HEADER HYDROLASE 11-NOV-09 3KN0
TITLE STRUCTURE OF BACE BOUND TO SCH708236
COMPND MOL_ID: 1;
COMPND 2 MOLECULE: BETA-SECRETASE 1;
COMPND 3 CHAIN: A, B;
COMPND 4 FRAGMENT: UNP RESIDUES 55-447;
COMPND 5 SYNONYM: BETA-SITE AMYLOID PROTEIN CLEAVING ENZYME 1, BETA-SITE AP
COMPND 6 CLEAVING ENZYME 1, MEMBRANE-ASSOCIATED ASPARTIC PROTEASE 2, MEMAPSIN-
COMPND 7 2, ASPARTYL PROTEASE 2, ASP 2, ASP2;
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: 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: PLASMID;
SOURCE 10 EXPRESSION_SYSTEM_PLASMID: PET11A
KEYWDS BACE1, ALZHEIMER'S, ALTERNATIVE SPLICING, ASPARTYL PROTEASE,
KEYWDS 2 DISULFIDE BOND, ENDOPLASMIC RETICULUM, ENDOSOME, GLYCOPROTEIN, GOLGI
KEYWDS 3 APPARATUS, HYDROLASE, MEMBRANE, POLYMORPHISM, PROTEASE,
KEYWDS 4 TRANSMEMBRANE, ZYMOGEN
EXPDTA X-RAY DIFFRACTION
AUTHOR C.STRICKLAND,Y.WANG
REVDAT 4 06-SEP-23 3KN0 1 REMARK
REVDAT 3 01-NOV-17 3KN0 1 REMARK
REVDAT 2 16-FEB-10 3KN0 1 JRNL
REVDAT 1 19-JAN-10 3KN0 0
JRNL AUTH Y.S.WANG,C.STRICKLAND,J.H.VOIGT,M.E.KENNEDY,B.M.BEYER,
JRNL AUTH 2 M.M.SENIOR,E.M.SMITH,T.L.NECHUTA,V.S.MADISON,M.CZARNIECKI,
JRNL AUTH 3 B.A.MCKITTRICK,A.W.STAMFORD,E.M.PARKER,J.C.HUNTER,
JRNL AUTH 4 W.J.GREENLEE,D.F.WYSS
JRNL TITL APPLICATION OF FRAGMENT-BASED NMR SCREENING, X-RAY
JRNL TITL 2 CRYSTALLOGRAPHY, STRUCTURE-BASED DESIGN, AND FOCUSED
JRNL TITL 3 CHEMICAL LIBRARY DESIGN TO IDENTIFY NOVEL MUM LEADS FOR THE
JRNL TITL 4 DEVELOPMENT OF NM BACE-1 (BETA-SITE APP CLEAVING ENZYME 1)
JRNL TITL 5 INHIBITORS.
JRNL REF J.MED.CHEM. V. 53 942 2010
JRNL REFN ISSN 0022-2623
JRNL PMID 20043700
JRNL DOI 10.1021/JM901472U
REMARK 2
REMARK 2 RESOLUTION. 1.90 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 DATA USED IN REFINEMENT.
REMARK 3 RESOLUTION RANGE HIGH (ANGSTROMS) : 1.90
REMARK 3 RESOLUTION RANGE LOW (ANGSTROMS) : 50.00
REMARK 3 DATA CUTOFF (SIGMA(F)) : NULL
REMARK 3 DATA CUTOFF HIGH (ABS(F)) : NULL
REMARK 3 DATA CUTOFF LOW (ABS(F)) : NULL
REMARK 3 COMPLETENESS (WORKING+TEST) (%) : NULL
REMARK 3 NUMBER OF REFLECTIONS : 80633
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 + TEST SET) : 0.188
REMARK 3 R VALUE (WORKING SET) : 0.188
REMARK 3 FREE R VALUE : 0.222
REMARK 3 FREE R VALUE TEST SET SIZE (%) : NULL
REMARK 3 FREE R VALUE TEST SET COUNT : 4009
REMARK 3 ESTIMATED ERROR OF FREE R VALUE : NULL
REMARK 3
REMARK 3 FIT/AGREEMENT OF MODEL WITH ALL DATA.
REMARK 3 R VALUE (WORKING + TEST SET, NO CUTOFF) : NULL
REMARK 3 R VALUE (WORKING SET, NO CUTOFF) : NULL
REMARK 3 FREE R VALUE (NO CUTOFF) : NULL
REMARK 3 FREE R VALUE TEST SET SIZE (%, NO CUTOFF) : NULL
REMARK 3 FREE R VALUE TEST SET COUNT (NO CUTOFF) : NULL
REMARK 3 ESTIMATED ERROR OF FREE R VALUE (NO CUTOFF) : NULL
REMARK 3 TOTAL NUMBER OF REFLECTIONS (NO CUTOFF) : 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 : 68
REMARK 3 SOLVENT ATOMS : 942
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) : NULL
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 : NULL
REMARK 3 TOPOLOGY FILE 1 : NULL
REMARK 3
REMARK 3 OTHER REFINEMENT REMARKS: NULL
REMARK 4
REMARK 4 3KN0 COMPLIES WITH FORMAT V. 3.30, 13-JUL-11
REMARK 100
REMARK 100 THIS ENTRY HAS BEEN PROCESSED BY RCSB ON 20-NOV-09.
REMARK 100 THE DEPOSITION ID IS D_1000056194.
REMARK 200
REMARK 200 EXPERIMENTAL DETAILS
REMARK 200 EXPERIMENT TYPE : X-RAY DIFFRACTION
REMARK 200 DATE OF DATA COLLECTION : 18-JUN-03
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-BM
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 : MAR CCD 165 MM
REMARK 200 INTENSITY-INTEGRATION SOFTWARE : DENZO
REMARK 200 DATA SCALING SOFTWARE : SCALEPACK
REMARK 200
REMARK 200 NUMBER OF UNIQUE REFLECTIONS : 86929
REMARK 200 RESOLUTION RANGE HIGH (A) : 1.850
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 (%) : 99.5
REMARK 200 DATA REDUNDANCY : NULL
REMARK 200 R MERGE (I) : 0.07100
REMARK 200 R SYM (I) : NULL
REMARK 200 <I/SIGMA(I)> FOR THE DATA SET : 8.8000
REMARK 200
REMARK 200 IN THE HIGHEST RESOLUTION SHELL.
REMARK 200 HIGHEST RESOLUTION SHELL, RANGE HIGH (A) : 1.85
REMARK 200 HIGHEST RESOLUTION SHELL, RANGE LOW (A) : 1.92
REMARK 200 COMPLETENESS FOR SHELL (%) : 100.0
REMARK 200 DATA REDUNDANCY IN SHELL : NULL
REMARK 200 R MERGE FOR SHELL (I) : 0.38700
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: CNX
REMARK 200 STARTING MODEL: PDB ENTRY 3KMX
REMARK 200
REMARK 200 REMARK: NULL
REMARK 280
REMARK 280 CRYSTAL
REMARK 280 SOLVENT CONTENT, VS (%): 57.46
REMARK 280 MATTHEWS COEFFICIENT, VM (ANGSTROMS**3/DA): 2.89
REMARK 280
REMARK 280 CRYSTALLIZATION CONDITIONS: VAPOR DIFFUSION, HANGING DROP
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 43.22400
REMARK 290 SMTRY2 2 0.000000 -1.000000 0.000000 0.00000
REMARK 290 SMTRY3 2 0.000000 0.000000 1.000000 65.63250
REMARK 290 SMTRY1 3 -1.000000 0.000000 0.000000 0.00000
REMARK 290 SMTRY2 3 0.000000 1.000000 0.000000 44.87050
REMARK 290 SMTRY3 3 0.000000 0.000000 -1.000000 65.63250
REMARK 290 SMTRY1 4 1.000000 0.000000 0.000000 43.22400
REMARK 290 SMTRY2 4 0.000000 -1.000000 0.000000 44.87050
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, 3
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: DIMERIC
REMARK 350 APPLY THE FOLLOWING TO CHAINS: A, 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: 2
REMARK 350 SOFTWARE DETERMINED QUATERNARY STRUCTURE: DIMERIC
REMARK 350 SOFTWARE USED: PISA
REMARK 350 APPLY THE FOLLOWING TO CHAINS: A, 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 SOFTWARE DETERMINED QUATERNARY STRUCTURE: DIMERIC
REMARK 350 SOFTWARE USED: PISA
REMARK 350 APPLY THE FOLLOWING TO CHAINS: A, 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 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 THR A 133
REMARK 465 GLN A 134
REMARK 465 GLY A 135
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 ILE B 447
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 150 64.86 -104.11
REMARK 500 PHE A 169 -60.37 -90.98
REMARK 500 LEU A 210 144.28 -170.11
REMARK 500 TRP A 258 -85.29 -147.30
REMARK 500 ALA A 333 124.11 -36.68
REMARK 500 VAL A 373 -6.76 -54.20
REMARK 500 THR A 375 13.20 52.12
REMARK 500 SER A 376 -166.93 -52.22
REMARK 500 ALA A 384 30.84 -97.19
REMARK 500 HIS B 150 53.83 -110.30
REMARK 500 ASP B 192 0.23 -67.68
REMARK 500 LEU B 210 144.88 -170.21
REMARK 500 TRP B 258 -83.41 -148.37
REMARK 500 VAL B 373 -5.30 -56.40
REMARK 500 THR B 375 7.43 59.38
REMARK 500 SER B 376 -169.42 -49.99
REMARK 500 ALA B 384 35.49 -97.60
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 3TO A 501
REMARK 800
REMARK 800 SITE_IDENTIFIER: AC2
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: BINDING SITE FOR RESIDUE TLA A 502
REMARK 800
REMARK 800 SITE_IDENTIFIER: AC3
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: BINDING SITE FOR RESIDUE 3TO B 501
REMARK 800
REMARK 800 SITE_IDENTIFIER: AC4
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: BINDING SITE FOR RESIDUE TLA B 502
REMARK 900
REMARK 900 RELATED ENTRIES
REMARK 900 RELATED ID: 3KMX RELATED DB: PDB
REMARK 900 STRUCTURE OF BACE BOUND TO SCH346572
REMARK 900 RELATED ID: 3KMY RELATED DB: PDB
REMARK 900 STRUCTURE OF BACE BOUND TO SCH12472
DBREF 3KN0 A 53 447 UNP P56817 BACE1_HUMAN 53 447
DBREF 3KN0 B 53 447 UNP P56817 BACE1_HUMAN 53 447
SEQRES 1 A 395 GLU PRO GLY ARG ARG GLY SER PHE VAL GLU MET VAL ASP
SEQRES 2 A 395 ASN LEU ARG GLY LYS SER GLY GLN GLY TYR TYR VAL GLU
SEQRES 3 A 395 MET THR VAL GLY SER PRO PRO GLN THR LEU ASN ILE LEU
SEQRES 4 A 395 VAL ASP THR GLY SER SER ASN PHE ALA VAL GLY ALA ALA
SEQRES 5 A 395 PRO HIS PRO PHE LEU HIS ARG TYR TYR GLN ARG GLN LEU
SEQRES 6 A 395 SER SER THR TYR ARG ASP LEU ARG LYS GLY VAL TYR VAL
SEQRES 7 A 395 PRO TYR THR GLN GLY LYS TRP GLU GLY GLU LEU GLY THR
SEQRES 8 A 395 ASP LEU VAL SER ILE PRO HIS GLY PRO ASN VAL THR VAL
SEQRES 9 A 395 ARG ALA ASN ILE ALA ALA ILE THR GLU SER ASP LYS PHE
SEQRES 10 A 395 PHE ILE ASN GLY SER ASN TRP GLU GLY ILE LEU GLY LEU
SEQRES 11 A 395 ALA TYR ALA GLU ILE ALA ARG PRO ASP ASP SER LEU GLU
SEQRES 12 A 395 PRO PHE PHE ASP SER LEU VAL LYS GLN THR HIS VAL PRO
SEQRES 13 A 395 ASN LEU PHE SER LEU GLN LEU CYS GLY ALA GLY PHE PRO
SEQRES 14 A 395 LEU ASN GLN SER GLU VAL LEU ALA SER VAL GLY GLY SER
SEQRES 15 A 395 MET ILE ILE GLY GLY ILE ASP HIS SER LEU TYR THR GLY
SEQRES 16 A 395 SER LEU TRP TYR THR PRO ILE ARG ARG GLU TRP TYR TYR
SEQRES 17 A 395 GLU VAL ILE ILE VAL ARG VAL GLU ILE ASN GLY GLN ASP
SEQRES 18 A 395 LEU LYS MET ASP CYS LYS GLU TYR ASN TYR ASP LYS SER
SEQRES 19 A 395 ILE VAL ASP SER GLY THR THR ASN LEU ARG LEU PRO LYS
SEQRES 20 A 395 LYS VAL PHE GLU ALA ALA VAL LYS SER ILE LYS ALA ALA
SEQRES 21 A 395 SER SER THR GLU LYS PHE PRO ASP GLY PHE TRP LEU GLY
SEQRES 22 A 395 GLU GLN LEU VAL CYS TRP GLN ALA GLY THR THR PRO TRP
SEQRES 23 A 395 ASN ILE PHE PRO VAL ILE SER LEU TYR LEU MET GLY GLU
SEQRES 24 A 395 VAL THR ASN GLN SER PHE ARG ILE THR ILE LEU PRO GLN
SEQRES 25 A 395 GLN TYR LEU ARG PRO VAL GLU ASP VAL ALA THR SER GLN
SEQRES 26 A 395 ASP ASP CYS TYR LYS PHE ALA ILE SER GLN SER SER THR
SEQRES 27 A 395 GLY THR VAL MET GLY ALA VAL ILE MET GLU GLY PHE TYR
SEQRES 28 A 395 VAL VAL PHE ASP ARG ALA ARG LYS ARG ILE GLY PHE ALA
SEQRES 29 A 395 VAL SER ALA CYS HIS VAL HIS ASP GLU PHE ARG THR ALA
SEQRES 30 A 395 ALA VAL GLU GLY PRO PHE VAL THR LEU ASP MET GLU ASP
SEQRES 31 A 395 CYS GLY TYR ASN ILE
SEQRES 1 B 395 GLU PRO GLY ARG ARG GLY SER PHE VAL GLU MET VAL ASP
SEQRES 2 B 395 ASN LEU ARG GLY LYS SER GLY GLN GLY TYR TYR VAL GLU
SEQRES 3 B 395 MET THR VAL GLY SER PRO PRO GLN THR LEU ASN ILE LEU
SEQRES 4 B 395 VAL ASP THR GLY SER SER ASN PHE ALA VAL GLY ALA ALA
SEQRES 5 B 395 PRO HIS PRO PHE LEU HIS ARG TYR TYR GLN ARG GLN LEU
SEQRES 6 B 395 SER SER THR TYR ARG ASP LEU ARG LYS GLY VAL TYR VAL
SEQRES 7 B 395 PRO TYR THR GLN GLY LYS TRP GLU GLY GLU LEU GLY THR
SEQRES 8 B 395 ASP LEU VAL SER ILE PRO HIS GLY PRO ASN VAL THR VAL
SEQRES 9 B 395 ARG ALA ASN ILE ALA ALA ILE THR GLU SER ASP LYS PHE
SEQRES 10 B 395 PHE ILE ASN GLY SER ASN TRP GLU GLY ILE LEU GLY LEU
SEQRES 11 B 395 ALA TYR ALA GLU ILE ALA ARG PRO ASP ASP SER LEU GLU
SEQRES 12 B 395 PRO PHE PHE ASP SER LEU VAL LYS GLN THR HIS VAL PRO
SEQRES 13 B 395 ASN LEU PHE SER LEU GLN LEU CYS GLY ALA GLY PHE PRO
SEQRES 14 B 395 LEU ASN GLN SER GLU VAL LEU ALA SER VAL GLY GLY SER
SEQRES 15 B 395 MET ILE ILE GLY GLY ILE ASP HIS SER LEU TYR THR GLY
SEQRES 16 B 395 SER LEU TRP TYR THR PRO ILE ARG ARG GLU TRP TYR TYR
SEQRES 17 B 395 GLU VAL ILE ILE VAL ARG VAL GLU ILE ASN GLY GLN ASP
SEQRES 18 B 395 LEU LYS MET ASP CYS LYS GLU TYR ASN TYR ASP LYS SER
SEQRES 19 B 395 ILE VAL ASP SER GLY THR THR ASN LEU ARG LEU PRO LYS
SEQRES 20 B 395 LYS VAL PHE GLU ALA ALA VAL LYS SER ILE LYS ALA ALA
SEQRES 21 B 395 SER SER THR GLU LYS PHE PRO ASP GLY PHE TRP LEU GLY
SEQRES 22 B 395 GLU GLN LEU VAL CYS TRP GLN ALA GLY THR THR PRO TRP
SEQRES 23 B 395 ASN ILE PHE PRO VAL ILE SER LEU TYR LEU MET GLY GLU
SEQRES 24 B 395 VAL THR ASN GLN SER PHE ARG ILE THR ILE LEU PRO GLN
SEQRES 25 B 395 GLN TYR LEU ARG PRO VAL GLU ASP VAL ALA THR SER GLN
SEQRES 26 B 395 ASP ASP CYS TYR LYS PHE ALA ILE SER GLN SER SER THR
SEQRES 27 B 395 GLY THR VAL MET GLY ALA VAL ILE MET GLU GLY PHE TYR
SEQRES 28 B 395 VAL VAL PHE ASP ARG ALA ARG LYS ARG ILE GLY PHE ALA
SEQRES 29 B 395 VAL SER ALA CYS HIS VAL HIS ASP GLU PHE ARG THR ALA
SEQRES 30 B 395 ALA VAL GLU GLY PRO PHE VAL THR LEU ASP MET GLU ASP
SEQRES 31 B 395 CYS GLY TYR ASN ILE
HET 3TO A 501 24
HET TLA A 502 10
HET 3TO B 501 24
HET TLA B 502 10
HETNAM 3TO 3-[2-(3-{[(FURAN-2-YLMETHYL)(METHYL)
HETNAM 2 3TO AMINO]METHYL}PHENYL)ETHYL]PYRIDIN-2-AMINE
HETNAM TLA L(+)-TARTARIC ACID
FORMUL 3 3TO 2(C20 H23 N3 O)
FORMUL 4 TLA 2(C4 H6 O6)
FORMUL 7 HOH *942(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 SER A 225 SER A 230 1 6
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 SER B 225 SER B 230 1 6
HELIX 17 17 ASP B 241 SER B 243 5 3
HELIX 18 18 ASP B 277 TYR B 283 5 7
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 ARG B 408 ARG B 410 5 3
HELIX 25 25 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 ILE A 90 N VAL A 77
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 SER A 166 1 O ILE A 163 N VAL A 101
SHEET 7 A 8 TRP A 137 SER A 147 -1 N GLU A 138 O GLU A 165
SHEET 8 A 8 ARG A 122 VAL A 130 -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 TRP A 137 SER A 147 -1 O SER A 147 N THR A 80
SHEET 4 B 4 ARG A 122 VAL A 130 -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 GLU A 261 VAL A 262 0
SHEET 2 D 5 SER A 286 VAL A 288 -1 O SER A 286 N VAL A 262
SHEET 3 D 5 THR A 392 MET A 394 1 O MET A 394 N ILE A 287
SHEET 4 D 5 LEU A 295 PRO A 298 -1 N ARG A 296 O VAL A 393
SHEET 5 D 5 ILE A 385 SER A 388 1 O SER A 388 N LEU A 297
SHEET 1 E 5 GLN A 272 ASP A 273 0
SHEET 2 E 5 ILE A 264 ILE A 269 -1 N ILE A 269 O GLN A 272
SHEET 3 E 5 ILE A 344 MET A 349 -1 O TYR A 347 N ARG A 266
SHEET 4 E 5 GLN A 355 ILE A 361 -1 O ILE A 361 N ILE A 344
SHEET 5 E 5 ALA A 430 VAL A 436 -1 O GLU A 432 N ARG A 358
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 GLY B 74 N LYS B 70
SHEET 3 G 8 GLN B 86 ASP B 93 -1 O ILE B 90 N VAL B 77
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 ASP B 167 1 O ILE B 163 N VAL B 101
SHEET 7 G 8 GLY B 135 SER B 147 -1 N GLU B 138 O GLU B 165
SHEET 8 G 8 ARG B 122 TYR B 132 -1 N VAL B 128 O GLY B 139
SHEET 1 H 4 LEU B 67 LYS B 70 0
SHEET 2 H 4 GLY B 74 VAL B 81 -1 O GLY B 74 N LYS B 70
SHEET 3 H 4 GLY B 135 SER B 147 -1 O SER B 147 N THR B 80
SHEET 4 H 4 ARG B 122 TYR B 132 -1 N VAL B 128 O GLY B 139
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 GLU B 261 VAL B 262 0
SHEET 2 J 5 SER B 286 VAL B 288 -1 O SER B 286 N VAL B 262
SHEET 3 J 5 THR B 392 MET B 394 1 O MET B 394 N ILE B 287
SHEET 4 J 5 LEU B 295 PRO B 298 -1 N ARG B 296 O VAL B 393
SHEET 5 J 5 ILE B 385 SER B 388 1 O SER B 388 N LEU B 297
SHEET 1 K 5 GLN B 272 ASP B 273 0
SHEET 2 K 5 ILE B 264 ILE B 269 -1 N ILE B 269 O GLN B 272
SHEET 3 K 5 ILE B 344 MET B 349 -1 O TYR B 347 N ARG B 266
SHEET 4 K 5 GLN B 355 ILE B 361 -1 O ILE B 361 N ILE B 344
SHEET 5 K 5 ALA B 430 VAL B 436 -1 O ALA B 430 N THR B 360
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 2.05
SSBOND 2 CYS A 278 CYS A 443 1555 1555 2.03
SSBOND 3 CYS A 330 CYS A 380 1555 1555 2.04
SSBOND 4 CYS B 216 CYS B 420 1555 1555 2.05
SSBOND 5 CYS B 278 CYS B 443 1555 1555 2.04
SSBOND 6 CYS B 330 CYS B 380 1555 1555 2.04
CISPEP 1 SER A 83 PRO A 84 0 -0.47
CISPEP 2 ARG A 189 PRO A 190 0 0.69
CISPEP 3 TYR A 283 ASP A 284 0 11.46
CISPEP 4 GLY A 433 PRO A 434 0 -0.17
CISPEP 5 SER B 83 PRO B 84 0 -0.28
CISPEP 6 ARG B 189 PRO B 190 0 0.40
CISPEP 7 TYR B 283 ASP B 284 0 7.09
CISPEP 8 GLY B 433 PRO B 434 0 -0.12
SITE 1 AC1 11 SER A 71 GLN A 73 GLY A 74 ASP A 93
SITE 2 AC1 11 TYR A 132 ILE A 179 ASP A 289 SER A 290
SITE 3 AC1 11 GLY A 291 THR A 292 THR A 293
SITE 1 AC2 8 ARG A 68 ASN A 89 HIS A 110 ARG A 111
SITE 2 AC2 8 ASN A 175 HOH A 554 HOH A 612 HOH A 627
SITE 1 AC3 13 SER B 71 GLN B 73 GLY B 74 ASP B 93
SITE 2 AC3 13 GLY B 95 TYR B 132 GLN B 134 ILE B 179
SITE 3 AC3 13 ASP B 289 SER B 290 GLY B 291 THR B 292
SITE 4 AC3 13 THR B 293
SITE 1 AC4 8 ARG B 68 ASN B 89 HIS B 110 ARG B 111
SITE 2 AC4 8 ASN B 175 HOH B 507 HOH B 572 HOH B 662
CRYST1 86.448 89.741 131.265 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 0.011568 0.000000 0.000000 0.00000
SCALE2 0.000000 0.011143 0.000000 0.00000
SCALE3 0.000000 0.000000 0.007618 0.00000
(ATOM LINES ARE NOT SHOWN.)
END
