HEADER HYDROLASE/HYDROLASE INHIBITOR 26-MAY-11 3S7L
TITLE PYRAZOLYL AND THIENYL AMINOHYDANTOINS AS POTENT BACE1 INHIBITORS
COMPND MOL_ID: 1;
COMPND 2 MOLECULE: BETA-SECRETASE 1;
COMPND 3 CHAIN: A;
COMPND 4 FRAGMENT: UNP RESIDUES 46-454;
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: 562
KEYWDS ASPARTYL PROTEASE, DISULFIDE BOND, PROTEASE, HYDROLASE-HYDROLASE
KEYWDS 2 INHIBITOR COMPLEX
EXPDTA X-RAY DIFFRACTION
AUTHOR R.CHOPRA,A.OLLAND,K.SVENSON
REVDAT 1 31-AUG-11 3S7L 0
JRNL AUTH M.S.MALAMAS,J.ERDEI,I.GUNAWAN,K.BARNES,Y.HUI,M.JOHNSON,
JRNL AUTH 2 A.ROBICHAUD,P.ZHOU,Y.YAN,W.SOLVIBILE,J.TURNER,K.Y.FAN,
JRNL AUTH 3 R.CHOPRA,J.BARD,M.N.PANGALOS
JRNL TITL NEW PYRAZOLYL AND THIENYL AMINOHYDANTOINS AS POTENT BACE1
JRNL TITL 2 INHIBITORS: EXPLORING THE S2' REGION.
JRNL REF BIOORG.MED.CHEM.LETT. V. 21 5164 2011
JRNL REFN ISSN 0960-894X
JRNL PMID 21835615
JRNL DOI 10.1016/J.BMCL.2011.07.057
REMARK 2
REMARK 2 RESOLUTION. 2.16 ANGSTROMS.
REMARK 3
REMARK 3 REFINEMENT.
REMARK 3 PROGRAM : PHENIX
REMARK 3 AUTHORS : PAUL ADAMS,PAVEL AFONINE,VICENT CHEN,IAN
REMARK 3 : DAVIS,KRESHNA GOPAL,RALF GROSSE-
REMARK 3 : KUNSTLEVE,LI-WEI HUNG,ROBERT IMMORMINO,
REMARK 3 : TOM IOERGER,AIRLIE MCCOY,ERIK MCKEE,NIGEL
REMARK 3 : MORIARTY,REETAL PAI,RANDY READ,JANE
REMARK 3 : RICHARDSON,DAVID RICHARDSON,TOD ROMO,JIM
REMARK 3 : SACCHETTINI,NICHOLAS SAUTER,JACOB SMITH,
REMARK 3 : LAURENT STORONI,TOM TERWILLIGER,PETER
REMARK 3 : ZWART
REMARK 3
REMARK 3 REFINEMENT TARGET : ML
REMARK 3
REMARK 3 DATA USED IN REFINEMENT.
REMARK 3 RESOLUTION RANGE HIGH (ANGSTROMS) : 2.16
REMARK 3 RESOLUTION RANGE LOW (ANGSTROMS) : 19.95
REMARK 3 MIN(FOBS/SIGMA_FOBS) : 0.000
REMARK 3 COMPLETENESS FOR RANGE (%) : 86.1
REMARK 3 NUMBER OF REFLECTIONS : 17190
REMARK 3
REMARK 3 FIT TO DATA USED IN REFINEMENT.
REMARK 3 R VALUE (WORKING + TEST SET) : 0.177
REMARK 3 R VALUE (WORKING SET) : 0.174
REMARK 3 FREE R VALUE : 0.227
REMARK 3 FREE R VALUE TEST SET SIZE (%) : 5.190
REMARK 3 FREE R VALUE TEST SET COUNT : 892
REMARK 3
REMARK 3 FIT TO DATA USED IN REFINEMENT (IN BINS).
REMARK 3 BIN RESOLUTION RANGE COMPL. NWORK NFREE RWORK RFREE
REMARK 3 1 19.9513 - 3.9205 1.00 3214 160 0.1577 0.1960
REMARK 3 2 3.9205 - 3.1157 1.00 3145 183 0.1673 0.2141
REMARK 3 3 3.1157 - 2.7230 0.99 3132 162 0.1801 0.2279
REMARK 3 4 2.7230 - 2.4745 0.98 3057 182 0.1828 0.2664
REMARK 3 5 2.4745 - 2.2974 0.89 2770 147 0.1956 0.2630
REMARK 3 6 2.2974 - 2.1621 0.31 980 58 0.2181 0.3165
REMARK 3
REMARK 3 BULK SOLVENT MODELLING.
REMARK 3 METHOD USED : FLAT BULK SOLVENT MODEL
REMARK 3 SOLVENT RADIUS : 1.11
REMARK 3 SHRINKAGE RADIUS : 0.90
REMARK 3 K_SOL : 0.34
REMARK 3 B_SOL : 36.24
REMARK 3
REMARK 3 ERROR ESTIMATES.
REMARK 3 COORDINATE ERROR (MAXIMUM-LIKELIHOOD BASED) : 0.020
REMARK 3 PHASE ERROR (DEGREES, MAXIMUM-LIKELIHOOD BASED) : 25.130
REMARK 3
REMARK 3 B VALUES.
REMARK 3 FROM WILSON PLOT (A**2) : NULL
REMARK 3 MEAN B VALUE (OVERALL, A**2) : 33.04
REMARK 3 OVERALL ANISOTROPIC B VALUE.
REMARK 3 B11 (A**2) : -3.87850
REMARK 3 B22 (A**2) : -6.05200
REMARK 3 B33 (A**2) : 8.26620
REMARK 3 B12 (A**2) : -0.00000
REMARK 3 B13 (A**2) : -7.77700
REMARK 3 B23 (A**2) : 0.00000
REMARK 3
REMARK 3 TWINNING INFORMATION.
REMARK 3 FRACTION: NULL
REMARK 3 OPERATOR: NULL
REMARK 3
REMARK 3 DEVIATIONS FROM IDEAL VALUES.
REMARK 3 RMSD COUNT
REMARK 3 BOND : 0.011 2994
REMARK 3 ANGLE : 1.266 4067
REMARK 3 CHIRALITY : 0.069 443
REMARK 3 PLANARITY : 0.005 520
REMARK 3 DIHEDRAL : 17.251 1053
REMARK 3
REMARK 3 TLS DETAILS
REMARK 3 NUMBER OF TLS GROUPS : NULL
REMARK 3
REMARK 3 NCS DETAILS
REMARK 3 NUMBER OF NCS GROUPS : NULL
REMARK 3
REMARK 3 OTHER REFINEMENT REMARKS: NULL
REMARK 4
REMARK 4 3S7L COMPLIES WITH FORMAT V. 3.30, 13-JUL-11
REMARK 100
REMARK 100 THIS ENTRY HAS BEEN PROCESSED BY RCSB ON 06-JUN-11.
REMARK 100 THE RCSB ID CODE IS RCSB065861.
REMARK 200
REMARK 200 EXPERIMENTAL DETAILS
REMARK 200 EXPERIMENT TYPE : X-RAY DIFFRACTION
REMARK 200 DATE OF DATA COLLECTION : 20-JAN-04
REMARK 200 TEMPERATURE (KELVIN) : 100
REMARK 200 PH : 5.4
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 RU300
REMARK 200 MONOCHROMATIC OR LAUE (M/L) : M
REMARK 200 WAVELENGTH OR RANGE (A) : 1.54
REMARK 200 MONOCHROMATOR : NULL
REMARK 200 OPTICS : NULL
REMARK 200
REMARK 200 DETECTOR TYPE : CCD
REMARK 200 DETECTOR MANUFACTURER : BRUKER SMART 6000
REMARK 200 INTENSITY-INTEGRATION SOFTWARE : HKL-2000
REMARK 200 DATA SCALING SOFTWARE : HKL-2000
REMARK 200
REMARK 200 NUMBER OF UNIQUE REFLECTIONS : 17193
REMARK 200 RESOLUTION RANGE HIGH (A) : 2.162
REMARK 200 RESOLUTION RANGE LOW (A) : 20.000
REMARK 200 REJECTION CRITERIA (SIGMA(I)) : 1.500
REMARK 200
REMARK 200 OVERALL.
REMARK 200 COMPLETENESS FOR RANGE (%) : 87.0
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) : 2.16
REMARK 200 HIGHEST RESOLUTION SHELL, RANGE LOW (A) : 2.24
REMARK 200 COMPLETENESS FOR SHELL (%) : 17.0
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: PHENIX
REMARK 200 STARTING MODEL: NULL
REMARK 200
REMARK 200 REMARK: NULL
REMARK 280
REMARK 280 CRYSTAL
REMARK 280 SOLVENT CONTENT, VS (%): 39.81
REMARK 280 MATTHEWS COEFFICIENT, VM (ANGSTROMS**3/DA): 2.04
REMARK 280
REMARK 280 CRYSTALLIZATION CONDITIONS: 10-15% PEG 3350, 100 MM NAACETATE PH
REMARK 280 5.4, VAPOR DIFFUSION, HANGING DROP, TEMPERATURE 291K
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 36.41750
REMARK 290 SMTRY2 3 0.000000 1.000000 0.000000 51.87450
REMARK 290 SMTRY3 3 0.000000 0.000000 1.000000 0.00000
REMARK 290 SMTRY1 4 -1.000000 0.000000 0.000000 36.41750
REMARK 290 SMTRY2 4 0.000000 1.000000 0.000000 51.87450
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 GLU A 47
REMARK 465 THR A 48
REMARK 465 ASP A 49
REMARK 465 GLU A 50
REMARK 465 GLU A 51
REMARK 465 PRO A 52
REMARK 465 GLU A 53
REMARK 465 GLU A 54
REMARK 465 PRO A 55
REMARK 465 GLY A 56
REMARK 465 ARG A 57
REMARK 465 ARG A 58
REMARK 465 GLY A 59
REMARK 465 GLY A 220
REMARK 465 PHE A 221
REMARK 465 PRO A 222
REMARK 465 LEU A 223
REMARK 465 ASN A 224
REMARK 465 GLN A 225
REMARK 465 SER A 226
REMARK 465 GLU A 372
REMARK 465 ASP A 373
REMARK 465 VAL A 374
REMARK 465 ALA A 375
REMARK 465 THR A 376
REMARK 465 SER A 377
REMARK 465 GLN A 378
REMARK 465 ASP A 379
REMARK 465 ASP A 440
REMARK 465 MET A 441
REMARK 465 GLU A 442
REMARK 465 ASN A 447
REMARK 465 ILE A 448
REMARK 465 PRO A 449
REMARK 465 GLN A 450
REMARK 465 THR A 451
REMARK 465 ASP A 452
REMARK 465 GLU A 453
REMARK 465 SER A 454
REMARK 465 THR 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 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 318 CG CD CE NZ
REMARK 470 LEU A 329 CG CD1 CD2
REMARK 470 TYR A 446 CG CD1 CD2 CE1 CE2 CZ OH
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 VAL A 131 77.67 -118.30
REMARK 500 LYS A 137 141.51 -175.07
REMARK 500 TRP A 259 -90.16 -143.53
REMARK 500 GLU A 317 124.81 79.99
REMARK 500 ALA A 334 93.62 56.48
REMARK 500 ALA A 385 35.47 -95.39
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 591 A 1
REMARK 900
REMARK 900 RELATED ENTRIES
REMARK 900 RELATED ID: 3S7M RELATED DB: PDB
DBREF 3S7L A 47 455 UNP P56817 BACE1_HUMAN 46 454
SEQADV 3S7L HIS A 456 UNP P56817 EXPRESSION TAG
SEQADV 3S7L HIS A 457 UNP P56817 EXPRESSION TAG
SEQADV 3S7L HIS A 458 UNP P56817 EXPRESSION TAG
SEQADV 3S7L HIS A 459 UNP P56817 EXPRESSION TAG
SEQADV 3S7L HIS A 460 UNP P56817 EXPRESSION TAG
SEQADV 3S7L HIS A 461 UNP P56817 EXPRESSION TAG
SEQRES 1 A 415 GLU THR ASP GLU GLU PRO GLU GLU PRO GLY ARG ARG GLY
SEQRES 2 A 415 SER PHE VAL GLU MET VAL ASP ASN LEU ARG GLY LYS SER
SEQRES 3 A 415 GLY GLN GLY TYR TYR VAL GLU MET THR VAL GLY SER PRO
SEQRES 4 A 415 PRO GLN THR LEU ASN ILE LEU VAL ASP THR GLY SER SER
SEQRES 5 A 415 ASN PHE ALA VAL GLY ALA ALA PRO HIS PRO PHE LEU HIS
SEQRES 6 A 415 ARG TYR TYR GLN ARG GLN LEU SER SER THR TYR ARG ASP
SEQRES 7 A 415 LEU ARG LYS GLY VAL TYR VAL PRO TYR THR GLN GLY LYS
SEQRES 8 A 415 TRP GLU GLY GLU LEU GLY THR ASP LEU VAL SER ILE PRO
SEQRES 9 A 415 HIS GLY PRO ASN VAL THR VAL ARG ALA ASN ILE ALA ALA
SEQRES 10 A 415 ILE THR GLU SER ASP LYS PHE PHE ILE ASN GLY SER ASN
SEQRES 11 A 415 TRP GLU GLY ILE LEU GLY LEU ALA TYR ALA GLU ILE ALA
SEQRES 12 A 415 ARG PRO ASP ASP SER LEU GLU PRO PHE PHE ASP SER LEU
SEQRES 13 A 415 VAL LYS GLN THR HIS VAL PRO ASN LEU PHE SER LEU GLN
SEQRES 14 A 415 LEU CYS GLY ALA GLY PHE PRO LEU ASN GLN SER GLU VAL
SEQRES 15 A 415 LEU ALA SER VAL GLY GLY SER MET ILE ILE GLY GLY ILE
SEQRES 16 A 415 ASP HIS SER LEU TYR THR GLY SER LEU TRP TYR THR PRO
SEQRES 17 A 415 ILE ARG ARG GLU TRP TYR TYR GLU VAL ILE ILE VAL ARG
SEQRES 18 A 415 VAL GLU ILE ASN GLY GLN ASP LEU LYS MET ASP CYS LYS
SEQRES 19 A 415 GLU TYR ASN TYR ASP LYS SER ILE VAL ASP SER GLY THR
SEQRES 20 A 415 THR ASN LEU ARG LEU PRO LYS LYS VAL PHE GLU ALA ALA
SEQRES 21 A 415 VAL LYS SER ILE LYS ALA ALA SER SER THR GLU LYS PHE
SEQRES 22 A 415 PRO ASP GLY PHE TRP LEU GLY GLU GLN LEU VAL CYS TRP
SEQRES 23 A 415 GLN ALA GLY THR THR PRO TRP ASN ILE PHE PRO VAL ILE
SEQRES 24 A 415 SER LEU TYR LEU MET GLY GLU VAL THR ASN GLN SER PHE
SEQRES 25 A 415 ARG ILE THR ILE LEU PRO GLN GLN TYR LEU ARG PRO VAL
SEQRES 26 A 415 GLU ASP VAL ALA THR SER GLN ASP ASP CYS TYR LYS PHE
SEQRES 27 A 415 ALA ILE SER GLN SER SER THR GLY THR VAL MET GLY ALA
SEQRES 28 A 415 VAL ILE MET GLU GLY PHE TYR VAL VAL PHE ASP ARG ALA
SEQRES 29 A 415 ARG LYS ARG ILE GLY PHE ALA VAL SER ALA CYS HIS VAL
SEQRES 30 A 415 HIS ASP GLU PHE ARG THR ALA ALA VAL GLU GLY PRO PHE
SEQRES 31 A 415 VAL THR LEU ASP MET GLU ASP CYS GLY TYR ASN ILE PRO
SEQRES 32 A 415 GLN THR ASP GLU SER THR HIS HIS HIS HIS HIS HIS
HET 591 A 1 27
HETNAM 591 (5S)-2-AMINO-5-(1-ETHYL-1H-PYRAZOL-4-YL)-3-METHYL-5-[3-
HETNAM 2 591 (PYRIMIDIN-5-YL)PHENYL]-3,5-DIHYDRO-4H-IMIDAZOL-4-ONE
HETSYN 591 WAY-256591
FORMUL 2 591 C19 H19 N7 O
FORMUL 3 HOH *148(H2 O)
HELIX 1 1 SER A 60 VAL A 65 1 6
HELIX 2 2 GLN A 115 SER A 119 5 5
HELIX 3 3 TYR A 185 ALA A 189 5 5
HELIX 4 4 PRO A 197 THR A 206 1 10
HELIX 5 5 ASP A 242 SER A 244 5 3
HELIX 6 6 ASP A 278 TYR A 282 5 5
HELIX 7 7 LYS A 300 SER A 314 1 15
HELIX 8 8 PRO A 320 LEU A 325 1 6
HELIX 9 9 PRO A 338 PHE A 342 5 5
HELIX 10 10 LEU A 363 TYR A 367 1 5
HELIX 11 11 GLY A 396 GLU A 401 1 6
HELIX 12 12 ARG A 409 ARG A 411 5 3
SHEET 1 A 9 ARG A 123 PRO A 132 0
SHEET 2 A 9 LYS A 137 SER A 148 -1 O TRP A 138 N VAL A 131
SHEET 3 A 9 TYR A 76 VAL A 82 -1 N THR A 81 O SER A 148
SHEET 4 A 9 LEU A 68 LYS A 71 -1 N ARG A 69 O TYR A 77
SHEET 5 A 9 SER A 231 ILE A 238 -1 O VAL A 232 N GLY A 70
SHEET 6 A 9 PHE A 212 GLY A 218 -1 N GLN A 215 O SER A 235
SHEET 7 A 9 PHE A 403 ASP A 408 -1 O PHE A 407 N PHE A 212
SHEET 8 A 9 ARG A 413 SER A 419 -1 O ALA A 417 N TYR A 404
SHEET 9 A 9 TYR A 246 PRO A 254 -1 N THR A 253 O ILE A 414
SHEET 1 B13 ARG A 123 PRO A 132 0
SHEET 2 B13 LYS A 137 SER A 148 -1 O TRP A 138 N VAL A 131
SHEET 3 B13 VAL A 157 ASP A 168 -1 O VAL A 157 N VAL A 147
SHEET 4 B13 PHE A 100 GLY A 103 1 N PHE A 100 O ALA A 162
SHEET 5 B13 GLY A 179 GLY A 182 -1 O ILE A 180 N ALA A 101
SHEET 6 B13 GLN A 87 ASP A 94 1 N LEU A 92 O LEU A 181
SHEET 7 B13 TYR A 76 VAL A 82 -1 N VAL A 78 O ILE A 91
SHEET 8 B13 LEU A 68 LYS A 71 -1 N ARG A 69 O TYR A 77
SHEET 9 B13 SER A 231 ILE A 238 -1 O VAL A 232 N GLY A 70
SHEET 10 B13 PHE A 212 GLY A 218 -1 N GLN A 215 O SER A 235
SHEET 11 B13 PHE A 403 ASP A 408 -1 O PHE A 407 N PHE A 212
SHEET 12 B13 ARG A 413 SER A 419 -1 O ALA A 417 N TYR A 404
SHEET 13 B13 TYR A 246 PRO A 254 -1 N THR A 253 O ILE A 414
SHEET 1 C 5 GLU A 262 VAL A 263 0
SHEET 2 C 5 SER A 287 VAL A 289 -1 O SER A 287 N VAL A 263
SHEET 3 C 5 THR A 393 MET A 395 1 O MET A 395 N ILE A 288
SHEET 4 C 5 LEU A 296 PRO A 299 -1 N ARG A 297 O VAL A 394
SHEET 5 C 5 ILE A 386 SER A 389 1 O SER A 387 N LEU A 298
SHEET 1 D 5 GLN A 273 ASP A 274 0
SHEET 2 D 5 ILE A 265 ILE A 270 -1 N ILE A 270 O GLN A 273
SHEET 3 D 5 ILE A 345 MET A 350 -1 O TYR A 348 N ARG A 267
SHEET 4 D 5 GLN A 356 ILE A 362 -1 O ILE A 360 N LEU A 347
SHEET 5 D 5 ALA A 431 VAL A 437 -1 O GLU A 433 N ARG A 359
SHEET 1 E 3 VAL A 330 CYS A 331 0
SHEET 2 E 3 CYS A 381 PHE A 384 -1 O TYR A 382 N VAL A 330
SHEET 3 E 3 LEU A 368 PRO A 370 -1 N ARG A 369 O LYS A 383
SSBOND 1 CYS A 217 CYS A 421 1555 1555 2.03
SSBOND 2 CYS A 279 CYS A 444 1555 1555 2.05
SSBOND 3 CYS A 331 CYS A 381 1555 1555 2.04
CISPEP 1 SER A 84 PRO A 85 0 -2.75
CISPEP 2 ARG A 190 PRO A 191 0 2.80
CISPEP 3 TYR A 284 ASP A 285 0 4.85
CISPEP 4 GLY A 434 PRO A 435 0 1.47
SITE 1 AC1 15 HOH A 27 HOH A 39 GLY A 73 GLN A 74
SITE 2 AC1 15 GLY A 75 ASP A 94 GLY A 96 SER A 97
SITE 3 AC1 15 TYR A 133 GLN A 135 ILE A 172 ASP A 290
SITE 4 AC1 15 GLY A 292 THR A 293 HOH A 565
CRYST1 72.835 103.749 50.411 90.00 94.82 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 0.013730 0.000000 0.001158 0.00000
SCALE2 0.000000 0.009639 0.000000 0.00000
SCALE3 0.000000 0.000000 0.019907 0.00000
(ATOM LINES ARE NOT SHOWN.)
END
