HEADER HYDROLASE/HYDROLASE INHIBITOR 15-JUN-12 4FM7
TITLE CRYSTAL STRUCTURE OF BACE WITH COMPOUND 14G
COMPND MOL_ID: 1;
COMPND 2 MOLECULE: BETA-SECRETASE 1;
COMPND 3 CHAIN: A;
COMPND 4 FRAGMENT: UNP RESIDUES 58-453;
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 ASPARTYL PROTEASE, HYDROLASE-HYDROLASE INHIBITOR COMPLEX
EXPDTA X-RAY DIFFRACTION
AUTHOR F.F.VAJDOS,A.H.VARGHESE
REVDAT 2 19-JUN-13 4FM7 1 JRNL
REVDAT 1 03-OCT-12 4FM7 0
JRNL AUTH M.A.BRODNEY,G.BARREIRO,K.OGILVIE,E.HAJOS-KORCSOK,J.MURRAY,
JRNL AUTH 2 F.VAJDOS,C.AMBROISE,C.CHRISTOFFERSEN,K.FISHER,L.LANYON,
JRNL AUTH 3 J.LIU,C.E.NOLAN,J.M.WITHKA,K.A.BORZILLERI,I.EFREMOV,
JRNL AUTH 4 C.E.OBORSKI,A.VARGHESE,B.T.O'NEILL
JRNL TITL SPIROCYCLIC SULFAMIDES AS BETA-SECRETASE 1 (BACE-1)
JRNL TITL 2 INHIBITORS FOR THE TREATMENT OF ALZHEIMER'S DISEASE:
JRNL TITL 3 UTILIZATION OF STRUCTURE BASED DRUG DESIGN, WATERMAP, AND
JRNL TITL 4 CNS PENETRATION STUDIES TO IDENTIFY CENTRALLY EFFICACIOUS
JRNL TITL 5 INHIBITORS.
JRNL REF J.MED.CHEM. V. 55 9224 2012
JRNL REFN ISSN 0022-2623
JRNL PMID 22984865
JRNL DOI 10.1021/JM3009426
REMARK 1
REMARK 1 REFERENCE 1
REMARK 1 AUTH A.G.TOMASSELLI,D.J.PADDOCK,T.L.EMMONS,A.M.MILDNER,J.W.LEONE,
REMARK 1 AUTH 2 J.M.LULL,J.I.CIALDELLA,D.B.PRINCE,H.D.FISCHER,
REMARK 1 AUTH 3 R.L.HEINRIKSON,T.E.BENSON
REMARK 1 TITL HIGH YIELD EXPRESSION OF HUMAN BACE CONSTRUCTS IN ESCHERICIA
REMARK 1 TITL 2 COLI FOR REFOLDING, PURIFICATION, AND HIGH RESOLUTION
REMARK 1 TITL 3 DIFFRACTING CRYSTAL FORMS.
REMARK 1 REF PROTEIN PEPT.LETT. V. 15 131 2008
REMARK 1 REFN ISSN 0929-8665
REMARK 1 PMID 18289105
REMARK 2
REMARK 2 RESOLUTION. 1.56 ANGSTROMS.
REMARK 3
REMARK 3 REFINEMENT.
REMARK 3 PROGRAM : BUSTER 2.11.2
REMARK 3 AUTHORS : BRICOGNE,BLANC,BRANDL,FLENSBURG,KELLER,
REMARK 3 : PACIOREK,ROVERSI,SHARFF,SMART,VONRHEIN,
REMARK 3 : WOMACK,MATTHEWS,TEN EYCK,TRONRUD
REMARK 3
REMARK 3 DATA USED IN REFINEMENT.
REMARK 3 RESOLUTION RANGE HIGH (ANGSTROMS) : 1.56
REMARK 3 RESOLUTION RANGE LOW (ANGSTROMS) : 51.88
REMARK 3 DATA CUTOFF (SIGMA(F)) : 0.000
REMARK 3 COMPLETENESS FOR RANGE (%) : 86.8
REMARK 3 NUMBER OF REFLECTIONS : 48404
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) : 0.229
REMARK 3 R VALUE (WORKING SET) : 0.227
REMARK 3 FREE R VALUE : 0.264
REMARK 3 FREE R VALUE TEST SET SIZE (%) : 5.080
REMARK 3 FREE R VALUE TEST SET COUNT : 2458
REMARK 3 ESTIMATED ERROR OF FREE R VALUE : NULL
REMARK 3
REMARK 3 FIT IN THE HIGHEST RESOLUTION BIN.
REMARK 3 TOTAL NUMBER OF BINS USED : 20
REMARK 3 BIN RESOLUTION RANGE HIGH (ANGSTROMS) : 1.56
REMARK 3 BIN RESOLUTION RANGE LOW (ANGSTROMS) : 1.60
REMARK 3 BIN COMPLETENESS (WORKING+TEST) (%) : 86.77
REMARK 3 REFLECTIONS IN BIN (WORKING + TEST SET) : 2059
REMARK 3 BIN R VALUE (WORKING + TEST SET) : 0.2475
REMARK 3 REFLECTIONS IN BIN (WORKING SET) : 1966
REMARK 3 BIN R VALUE (WORKING SET) : 0.2462
REMARK 3 BIN FREE R VALUE : 0.2754
REMARK 3 BIN FREE R VALUE TEST SET SIZE (%) : 4.52
REMARK 3 BIN FREE R VALUE TEST SET COUNT : 93
REMARK 3 ESTIMATED ERROR OF BIN FREE R VALUE : NULL
REMARK 3
REMARK 3 NUMBER OF NON-HYDROGEN ATOMS USED IN REFINEMENT.
REMARK 3 PROTEIN ATOMS : 3106
REMARK 3 NUCLEIC ACID ATOMS : 0
REMARK 3 HETEROGEN ATOMS : 35
REMARK 3 SOLVENT ATOMS : 461
REMARK 3
REMARK 3 B VALUES.
REMARK 3 FROM WILSON PLOT (A**2) : NULL
REMARK 3 MEAN B VALUE (OVERALL, A**2) : 21.99
REMARK 3 OVERALL ANISOTROPIC B VALUE.
REMARK 3 B11 (A**2) : 1.11210
REMARK 3 B22 (A**2) : 3.07740
REMARK 3 B33 (A**2) : -4.18960
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 COORDINATE ERROR.
REMARK 3 ESD FROM LUZZATI PLOT (A) : 0.28
REMARK 3 DPI (BLOW EQ-10) BASED ON R VALUE (A) : NULL
REMARK 3 DPI (BLOW EQ-9) BASED ON FREE R VALUE (A) : NULL
REMARK 3 DPI (CRUICKSHANK) BASED ON R VALUE (A) : 0.12
REMARK 3 DPI (CRUICKSHANK) BASED ON FREE R VALUE (A) : NULL
REMARK 3
REMARK 3 REFERENCES: BLOW, D. (2002) ACTA CRYST D58, 792-797
REMARK 3 CRUICKSHANK, D.W.J. (1999) ACTA CRYST D55, 583-601
REMARK 3
REMARK 3 CORRELATION COEFFICIENTS.
REMARK 3 CORRELATION COEFFICIENT FO-FC : 0.919
REMARK 3 CORRELATION COEFFICIENT FO-FC FREE : 0.875
REMARK 3
REMARK 3 NUMBER OF GEOMETRIC FUNCTION TERMS DEFINED : 15
REMARK 3 TERM COUNT WEIGHT FUNCTION.
REMARK 3 BOND LENGTHS : 3225 ; 2.000 ; HARMONIC
REMARK 3 BOND ANGLES : 4392 ; 2.000 ; HARMONIC
REMARK 3 TORSION ANGLES : 1066 ; 2.000 ; SINUSOIDAL
REMARK 3 TRIGONAL CARBON PLANES : 75 ; 2.000 ; HARMONIC
REMARK 3 GENERAL PLANES : 474 ; 5.000 ; HARMONIC
REMARK 3 ISOTROPIC THERMAL FACTORS : 3225 ; 20.000 ; HARMONIC
REMARK 3 BAD NON-BONDED CONTACTS : 0 ; 5.000 ; SEMIHARMONIC
REMARK 3 IMPROPER TORSIONS : NULL ; NULL ; NULL
REMARK 3 PSEUDOROTATION ANGLES : NULL ; NULL ; NULL
REMARK 3 CHIRAL IMPROPER TORSION : 410 ; 5.000 ; SEMIHARMONIC
REMARK 3 SUM OF OCCUPANCIES : NULL ; NULL ; NULL
REMARK 3 UTILITY DISTANCES : NULL ; NULL ; NULL
REMARK 3 UTILITY ANGLES : NULL ; NULL ; NULL
REMARK 3 UTILITY TORSION : NULL ; NULL ; NULL
REMARK 3 IDEAL-DIST CONTACT TERM : 4161 ; 4.000 ; SEMIHARMONIC
REMARK 3
REMARK 3 RMS DEVIATIONS FROM IDEAL VALUES.
REMARK 3 BOND LENGTHS (A) : 0.010
REMARK 3 BOND ANGLES (DEGREES) : 1.17
REMARK 3 PEPTIDE OMEGA TORSION ANGLES (DEGREES) : 3.98
REMARK 3 OTHER TORSION ANGLES (DEGREES) : 17.00
REMARK 3
REMARK 3 TLS DETAILS
REMARK 3 NUMBER OF TLS GROUPS : NULL
REMARK 3
REMARK 3 OTHER REFINEMENT REMARKS: NULL
REMARK 4
REMARK 4 4FM7 COMPLIES WITH FORMAT V. 3.30, 13-JUL-11
REMARK 100
REMARK 100 THIS ENTRY HAS BEEN PROCESSED BY RCSB ON 21-JUN-12.
REMARK 100 THE RCSB ID CODE IS RCSB073073.
REMARK 200
REMARK 200 EXPERIMENTAL DETAILS
REMARK 200 EXPERIMENT TYPE : X-RAY DIFFRACTION
REMARK 200 DATE OF DATA COLLECTION : 24-NOV-09
REMARK 200 TEMPERATURE (KELVIN) : 100
REMARK 200 PH : NULL
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 MICROMAX-007 HF
REMARK 200 MONOCHROMATIC OR LAUE (M/L) : M
REMARK 200 WAVELENGTH OR RANGE (A) : 1.5418
REMARK 200 MONOCHROMATOR : NULL
REMARK 200 OPTICS : NULL
REMARK 200
REMARK 200 DETECTOR TYPE : IMAGE PLATE
REMARK 200 DETECTOR MANUFACTURER : RIGAKU RAXIS IV++
REMARK 200 INTENSITY-INTEGRATION SOFTWARE : XSCALE
REMARK 200 DATA SCALING SOFTWARE : SCALA
REMARK 200
REMARK 200 NUMBER OF UNIQUE REFLECTIONS : 51711
REMARK 200 RESOLUTION RANGE HIGH (A) : 1.557
REMARK 200 RESOLUTION RANGE LOW (A) : 100.682
REMARK 200 REJECTION CRITERIA (SIGMA(I)) : NULL
REMARK 200
REMARK 200 OVERALL.
REMARK 200 COMPLETENESS FOR RANGE (%) : 92.3
REMARK 200 DATA REDUNDANCY : 4.000
REMARK 200 R MERGE (I) : NULL
REMARK 200 R SYM (I) : 0.03900
REMARK 200 <I/SIGMA(I)> FOR THE DATA SET : 18.3000
REMARK 200
REMARK 200 IN THE HIGHEST RESOLUTION SHELL.
REMARK 200 HIGHEST RESOLUTION SHELL, RANGE HIGH (A) : 1.56
REMARK 200 HIGHEST RESOLUTION SHELL, RANGE LOW (A) : 1.64
REMARK 200 COMPLETENESS FOR SHELL (%) : 60.8
REMARK 200 DATA REDUNDANCY IN SHELL : 1.80
REMARK 200 R MERGE FOR SHELL (I) : 0.30700
REMARK 200 R SYM FOR SHELL (I) : 0.30700
REMARK 200 <I/SIGMA(I)> FOR SHELL : 2.600
REMARK 200
REMARK 200 DIFFRACTION PROTOCOL: SINGLE WAVELENGTH
REMARK 200 METHOD USED TO DETERMINE THE STRUCTURE: FOURIER SYNTHESIS
REMARK 200 SOFTWARE USED: NULL
REMARK 200 STARTING MODEL: NULL
REMARK 200
REMARK 200 REMARK: NULL
REMARK 280
REMARK 280 CRYSTAL
REMARK 280 SOLVENT CONTENT, VS (%): 42.96
REMARK 280 MATTHEWS COEFFICIENT, VM (ANGSTROMS**3/DA): 2.16
REMARK 280
REMARK 280 CRYSTALLIZATION CONDITIONS: 30% PEG 200, 0.1 M SODIUM ACETATE, PH
REMARK 280 5.2-5.4; PROTEIN BUFFER IS NABORATE, PH 8.5, VAPOR DIFFUSION,
REMARK 280 TEMPERATURE 298K
REMARK 290
REMARK 290 CRYSTALLOGRAPHIC SYMMETRY
REMARK 290 SYMMETRY OPERATORS FOR SPACE GROUP: C 2 2 21
REMARK 290
REMARK 290 SYMOP SYMMETRY
REMARK 290 NNNMMM OPERATOR
REMARK 290 1555 X,Y,Z
REMARK 290 2555 -X,-Y,Z+1/2
REMARK 290 3555 -X,Y,-Z+1/2
REMARK 290 4555 X,-Y,-Z
REMARK 290 5555 X+1/2,Y+1/2,Z
REMARK 290 6555 -X+1/2,-Y+1/2,Z+1/2
REMARK 290 7555 -X+1/2,Y+1/2,-Z+1/2
REMARK 290 8555 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 50.34100
REMARK 290 SMTRY1 3 -1.000000 0.000000 0.000000 0.00000
REMARK 290 SMTRY2 3 0.000000 1.000000 0.000000 0.00000
REMARK 290 SMTRY3 3 0.000000 0.000000 -1.000000 50.34100
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 0.00000
REMARK 290 SMTRY1 5 1.000000 0.000000 0.000000 37.23550
REMARK 290 SMTRY2 5 0.000000 1.000000 0.000000 51.95250
REMARK 290 SMTRY3 5 0.000000 0.000000 1.000000 0.00000
REMARK 290 SMTRY1 6 -1.000000 0.000000 0.000000 37.23550
REMARK 290 SMTRY2 6 0.000000 -1.000000 0.000000 51.95250
REMARK 290 SMTRY3 6 0.000000 0.000000 1.000000 50.34100
REMARK 290 SMTRY1 7 -1.000000 0.000000 0.000000 37.23550
REMARK 290 SMTRY2 7 0.000000 1.000000 0.000000 51.95250
REMARK 290 SMTRY3 7 0.000000 0.000000 -1.000000 50.34100
REMARK 290 SMTRY1 8 1.000000 0.000000 0.000000 37.23550
REMARK 290 SMTRY2 8 0.000000 -1.000000 0.000000 51.95250
REMARK 290 SMTRY3 8 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 375
REMARK 375 SPECIAL POSITION
REMARK 375 THE FOLLOWING ATOMS ARE FOUND TO BE WITHIN 0.15 ANGSTROMS
REMARK 375 OF A SYMMETRY RELATED ATOM AND ARE ASSUMED TO BE ON SPECIAL
REMARK 375 POSITIONS.
REMARK 375
REMARK 375 ATOM RES CSSEQI
REMARK 375 HOH A1039 LIES ON A SPECIAL POSITION.
REMARK 375 HOH A 927 LIES ON A SPECIAL POSITION.
REMARK 375 HOH A1060 LIES ON A SPECIAL POSITION.
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 GLY A -3
REMARK 465 SER A -2
REMARK 465 GLY A 158
REMARK 465 PHE A 159
REMARK 465 PRO A 160
REMARK 465 LEU A 161
REMARK 465 ASN A 162
REMARK 465 GLN A 163
REMARK 465 HIS A 399
REMARK 465 HIS A 400
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 89 42.35 -98.43
REMARK 500 TRP A 197 -84.55 -144.29
REMARK 500 ALA A 272 112.45 -39.37
REMARK 500 ASN A 293 -2.56 75.73
REMARK 500 ASP A 378 28.24 49.88
REMARK 500
REMARK 500 REMARK: NULL
REMARK 500
REMARK 500 GEOMETRY AND STEREOCHEMISTRY
REMARK 500 SUBTOPIC: CHIRAL CENTERS
REMARK 500
REMARK 500 UNEXPECTED CONFIGURATION OF THE FOLLOWING CHIRAL
REMARK 500 CENTER(S) USING IMPROPER CA--C--CB--N CHIRALITY
REMARK 500 FOR AMINO ACIDS AND C1'--O4'--N1(N9)--C2' FOR
REMARK 500 NUCLEIC ACIDS OR EQUIVALENT ANGLE
REMARK 500 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,A1,6X,F5.1,6X,A1,10X,A1,3X,A16)
REMARK 500
REMARK 500 M RES CSSEQI IMPROPER EXPECTED FOUND DETAILS
REMARK 500 THR A 26 21.8 L L OUTSIDE RANGE
REMARK 500 TYR A 305 23.6 L L OUTSIDE RANGE
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 798 DISTANCE = 6.15 ANGSTROMS
REMARK 525 HOH A 834 DISTANCE = 6.98 ANGSTROMS
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 ZN A 503 ZN
REMARK 620 N RES CSSEQI ATOM
REMARK 620 1 HIS A 396 ND1
REMARK 620 2 HIS A 398 NE2 120.7
REMARK 620 N 1
REMARK 800
REMARK 800 SITE
REMARK 800 SITE_IDENTIFIER: AC1
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: BINDING SITE FOR RESIDUE 0UP A 501
REMARK 800
REMARK 800 SITE_IDENTIFIER: AC2
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: BINDING SITE FOR RESIDUE ZN A 502
REMARK 800
REMARK 800 SITE_IDENTIFIER: AC3
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: BINDING SITE FOR RESIDUE ZN A 503
DBREF 4FM7 A -3 392 UNP P56817 BACE1_HUMAN 58 453
SEQADV 4FM7 ARG A 393 UNP P56817 EXPRESSION TAG
SEQADV 4FM7 SER A 394 UNP P56817 EXPRESSION TAG
SEQADV 4FM7 HIS A 395 UNP P56817 EXPRESSION TAG
SEQADV 4FM7 HIS A 396 UNP P56817 EXPRESSION TAG
SEQADV 4FM7 HIS A 397 UNP P56817 EXPRESSION TAG
SEQADV 4FM7 HIS A 398 UNP P56817 EXPRESSION TAG
SEQADV 4FM7 HIS A 399 UNP P56817 EXPRESSION TAG
SEQADV 4FM7 HIS A 400 UNP P56817 EXPRESSION TAG
SEQRES 1 A 404 GLY SER PHE VAL GLU MET VAL ASP ASN LEU ARG GLY LYS
SEQRES 2 A 404 SER GLY GLN GLY TYR TYR VAL GLU MET THR VAL GLY SER
SEQRES 3 A 404 PRO PRO GLN THR LEU ASN ILE LEU VAL ASP THR GLY SER
SEQRES 4 A 404 SER ASN PHE ALA VAL GLY ALA ALA PRO HIS PRO PHE LEU
SEQRES 5 A 404 HIS ARG TYR TYR GLN ARG GLN LEU SER SER THR TYR ARG
SEQRES 6 A 404 ASP LEU ARG LYS GLY VAL TYR VAL PRO TYR THR GLN GLY
SEQRES 7 A 404 LYS TRP GLU GLY GLU LEU GLY THR ASP LEU VAL SER ILE
SEQRES 8 A 404 PRO HIS GLY PRO ASN VAL THR VAL ARG ALA ASN ILE ALA
SEQRES 9 A 404 ALA ILE THR GLU SER ASP LYS PHE PHE ILE ASN GLY SER
SEQRES 10 A 404 ASN TRP GLU GLY ILE LEU GLY LEU ALA TYR ALA GLU ILE
SEQRES 11 A 404 ALA ARG PRO ASP ASP SER LEU GLU PRO PHE PHE ASP SER
SEQRES 12 A 404 LEU VAL LYS GLN THR HIS VAL PRO ASN LEU PHE SER LEU
SEQRES 13 A 404 GLN LEU CYS GLY ALA GLY PHE PRO LEU ASN GLN SER GLU
SEQRES 14 A 404 VAL LEU ALA SER VAL GLY GLY SER MET ILE ILE GLY GLY
SEQRES 15 A 404 ILE ASP HIS SER LEU TYR THR GLY SER LEU TRP TYR THR
SEQRES 16 A 404 PRO ILE ARG ARG GLU TRP TYR TYR GLU VAL ILE ILE VAL
SEQRES 17 A 404 ARG VAL GLU ILE ASN GLY GLN ASP LEU LYS MET ASP CYS
SEQRES 18 A 404 LYS GLU TYR ASN TYR ASP LYS SER ILE VAL ASP SER GLY
SEQRES 19 A 404 THR THR ASN LEU ARG LEU PRO LYS LYS VAL PHE GLU ALA
SEQRES 20 A 404 ALA VAL LYS SER ILE LYS ALA ALA SER SER THR GLU LYS
SEQRES 21 A 404 PHE PRO ASP GLY PHE TRP LEU GLY GLU GLN LEU VAL CYS
SEQRES 22 A 404 TRP GLN ALA GLY THR THR PRO TRP ASN ILE PHE PRO VAL
SEQRES 23 A 404 ILE SER LEU TYR LEU MET GLY GLU VAL THR ASN GLN SER
SEQRES 24 A 404 PHE ARG ILE THR ILE LEU PRO GLN GLN TYR LEU ARG PRO
SEQRES 25 A 404 VAL GLU ASP VAL ALA THR SER GLN ASP ASP CYS TYR LYS
SEQRES 26 A 404 PHE ALA ILE SER GLN SER SER THR GLY THR VAL MET GLY
SEQRES 27 A 404 ALA VAL ILE MET GLU GLY PHE TYR VAL VAL PHE ASP ARG
SEQRES 28 A 404 ALA ARG LYS ARG ILE GLY PHE ALA VAL SER ALA CYS HIS
SEQRES 29 A 404 VAL HIS ASP GLU PHE ARG THR ALA ALA VAL GLU GLY PRO
SEQRES 30 A 404 PHE VAL THR LEU ASP MET GLU ASP CYS GLY TYR ASN ILE
SEQRES 31 A 404 PRO GLN THR ASP GLU SER ARG SER HIS HIS HIS HIS HIS
SEQRES 32 A 404 HIS
HET 0UP A 501 33
HET ZN A 502 1
HET ZN A 503 1
HETNAM 0UP 4-{[(5R,7S)-1-(3-FLUOROPHENYL)-3,7-DIMETHYL-2,2-
HETNAM 2 0UP DIOXIDO-2-THIA-1,3,8-TRIAZASPIRO[4.5]DEC-8-YL]METHYL}-
HETNAM 3 0UP 2-(PROPAN-2-YLOXY)PHENOL
HETNAM ZN ZINC ION
FORMUL 2 0UP C24 H32 F N3 O4 S
FORMUL 3 ZN 2(ZN 2+)
FORMUL 5 HOH *461(H2 O)
HELIX 1 1 PHE A -1 VAL A 3 5 5
HELIX 2 2 GLN A 53 SER A 57 5 5
HELIX 3 3 TYR A 123 ALA A 127 5 5
HELIX 4 4 PRO A 135 THR A 144 1 10
HELIX 5 5 ASP A 180 SER A 182 5 3
HELIX 6 6 ASP A 216 TYR A 222 5 7
HELIX 7 7 LYS A 238 SER A 252 1 15
HELIX 8 8 PRO A 258 LEU A 263 1 6
HELIX 9 9 PRO A 276 PHE A 280 5 5
HELIX 10 10 LEU A 301 TYR A 305 1 5
HELIX 11 11 GLY A 334 GLU A 339 1 6
HELIX 12 12 THR A 389 HIS A 395 1 7
SHEET 1 A 9 ARG A 61 PRO A 70 0
SHEET 2 A 9 LYS A 75 SER A 86 -1 O LEU A 80 N LYS A 65
SHEET 3 A 9 TYR A 15 VAL A 20 -1 N THR A 19 O SER A 86
SHEET 4 A 9 LEU A 6 LYS A 9 -1 N ARG A 7 O TYR A 15
SHEET 5 A 9 SER A 169 ILE A 176 -1 O VAL A 170 N GLY A 8
SHEET 6 A 9 PHE A 150 LEU A 154 -1 N SER A 151 O ILE A 175
SHEET 7 A 9 PHE A 341 ASP A 346 -1 O PHE A 345 N PHE A 150
SHEET 8 A 9 ARG A 351 SER A 357 -1 O GLY A 353 N VAL A 344
SHEET 9 A 9 TYR A 184 PRO A 192 -1 N THR A 191 O ILE A 352
SHEET 1 B13 ARG A 61 PRO A 70 0
SHEET 2 B13 LYS A 75 SER A 86 -1 O LEU A 80 N LYS A 65
SHEET 3 B13 VAL A 95 ASP A 106 -1 O ALA A 101 N GLU A 79
SHEET 4 B13 PHE A 38 GLY A 41 1 N VAL A 40 O ILE A 102
SHEET 5 B13 GLY A 117 GLY A 120 -1 O ILE A 118 N ALA A 39
SHEET 6 B13 GLN A 25 ASP A 32 1 N LEU A 30 O LEU A 119
SHEET 7 B13 TYR A 15 VAL A 20 -1 N VAL A 16 O ILE A 29
SHEET 8 B13 LEU A 6 LYS A 9 -1 N ARG A 7 O TYR A 15
SHEET 9 B13 SER A 169 ILE A 176 -1 O VAL A 170 N GLY A 8
SHEET 10 B13 PHE A 150 LEU A 154 -1 N SER A 151 O ILE A 175
SHEET 11 B13 PHE A 341 ASP A 346 -1 O PHE A 345 N PHE A 150
SHEET 12 B13 ARG A 351 SER A 357 -1 O GLY A 353 N VAL A 344
SHEET 13 B13 TYR A 184 PRO A 192 -1 N THR A 191 O ILE A 352
SHEET 1 C 5 GLN A 211 ASP A 212 0
SHEET 2 C 5 ILE A 203 ILE A 208 -1 N ILE A 208 O GLN A 211
SHEET 3 C 5 ILE A 283 MET A 288 -1 O TYR A 286 N ARG A 205
SHEET 4 C 5 GLN A 294 ILE A 300 -1 O ILE A 300 N ILE A 283
SHEET 5 C 5 ALA A 369 VAL A 375 -1 O ALA A 369 N THR A 299
SHEET 1 D 4 SER A 225 VAL A 227 0
SHEET 2 D 4 THR A 331 MET A 333 1 O MET A 333 N ILE A 226
SHEET 3 D 4 LEU A 234 PRO A 237 -1 N ARG A 235 O VAL A 332
SHEET 4 D 4 ILE A 324 SER A 327 1 O SER A 325 N LEU A 236
SHEET 1 E 3 VAL A 268 GLN A 271 0
SHEET 2 E 3 ASP A 317 PHE A 322 -1 O ASP A 318 N TRP A 270
SHEET 3 E 3 LEU A 306 PRO A 308 -1 N ARG A 307 O LYS A 321
SSBOND 1 CYS A 155 CYS A 359 1555 1555 2.04
SSBOND 2 CYS A 217 CYS A 382 1555 1555 2.02
SSBOND 3 CYS A 269 CYS A 319 1555 1555 2.03
LINK ND1 HIS A 396 ZN ZN A 503 1555 1555 2.04
LINK NE2 HIS A 398 ZN ZN A 503 1555 1555 2.13
CISPEP 1 SER A 22 PRO A 23 0 -4.26
CISPEP 2 ARG A 128 PRO A 129 0 6.34
CISPEP 3 TYR A 222 ASP A 223 0 5.30
CISPEP 4 GLY A 372 PRO A 373 0 -5.91
SITE 1 AC1 17 GLY A 11 GLN A 12 GLY A 13 LEU A 30
SITE 2 AC1 17 ASP A 32 TYR A 71 THR A 72 GLN A 73
SITE 3 AC1 17 GLY A 74 LYS A 75 LYS A 107 PHE A 108
SITE 4 AC1 17 ILE A 110 GLY A 230 HOH A 909 HOH A 982
SITE 5 AC1 17 HOH A1007
SITE 1 AC2 3 ASP A 131 HIS A 396 HOH A1021
SITE 1 AC3 4 GLU A 255 ASP A 390 HIS A 396 HIS A 398
CRYST1 74.471 103.905 100.682 90.00 90.00 90.00 C 2 2 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 0.013428 0.000000 0.000000 0.00000
SCALE2 0.000000 0.009624 0.000000 0.00000
SCALE3 0.000000 0.000000 0.009932 0.00000
(ATOM LINES ARE NOT SHOWN.)
END
