 1555 2.18
SSBOND 2 CYS A 278 CYS A 443 1555 1555 2.20
SSBOND 3 CYS A 330 CYS A 380 1555 1555 2.51
CISPEP 1 SER A 83 PRO A 84 0 -0.27
CISPEP 2 ARG A 189 PRO A 190 0 0.15
CISPEP 3 GLY A 433 PRO A 434 0 -1.02
SITE 1 AC1 17 HOH A 11 LEU A 91 ASP A 93 GLY A 95
SITE 2 AC1 17 SER A 96 PRO A 131 TYR A 132 THR A 133
SITE 3 AC1 17 GLY A 135 PHE A 169 ILE A 171 TRP A 176
SITE 4 AC1 17 TYR A 259 ILE A 287 ASP A 289 GLY A 291
SITE 5 AC1 17 THR A 292
CRYST1 72.924 105.181 51.029 90.00 95.25 90.00 C 1 2 1 4
ORIGX1 1.000000 0.000000 0.000000 0.00000
ORIGX2 0.000000 1.000000 0.000000 0.00000
ORIGX3 0.000000 0.000000 1.000000 0.00000
SCALE1 0.013713 0.000000 0.001261 0.00000
SCALE2 0.000000 0.009507 0.000000 0.00000
SCALE3 0.000000 0.000000 0.019679 0.00000
(ATOM LINES ARE NOT SHOWN.)
END
