HEADER HYDROLASE 21-DEC-09 3L5E
TITLE STRUCTURE OF BACE BOUND TO SCH736062
COMPND MOL_ID: 1;
COMPND 2 MOLECULE: BETA-SECRETASE 1;
COMPND 3 CHAIN: A, B;
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: BACE, BACE1, KIAA1149;
SOURCE 6 EXPRESSION_SYSTEM: ESCHERICHIA COLI;
SOURCE 7 EXPRESSION_SYSTEM_TAXID: 562;
SOURCE 8 EXPRESSION_SYSTEM_STRAIN: BL21(DE3);
SOURCE 9 EXPRESSION_SYSTEM_VECTOR_TYPE: PET11A
KEYWDS BACE1, ALZHEIMERS, ALTERNATIVE SPLICING, ASPARTYL PROTEASE, DISULFIDE
KEYWDS 2 BOND, ENDOPLASMIC RETICULUM, ENDOSOME, GLYCOPROTEIN, GOLGI
KEYWDS 3 APPARATUS, HYDROLASE, MEMBRANE, POLYMORPHISM, PROTEASE,
KEYWDS 4 TRANSMEMBRANE, ZYMOGEN
EXPDTA X-RAY DIFFRACTION
AUTHOR C.STRICKLAND,Z.ZHU
REVDAT 2 01-NOV-17 3L5E 1 REMARK
REVDAT 1 16-FEB-10 3L5E 0
JRNL AUTH Z.ZHU,Z.Y.SUN,Y.YE,J.VOIGT,C.STRICKLAND,E.M.SMITH,J.CUMMING,
JRNL AUTH 2 L.WANG,J.WONG,Y.S.WANG,D.F.WYSS,X.CHEN,R.KUVELKAR,
JRNL AUTH 3 M.E.KENNEDY,L.FAVREAU,E.PARKER,B.A.MCKITTRICK,A.STAMFORD,
JRNL AUTH 4 M.CZARNIECKI,W.GREENLEE,J.C.HUNTER
JRNL TITL DISCOVERY OF CYCLIC ACYLGUANIDINES AS HIGHLY POTENT AND
JRNL TITL 2 SELECTIVE BETA-SITE AMYLOID CLEAVING ENZYME (BACE)
JRNL TITL 3 INHIBITORS: PART I-INHIBITOR DESIGN AND VALIDATION
JRNL REF J.MED.CHEM. V. 53 951 2010
JRNL REFN ISSN 0022-2623
JRNL PMID 20043696
JRNL DOI 10.1021/JM901408P
REMARK 2
REMARK 2 RESOLUTION. 1.53 ANGSTROMS.
REMARK 3
REMARK 3 REFINEMENT.
REMARK 3 PROGRAM : CNS
REMARK 3 AUTHORS : BRUNGER,ADAMS,CLORE,DELANO,GROS,GROSSE-
REMARK 3 : KUNSTLEVE,JIANG,KUSZEWSKI,NILGES,PANNU,
REMARK 3 : READ,RICE,SIMONSON,WARREN
REMARK 3
REMARK 3 REFINEMENT TARGET : NULL
REMARK 3
REMARK 3 DATA USED IN REFINEMENT.
REMARK 3 RESOLUTION RANGE HIGH (ANGSTROMS) : 1.53
REMARK 3 RESOLUTION RANGE LOW (ANGSTROMS) : 20.00
REMARK 3 DATA CUTOFF (SIGMA(F)) : 0.000
REMARK 3 DATA CUTOFF HIGH (ABS(F)) : NULL
REMARK 3 DATA CUTOFF LOW (ABS(F)) : NULL
REMARK 3 COMPLETENESS (WORKING+TEST) (%) : 96.0
REMARK 3 NUMBER OF REFLECTIONS : 146870
REMARK 3
REMARK 3 FIT TO DATA USED IN REFINEMENT.
REMARK 3 CROSS-VALIDATION METHOD : NULL
REMARK 3 FREE R VALUE TEST SET SELECTION : NULL
REMARK 3 R VALUE (WORKING SET) : 0.186
REMARK 3 FREE R VALUE : 0.200
REMARK 3 FREE R VALUE TEST SET SIZE (%) : 4.800
REMARK 3 FREE R VALUE TEST SET COUNT : 7383
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 : NULL
REMARK 3 BIN RESOLUTION RANGE HIGH (A) : NULL
REMARK 3 BIN RESOLUTION RANGE LOW (A) : NULL
REMARK 3 BIN COMPLETENESS (WORKING+TEST) (%) : NULL
REMARK 3 REFLECTIONS IN BIN (WORKING SET) : NULL
REMARK 3 BIN R VALUE (WORKING SET) : NULL
REMARK 3 BIN FREE R VALUE : NULL
REMARK 3 BIN FREE R VALUE TEST SET SIZE (%) : NULL
REMARK 3 BIN FREE R VALUE TEST SET COUNT : NULL
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 : 6092
REMARK 3 NUCLEIC ACID ATOMS : 0
REMARK 3 HETEROGEN ATOMS : 108
REMARK 3 SOLVENT ATOMS : 882
REMARK 3
REMARK 3 B VALUES.
REMARK 3 FROM WILSON PLOT (A**2) : NULL
REMARK 3 MEAN B VALUE (OVERALL, A**2) : NULL
REMARK 3 OVERALL ANISOTROPIC B VALUE.
REMARK 3 B11 (A**2) : NULL
REMARK 3 B22 (A**2) : NULL
REMARK 3 B33 (A**2) : NULL
REMARK 3 B12 (A**2) : NULL
REMARK 3 B13 (A**2) : NULL
REMARK 3 B23 (A**2) : NULL
REMARK 3
REMARK 3 ESTIMATED COORDINATE ERROR.
REMARK 3 ESD FROM LUZZATI PLOT (A) : NULL
REMARK 3 ESD FROM SIGMAA (A) : NULL
REMARK 3 LOW RESOLUTION CUTOFF (A) : NULL
REMARK 3
REMARK 3 CROSS-VALIDATED ESTIMATED COORDINATE ERROR.
REMARK 3 ESD FROM C-V LUZZATI PLOT (A) : NULL
REMARK 3 ESD FROM C-V SIGMAA (A) : NULL
REMARK 3
REMARK 3 RMS DEVIATIONS FROM IDEAL VALUES.
REMARK 3 BOND LENGTHS (A) : 0.009
REMARK 3 BOND ANGLES (DEGREES) : NULL
REMARK 3 DIHEDRAL ANGLES (DEGREES) : NULL
REMARK 3 IMPROPER ANGLES (DEGREES) : NULL
REMARK 3
REMARK 3 ISOTROPIC THERMAL MODEL : NULL
REMARK 3
REMARK 3 ISOTROPIC THERMAL FACTOR RESTRAINTS. RMS SIGMA
REMARK 3 MAIN-CHAIN BOND (A**2) : NULL ; NULL
REMARK 3 MAIN-CHAIN ANGLE (A**2) : NULL ; NULL
REMARK 3 SIDE-CHAIN BOND (A**2) : NULL ; NULL
REMARK 3 SIDE-CHAIN ANGLE (A**2) : NULL ; NULL
REMARK 3
REMARK 3 BULK SOLVENT MODELING.
REMARK 3 METHOD USED : NULL
REMARK 3 KSOL : NULL
REMARK 3 BSOL : NULL
REMARK 3
REMARK 3 NCS MODEL : NULL
REMARK 3
REMARK 3 NCS RESTRAINTS. RMS SIGMA/WEIGHT
REMARK 3 GROUP 1 POSITIONAL (A) : NULL ; NULL
REMARK 3 GROUP 1 B-FACTOR (A**2) : NULL ; NULL
REMARK 3
REMARK 3 PARAMETER FILE 1 : MSI_CNX_TOPPAR:PROTEIN_REP.PARAM
REMARK 3 PARAMETER FILE 2 : MSI_CNX_TOPPAR:ION.PARAM
REMARK 3 PARAMETER FILE 3 : MSI_CNX_TOPPAR:WATER_REP.PARAM
REMARK 3 PARAMETER FILE 4 : PARATARTRATE.PRO
REMARK 3 PARAMETER FILE 5 : PARASCH736062.PRO
REMARK 3 PARAMETER FILE 6 : NULL
REMARK 3 TOPOLOGY FILE 1 : MSI_CNX_TOPPAR:PROTEIN.TOP
REMARK 3 TOPOLOGY FILE 2 : MSI_CNX_TOPPAR:ION.TOP
REMARK 3 TOPOLOGY FILE 3 : MSI_CNX_TOPPAR:WATER.TOP
REMARK 3 TOPOLOGY FILE 4 : TOPTARTRATE.PRO
REMARK 3 TOPOLOGY FILE 5 : TOPSCH736062.PRO
REMARK 3 TOPOLOGY FILE 6 : NULL
REMARK 3
REMARK 3 OTHER REFINEMENT REMARKS: NULL
REMARK 4
REMARK 4 3L5E COMPLIES WITH FORMAT V. 3.30, 13-JUL-11
REMARK 100
REMARK 100 THIS ENTRY HAS BEEN PROCESSED BY RCSB ON 11-JAN-10.
REMARK 100 THE DEPOSITION ID IS D_1000056854.
REMARK 200
REMARK 200 EXPERIMENTAL DETAILS
REMARK 200 EXPERIMENT TYPE : X-RAY DIFFRACTION
REMARK 200 DATE OF DATA COLLECTION : 09-FEB-04
REMARK 200 TEMPERATURE (KELVIN) : 95
REMARK 200 PH : NULL
REMARK 200 NUMBER OF CRYSTALS USED : 1
REMARK 200
REMARK 200 SYNCHROTRON (Y/N) : Y
REMARK 200 RADIATION SOURCE : APS
REMARK 200 BEAMLINE : 17-ID
REMARK 200 X-RAY GENERATOR MODEL : NULL
REMARK 200 MONOCHROMATIC OR LAUE (M/L) : M
REMARK 200 WAVELENGTH OR RANGE (A) : 1.000
REMARK 200 MONOCHROMATOR : NULL
REMARK 200 OPTICS : NULL
REMARK 200
REMARK 200 DETECTOR TYPE : CCD
REMARK 200 DETECTOR MANUFACTURER : ADSC QUANTUM 210
REMARK 200 INTENSITY-INTEGRATION SOFTWARE : DENZO
REMARK 200 DATA SCALING SOFTWARE : SCALEPACK
REMARK 200
REMARK 200 NUMBER OF UNIQUE REFLECTIONS : 146950
REMARK 200 RESOLUTION RANGE HIGH (A) : 1.530
REMARK 200 RESOLUTION RANGE LOW (A) : 20.000
REMARK 200 REJECTION CRITERIA (SIGMA(I)) : NULL
REMARK 200
REMARK 200 OVERALL.
REMARK 200 COMPLETENESS FOR RANGE (%) : 96.4
REMARK 200 DATA REDUNDANCY : NULL
REMARK 200 R MERGE (I) : 0.05700
REMARK 200 R SYM (I) : NULL
REMARK 200 <I/SIGMA(I)> FOR THE DATA SET : 11.0000
REMARK 200
REMARK 200 IN THE HIGHEST RESOLUTION SHELL.
REMARK 200 HIGHEST RESOLUTION SHELL, RANGE HIGH (A) : 1.53
REMARK 200 HIGHEST RESOLUTION SHELL, RANGE LOW (A) : 1.56
REMARK 200 COMPLETENESS FOR SHELL (%) : 92.8
REMARK 200 DATA REDUNDANCY IN SHELL : NULL
REMARK 200 R MERGE FOR SHELL (I) : 0.56700
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 (%): 54.98
REMARK 280 MATTHEWS COEFFICIENT, VM (ANGSTROMS**3/DA): 2.73
REMARK 280
REMARK 280 CRYSTALLIZATION CONDITIONS: 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 43.23900
REMARK 290 SMTRY2 2 0.000000 -1.000000 0.000000 0.00000
REMARK 290 SMTRY3 2 0.000000 0.000000 1.000000 65.32250
REMARK 290 SMTRY1 3 -1.000000 0.000000 0.000000 0.00000
REMARK 290 SMTRY2 3 0.000000 1.000000 0.000000 44.73450
REMARK 290 SMTRY3 3 0.000000 0.000000 -1.000000 65.32250
REMARK 290 SMTRY1 4 1.000000 0.000000 0.000000 43.23900
REMARK 290 SMTRY2 4 0.000000 -1.000000 0.000000 44.73450
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 LEU A 41
REMARK 465 ARG A 42
REMARK 465 LEU A 43
REMARK 465 PRO A 44
REMARK 465 ARG A 45
REMARK 465 GLU A 46
REMARK 465 THR A 47
REMARK 465 ASP A 48
REMARK 465 GLU A 49
REMARK 465 GLU A 50
REMARK 465 PRO A 51
REMARK 465 GLU A 52
REMARK 465 GLU A 53
REMARK 465 PRO A 54
REMARK 465 GLY A 55
REMARK 465 ARG A 56
REMARK 465 ARG A 57
REMARK 465 PRO A 448
REMARK 465 GLN A 449
REMARK 465 THR A 450
REMARK 465 ASP A 451
REMARK 465 GLU A 452
REMARK 465 SER A 453
REMARK 465 THR A 454
REMARK 465 LEU B 41
REMARK 465 ARG B 42
REMARK 465 LEU B 43
REMARK 465 PRO B 44
REMARK 465 ARG B 45
REMARK 465 GLU B 46
REMARK 465 THR B 47
REMARK 465 ASP B 48
REMARK 465 GLU B 49
REMARK 465 GLU B 50
REMARK 465 PRO B 51
REMARK 465 GLU B 52
REMARK 465 GLU B 53
REMARK 465 PRO B 54
REMARK 465 GLY B 55
REMARK 465 ARG B 56
REMARK 465 ARG B 57
REMARK 465 THR B 133
REMARK 465 GLN B 134
REMARK 465 GLY B 135
REMARK 465 ILE B 447
REMARK 465 PRO B 448
REMARK 465 GLN B 449
REMARK 465 THR B 450
REMARK 465 ASP B 451
REMARK 465 GLU B 452
REMARK 465 SER B 453
REMARK 465 THR B 454
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 B 653 O HOH B 702 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 THR A 133 -71.63 -33.56
REMARK 500 HIS A 150 62.75 -105.75
REMARK 500 PHE A 169 -66.66 -108.90
REMARK 500 TRP A 258 -81.03 -145.28
REMARK 500 THR A 375 23.79 39.75
REMARK 500 SER A 376 -166.53 -55.61
REMARK 500 HIS B 150 54.43 -109.46
REMARK 500 ASP B 192 1.94 -66.32
REMARK 500 TRP B 258 -83.28 -143.65
REMARK 500 ALA B 333 123.50 -39.74
REMARK 500 SER B 376 -172.06 -61.59
REMARK 500 ALA B 384 36.82 -99.45
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 TAR A 2
REMARK 800
REMARK 800 SITE_IDENTIFIER: AC2
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: BINDING SITE FOR RESIDUE BDW A 1
REMARK 800
REMARK 800 SITE_IDENTIFIER: AC3
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: BINDING SITE FOR RESIDUE TAR B 1
REMARK 800
REMARK 800 SITE_IDENTIFIER: AC4
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: BINDING SITE FOR RESIDUE TAR B 3
REMARK 800
REMARK 800 SITE_IDENTIFIER: AC5
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: BINDING SITE FOR RESIDUE BDW B 455
REMARK 900
REMARK 900 RELATED ENTRIES
REMARK 900 RELATED ID: 3L58 RELATED DB: PDB
REMARK 900 RELATED ID: 3L59 RELATED DB: PDB
REMARK 900 RELATED ID: 3L5B RELATED DB: PDB
REMARK 900 RELATED ID: 3L5C RELATED DB: PDB
REMARK 900 RELATED ID: 3L5D RELATED DB: PDB
REMARK 900 RELATED ID: 3L5F RELATED DB: PDB
DBREF 3L5E A 41 454 UNP P56817 BACE1_HUMAN 41 454
DBREF 3L5E B 41 454 UNP P56817 BACE1_HUMAN 41 454
SEQRES 1 A 414 LEU ARG LEU PRO ARG GLU THR ASP GLU GLU PRO GLU GLU
SEQRES 2 A 414 PRO GLY ARG ARG GLY SER PHE VAL GLU MET VAL ASP ASN
SEQRES 3 A 414 LEU ARG GLY LYS SER GLY GLN GLY TYR TYR VAL GLU MET
SEQRES 4 A 414 THR VAL GLY SER PRO PRO GLN THR LEU ASN ILE LEU VAL
SEQRES 5 A 414 ASP THR GLY SER SER ASN PHE ALA VAL GLY ALA ALA PRO
SEQRES 6 A 414 HIS PRO PHE LEU HIS ARG TYR TYR GLN ARG GLN LEU SER
SEQRES 7 A 414 SER THR TYR ARG ASP LEU ARG LYS GLY VAL TYR VAL PRO
SEQRES 8 A 414 TYR THR GLN GLY LYS TRP GLU GLY GLU LEU GLY THR ASP
SEQRES 9 A 414 LEU VAL SER ILE PRO HIS GLY PRO ASN VAL THR VAL ARG
SEQRES 10 A 414 ALA ASN ILE ALA ALA ILE THR GLU SER ASP LYS PHE PHE
SEQRES 11 A 414 ILE ASN GLY SER ASN TRP GLU GLY ILE LEU GLY LEU ALA
SEQRES 12 A 414 TYR ALA GLU ILE ALA ARG PRO ASP ASP SER LEU GLU PRO
SEQRES 13 A 414 PHE PHE ASP SER LEU VAL LYS GLN THR HIS VAL PRO ASN
SEQRES 14 A 414 LEU PHE SER LEU GLN LEU CYS GLY ALA GLY PHE PRO LEU
SEQRES 15 A 414 ASN GLN SER GLU VAL LEU ALA SER VAL GLY GLY SER MET
SEQRES 16 A 414 ILE ILE GLY GLY ILE ASP HIS SER LEU TYR THR GLY SER
SEQRES 17 A 414 LEU TRP TYR THR PRO ILE ARG ARG GLU TRP TYR TYR GLU
SEQRES 18 A 414 VAL ILE ILE VAL ARG VAL GLU ILE ASN GLY GLN ASP LEU
SEQRES 19 A 414 LYS MET ASP CYS LYS GLU TYR ASN TYR ASP LYS SER ILE
SEQRES 20 A 414 VAL ASP SER GLY THR THR ASN LEU ARG LEU PRO LYS LYS
SEQRES 21 A 414 VAL PHE GLU ALA ALA VAL LYS SER ILE LYS ALA ALA SER
SEQRES 22 A 414 SER THR GLU LYS PHE PRO ASP GLY PHE TRP LEU GLY GLU
SEQRES 23 A 414 GLN LEU VAL CYS TRP GLN ALA GLY THR THR PRO TRP ASN
SEQRES 24 A 414 ILE PHE PRO VAL ILE SER LEU TYR LEU MET GLY GLU VAL
SEQRES 25 A 414 THR ASN GLN SER PHE ARG ILE THR ILE LEU PRO GLN GLN
SEQRES 26 A 414 TYR LEU ARG PRO VAL GLU ASP VAL ALA THR SER GLN ASP
SEQRES 27 A 414 ASP CYS TYR LYS PHE ALA ILE SER GLN SER SER THR GLY
SEQRES 28 A 414 THR VAL MET GLY ALA VAL ILE MET GLU GLY PHE TYR VAL
SEQRES 29 A 414 VAL PHE ASP ARG ALA ARG LYS ARG ILE GLY PHE ALA VAL
SEQRES 30 A 414 SER ALA CYS HIS VAL HIS ASP GLU PHE ARG THR ALA ALA
SEQRES 31 A 414 VAL GLU GLY PRO PHE VAL THR LEU ASP MET GLU ASP CYS
SEQRES 32 A 414 GLY TYR ASN ILE PRO GLN THR ASP GLU SER THR
SEQRES 1 B 414 LEU ARG LEU PRO ARG GLU THR ASP GLU GLU PRO GLU GLU
SEQRES 2 B 414 PRO GLY ARG ARG GLY SER PHE VAL GLU MET VAL ASP ASN
SEQRES 3 B 414 LEU ARG GLY LYS SER GLY GLN GLY TYR TYR VAL GLU MET
SEQRES 4 B 414 THR VAL GLY SER PRO PRO GLN THR LEU ASN ILE LEU VAL
SEQRES 5 B 414 ASP THR GLY SER SER ASN PHE ALA VAL GLY ALA ALA PRO
SEQRES 6 B 414 HIS PRO PHE LEU HIS ARG TYR TYR GLN ARG GLN LEU SER
SEQRES 7 B 414 SER THR TYR ARG ASP LEU ARG LYS GLY VAL TYR VAL PRO
SEQRES 8 B 414 TYR THR GLN GLY LYS TRP GLU GLY GLU LEU GLY THR ASP
SEQRES 9 B 414 LEU VAL SER ILE PRO HIS GLY PRO ASN VAL THR VAL ARG
SEQRES 10 B 414 ALA ASN ILE ALA ALA ILE THR GLU SER ASP LYS PHE PHE
SEQRES 11 B 414 ILE ASN GLY SER ASN TRP GLU GLY ILE LEU GLY LEU ALA
SEQRES 12 B 414 TYR ALA GLU ILE ALA ARG PRO ASP ASP SER LEU GLU PRO
SEQRES 13 B 414 PHE PHE ASP SER LEU VAL LYS GLN THR HIS VAL PRO ASN
SEQRES 14 B 414 LEU PHE SER LEU GLN LEU CYS GLY ALA GLY PHE PRO LEU
SEQRES 15 B 414 ASN GLN SER GLU VAL LEU ALA SER VAL GLY GLY SER MET
SEQRES 16 B 414 ILE ILE GLY GLY ILE ASP HIS SER LEU TYR THR GLY SER
SEQRES 17 B 414 LEU TRP TYR THR PRO ILE ARG ARG GLU TRP TYR TYR GLU
SEQRES 18 B 414 VAL ILE ILE VAL ARG VAL GLU ILE ASN GLY GLN ASP LEU
SEQRES 19 B 414 LYS MET ASP CYS LYS GLU TYR ASN TYR ASP LYS SER ILE
SEQRES 20 B 414 VAL ASP SER GLY THR THR ASN LEU ARG LEU PRO LYS LYS
SEQRES 21 B 414 VAL PHE GLU ALA ALA VAL LYS SER ILE LYS ALA ALA SER
SEQRES 22 B 414 SER THR GLU LYS PHE PRO ASP GLY PHE TRP LEU GLY GLU
SEQRES 23 B 414 GLN LEU VAL CYS TRP GLN ALA GLY THR THR PRO TRP ASN
SEQRES 24 B 414 ILE PHE PRO VAL ILE SER LEU TYR LEU MET GLY GLU VAL
SEQRES 25 B 414 THR ASN GLN SER PHE ARG ILE THR ILE LEU PRO GLN GLN
SEQRES 26 B 414 TYR LEU ARG PRO VAL GLU ASP VAL ALA THR SER GLN ASP
SEQRES 27 B 414 ASP CYS TYR LYS PHE ALA ILE SER GLN SER SER THR GLY
SEQRES 28 B 414 THR VAL MET GLY ALA VAL ILE MET GLU GLY PHE TYR VAL
SEQRES 29 B 414 VAL PHE ASP ARG ALA ARG LYS ARG ILE GLY PHE ALA VAL
SEQRES 30 B 414 SER ALA CYS HIS VAL HIS ASP GLU PHE ARG THR ALA ALA
SEQRES 31 B 414 VAL GLU GLY PRO PHE VAL THR LEU ASP MET GLU ASP CYS
SEQRES 32 B 414 GLY TYR ASN ILE PRO GLN THR ASP GLU SER THR
HET TAR A 2 10
HET BDW A 1 39
HET TAR B 1 10
HET TAR B 3 10
HET BDW B 455 39
HETNAM TAR D(-)-TARTARIC ACID
HETNAM BDW (4S)-1-(4-{[(2Z,4R)-4-(2-CYCLOHEXYLETHYL)-4-
HETNAM 2 BDW (CYCLOHEXYLMETHYL)-2-IMINO-5-OXOIMIDAZOLIDIN-1-
HETNAM 3 BDW YL]METHYL}BENZYL)-4-PROPYLIMIDAZOLIDIN-2-ONE
FORMUL 3 TAR 3(C4 H6 O6)
FORMUL 4 BDW 2(C32 H49 N5 O2)
FORMUL 8 HOH *882(H2 O)
HELIX 1 1 GLN A 114 SER A 118 5 5
HELIX 2 2 TYR A 184 ALA A 188 5 5
HELIX 3 3 PRO A 196 THR A 205 1 10
HELIX 4 4 ASN A 223 SER A 230 1 8
HELIX 5 5 ASP A 241 SER A 243 5 3
HELIX 6 6 ASP A 277 TYR A 283 5 7
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 ASP A 439 GLY A 444 5 6
HELIX 13 13 GLN B 114 SER B 118 5 5
HELIX 14 14 TYR B 184 ALA B 188 5 5
HELIX 15 15 PRO B 196 THR B 205 1 10
HELIX 16 16 ASN B 223 SER B 230 1 8
HELIX 17 17 ASP B 241 SER B 243 5 3
HELIX 18 18 ASP B 277 ASN B 282 1 6
HELIX 19 19 LYS B 299 SER B 313 1 15
HELIX 20 20 PRO B 319 LEU B 324 1 6
HELIX 21 21 PRO B 337 PHE B 341 5 5
HELIX 22 22 LEU B 362 TYR B 366 1 5
HELIX 23 23 GLY B 395 GLU B 400 1 6
HELIX 24 24 ASP B 439 GLY B 444 5 6
SHEET 1 A 8 LEU A 67 LYS A 70 0
SHEET 2 A 8 GLY A 74 VAL A 81 -1 O TYR A 76 N ARG A 68
SHEET 3 A 8 GLN A 86 ASP A 93 -1 O VAL A 92 N TYR A 75
SHEET 4 A 8 GLY A 178 GLY A 181 1 O LEU A 180 N LEU A 91
SHEET 5 A 8 PHE A 99 GLY A 102 -1 N ALA A 100 O ILE A 179
SHEET 6 A 8 THR A 155 ASP A 167 1 O ILE A 163 N VAL A 101
SHEET 7 A 8 GLY A 135 SER A 147 -1 N GLU A 140 O ALA A 162
SHEET 8 A 8 ARG A 122 TYR A 132 -1 N LYS A 126 O LEU A 141
SHEET 1 B 4 LEU A 67 LYS A 70 0
SHEET 2 B 4 GLY A 74 VAL A 81 -1 O TYR A 76 N ARG A 68
SHEET 3 B 4 GLY A 135 SER A 147 -1 O SER A 147 N THR A 80
SHEET 4 B 4 ARG A 122 TYR A 132 -1 N LYS A 126 O LEU A 141
SHEET 1 C 5 GLY A 233 ILE A 237 0
SHEET 2 C 5 PHE A 211 LEU A 215 -1 N GLN A 214 O SER A 234
SHEET 3 C 5 PHE A 402 ASP A 407 -1 O VAL A 404 N LEU A 213
SHEET 4 C 5 ARG A 412 SER A 418 -1 O ALA A 416 N TYR A 403
SHEET 5 C 5 TYR A 245 PRO A 253 -1 N THR A 252 O ILE A 413
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 4 SER A 286 VAL A 288 0
SHEET 2 E 4 THR A 392 MET A 394 1 O MET A 394 N ILE A 287
SHEET 3 E 4 LEU A 295 PRO A 298 -1 N ARG A 296 O VAL A 393
SHEET 4 E 4 ILE A 385 SER A 388 1 O SER A 386 N LEU A 297
SHEET 1 F 3 VAL A 329 TRP A 331 0
SHEET 2 F 3 ASP A 379 PHE A 383 -1 O ASP A 379 N TRP A 331
SHEET 3 F 3 LEU A 367 VAL A 370 -1 N ARG A 368 O LYS A 382
SHEET 1 G 8 LEU B 67 LYS B 70 0
SHEET 2 G 8 GLY B 74 VAL B 81 -1 O TYR B 76 N ARG B 68
SHEET 3 G 8 GLN B 86 ASP B 93 -1 O VAL B 92 N TYR B 75
SHEET 4 G 8 GLY B 178 GLY B 181 1 O LEU B 180 N LEU B 91
SHEET 5 G 8 PHE B 99 GLY B 102 -1 N ALA B 100 O ILE B 179
SHEET 6 G 8 THR B 155 SER B 166 1 O ILE B 163 N VAL B 101
SHEET 7 G 8 TRP B 137 SER B 147 -1 N GLU B 140 O ALA B 162
SHEET 8 G 8 ARG B 122 VAL B 130 -1 N LYS B 126 O LEU B 141
SHEET 1 H 4 LEU B 67 LYS B 70 0
SHEET 2 H 4 GLY B 74 VAL B 81 -1 O TYR B 76 N ARG B 68
SHEET 3 H 4 TRP B 137 SER B 147 -1 O SER B 147 N THR B 80
SHEET 4 H 4 ARG B 122 VAL B 130 -1 N LYS B 126 O LEU B 141
SHEET 1 I 5 GLY B 233 ILE B 237 0
SHEET 2 I 5 PHE B 211 LEU B 215 -1 N GLN B 214 O SER B 234
SHEET 3 I 5 PHE B 402 ASP B 407 -1 O VAL B 404 N LEU B 213
SHEET 4 I 5 ARG B 412 SER B 418 -1 O ALA B 416 N TYR B 403
SHEET 5 I 5 TYR B 245 PRO B 253 -1 N THR B 252 O ILE B 413
SHEET 1 J 5 GLN B 272 ASP B 273 0
SHEET 2 J 5 ILE B 264 ILE B 269 -1 N ILE B 269 O GLN B 272
SHEET 3 J 5 ILE B 344 MET B 349 -1 O TYR B 347 N ARG B 266
SHEET 4 J 5 GLN B 355 ILE B 361 -1 O ILE B 361 N ILE B 344
SHEET 5 J 5 ALA B 430 VAL B 436 -1 O GLU B 432 N ARG B 358
SHEET 1 K 4 SER B 286 VAL B 288 0
SHEET 2 K 4 THR B 392 MET B 394 1 O MET B 394 N ILE B 287
SHEET 3 K 4 LEU B 295 PRO B 298 -1 N ARG B 296 O VAL B 393
SHEET 4 K 4 ILE B 385 SER B 388 1 O SER B 388 N LEU B 297
SHEET 1 L 3 VAL B 329 TRP B 331 0
SHEET 2 L 3 ASP B 379 PHE B 383 -1 O ASP B 379 N TRP B 331
SHEET 3 L 3 LEU B 367 VAL B 370 -1 N ARG B 368 O LYS B 382
SSBOND 1 CYS A 216 CYS A 420 1555 1555 2.06
SSBOND 2 CYS A 278 CYS A 443 1555 1555 2.04
SSBOND 3 CYS A 330 CYS A 380 1555 1555 2.05
SSBOND 4 CYS B 216 CYS B 420 1555 1555 2.07
SSBOND 5 CYS B 278 CYS B 443 1555 1555 2.04
SSBOND 6 CYS B 330 CYS B 380 1555 1555 2.05
CISPEP 1 SER A 83 PRO A 84 0 -0.42
CISPEP 2 ARG A 189 PRO A 190 0 0.49
CISPEP 3 TYR A 283 ASP A 284 0 6.05
CISPEP 4 GLY A 433 PRO A 434 0 -0.16
CISPEP 5 SER B 83 PRO B 84 0 -0.12
CISPEP 6 ARG B 189 PRO B 190 0 0.34
CISPEP 7 TYR B 283 ASP B 284 0 1.87
CISPEP 8 GLY B 433 PRO B 434 0 -0.27
SITE 1 AC1 9 ARG A 68 ASN A 89 HIS A 110 ARG A 111
SITE 2 AC1 9 ASN A 175 HOH A 553 HOH A 612 HOH A 627
SITE 3 AC1 9 HOH A 789
SITE 1 AC2 12 ASP A 93 GLY A 95 TYR A 132 ILE A 171
SITE 2 AC2 12 ILE A 187 ARG A 189 ASP A 289 GLY A 291
SITE 3 AC2 12 THR A 292 THR A 293 HOH A 844 HOH A 855
SITE 1 AC3 9 LYS A 300 HIS B 106 PHE B 108 SER B 166
SITE 2 AC3 9 ASP B 167 LYS B 168 PHE B 169 PHE B 170
SITE 3 AC3 9 HOH B 484
SITE 1 AC4 9 ARG B 68 ASN B 89 HIS B 110 ARG B 111
SITE 2 AC4 9 ASN B 175 HOH B 522 HOH B 586 HOH B 671
SITE 3 AC4 9 HOH B 676
SITE 1 AC5 13 GLN B 73 LEU B 91 ASP B 93 GLY B 95
SITE 2 AC5 13 SER B 96 VAL B 130 ILE B 187 ARG B 189
SITE 3 AC5 13 ASP B 289 GLY B 291 THR B 292 THR B 293
SITE 4 AC5 13 HOH B 813
CRYST1 86.478 89.469 130.645 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 0.011564 0.000000 0.000000 0.00000
SCALE2 0.000000 0.011177 0.000000 0.00000
SCALE3 0.000000 0.000000 0.007654 0.00000
(ATOM LINES ARE NOT SHOWN.)
END
