HEADER IMMUNE SYSTEM 01-MAY-13 4KI5
TITLE CYSTAL STRUCTURE OF HUMAN FACTOR VIII C2 DOMAIN IN A TERNARY COMPLEX
TITLE 2 WITH MURINE INHBITORY ANTIBODIES 3E6 AND G99
COMPND MOL_ID: 1;
COMPND 2 MOLECULE: MURINE MONOCLONAL 3E6 FAB HEAVY CHAIN;
COMPND 3 CHAIN: C;
COMPND 4 MOL_ID: 2;
COMPND 5 MOLECULE: MURINE MONOCLONAL 3E6 FAB LIGHT CHAIN;
COMPND 6 CHAIN: D;
COMPND 7 MOL_ID: 3;
COMPND 8 MOLECULE: MURINE MONOCLONAL G99 FAB HEAVY CHAIN;
COMPND 9 CHAIN: E;
COMPND 10 MOL_ID: 4;
COMPND 11 MOLECULE: MURINE MONOCLONAL G99 FAB LIGHT CHAIN;
COMPND 12 CHAIN: F;
COMPND 13 MOL_ID: 5;
COMPND 14 MOLECULE: COAGULATION FACTOR VIII;
COMPND 15 CHAIN: M;
COMPND 16 FRAGMENT: C2 DOMAIN;
COMPND 17 SYNONYM: ANTIHEMOPHILIC FACTOR, AHF, PROCOAGULANT COMPONENT, FACTOR
COMPND 18 VIIIA HEAVY CHAIN, 200 KDA ISOFORM, FACTOR VIIIA HEAVY CHAIN, 92 KDA
COMPND 19 ISOFORM, FACTOR VIII B CHAIN, FACTOR VIIIA LIGHT CHAIN;
COMPND 20 ENGINEERED: YES
SOURCE MOL_ID: 1;
SOURCE 2 ORGANISM_SCIENTIFIC: MUS MUSCULUS;
SOURCE 3 ORGANISM_TAXID: 10090;
SOURCE 4 MOL_ID: 2;
SOURCE 5 ORGANISM_SCIENTIFIC: MUS MUSCULUS;
SOURCE 6 ORGANISM_TAXID: 10090;
SOURCE 7 MOL_ID: 3;
SOURCE 8 ORGANISM_SCIENTIFIC: MUS MUSCULUS;
SOURCE 9 ORGANISM_TAXID: 10090;
SOURCE 10 MOL_ID: 4;
SOURCE 11 ORGANISM_SCIENTIFIC: MUS MUSCULUS;
SOURCE 12 ORGANISM_TAXID: 10090;
SOURCE 13 MOL_ID: 5;
SOURCE 14 ORGANISM_SCIENTIFIC: HOMO SAPIENS;
SOURCE 15 ORGANISM_COMMON: HUMAN;
SOURCE 16 ORGANISM_TAXID: 9606;
SOURCE 17 GENE: F8, F8C;
SOURCE 18 EXPRESSION_SYSTEM: ESCHERICHIA COLI;
SOURCE 19 EXPRESSION_SYSTEM_TAXID: 562
KEYWDS IMMUNOGLOBULIN FOLD, DISCOIDIN FOLD, ANTIBODY, BLOOD COAGULATION
KEYWDS 2 FACTOR, ANTIGEN BINDING, BLOOD PLASMA, IMMUNE SYSTEM
EXPDTA X-RAY DIFFRACTION
AUTHOR J.D.WALTER,S.L.MEEKS,J.F.HEALEY,P.LOLLAR,P.C.SPIEGEL
REVDAT 1 15-JAN-14 4KI5 0
JRNL AUTH J.D.WALTER,R.A.WERTHER,C.M.BRISON,R.K.CRAGERUD,J.F.HEALEY,
JRNL AUTH 2 S.L.MEEKS,P.LOLLAR,P.C.SPIEGEL
JRNL TITL STRUCTURE OF THE FACTOR VIII C2 DOMAIN IN A TERNARY COMPLEX
JRNL TITL 2 WITH 2 INHIBITOR ANTIBODIES REVEALS CLASSICAL AND
JRNL TITL 3 NONCLASSICAL EPITOPES.
JRNL REF BLOOD V. 122 4270 2013
JRNL REFN ISSN 0006-4971
JRNL PMID 24085769
JRNL DOI 10.1182/BLOOD-2013-08-519124
REMARK 2
REMARK 2 RESOLUTION. 2.47 ANGSTROMS.
REMARK 3
REMARK 3 REFINEMENT.
REMARK 3 PROGRAM : PHENIX (PHENIX.REFINE: 1.8_1069)
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) : 2.47
REMARK 3 RESOLUTION RANGE LOW (ANGSTROMS) : 56.43
REMARK 3 MIN(FOBS/SIGMA_FOBS) : 0.000
REMARK 3 COMPLETENESS FOR RANGE (%) : 99.8
REMARK 3 NUMBER OF REFLECTIONS : 39480
REMARK 3
REMARK 3 FIT TO DATA USED IN REFINEMENT.
REMARK 3 R VALUE (WORKING + TEST SET) : 0.190
REMARK 3 R VALUE (WORKING SET) : 0.188
REMARK 3 FREE R VALUE : 0.238
REMARK 3 FREE R VALUE TEST SET SIZE (%) : 5.060
REMARK 3 FREE R VALUE TEST SET COUNT : 1998
REMARK 3
REMARK 3 FIT TO DATA USED IN REFINEMENT (IN BINS).
REMARK 3 BIN RESOLUTION RANGE COMPL. NWORK NFREE RWORK RFREE
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 : NULL
REMARK 3 B_SOL : NULL
REMARK 3
REMARK 3 ERROR ESTIMATES.
REMARK 3 COORDINATE ERROR (MAXIMUM-LIKELIHOOD BASED) : 0.260
REMARK 3 PHASE ERROR (DEGREES, MAXIMUM-LIKELIHOOD BASED) : 23.950
REMARK 3
REMARK 3 B VALUES.
REMARK 3 FROM WILSON PLOT (A**2) : NULL
REMARK 3 MEAN B VALUE (OVERALL, A**2) : 51.13
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 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 : NULL NULL
REMARK 3 ANGLE : NULL NULL
REMARK 3 CHIRALITY : NULL NULL
REMARK 3 PLANARITY : NULL NULL
REMARK 3 DIHEDRAL : NULL NULL
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 4KI5 COMPLIES WITH FORMAT V. 3.30, 13-JUL-11
REMARK 100
REMARK 100 THIS ENTRY HAS BEEN PROCESSED BY RCSB ON 03-MAY-13.
REMARK 100 THE RCSB ID CODE IS RCSB079368.
REMARK 200
REMARK 200 EXPERIMENTAL DETAILS
REMARK 200 EXPERIMENT TYPE : X-RAY DIFFRACTION
REMARK 200 DATE OF DATA COLLECTION : 12-JUL-12
REMARK 200 TEMPERATURE (KELVIN) : 100
REMARK 200 PH : 7.5
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 RU200
REMARK 200 MONOCHROMATIC OR LAUE (M/L) : M
REMARK 200 WAVELENGTH OR RANGE (A) : 1.54187
REMARK 200 MONOCHROMATOR : NULL
REMARK 200 OPTICS : NULL
REMARK 200
REMARK 200 DETECTOR TYPE : AREA DETECTOR
REMARK 200 DETECTOR MANUFACTURER : RIGAKU RAXIS IV++
REMARK 200 INTENSITY-INTEGRATION SOFTWARE : MOSFLM
REMARK 200 DATA SCALING SOFTWARE : SCALA
REMARK 200
REMARK 200 NUMBER OF UNIQUE REFLECTIONS : 39550
REMARK 200 RESOLUTION RANGE HIGH (A) : 2.470
REMARK 200 RESOLUTION RANGE LOW (A) : 56.428
REMARK 200 REJECTION CRITERIA (SIGMA(I)) : 0.000
REMARK 200
REMARK 200 OVERALL.
REMARK 200 COMPLETENESS FOR RANGE (%) : 99.9
REMARK 200 DATA REDUNDANCY : 14.000
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) : 2.47
REMARK 200 HIGHEST RESOLUTION SHELL, RANGE LOW (A) : 2.61
REMARK 200 COMPLETENESS FOR SHELL (%) : 99.7
REMARK 200 DATA REDUNDANCY IN SHELL : 13.90
REMARK 200 R MERGE FOR SHELL (I) : 0.84000
REMARK 200 R SYM FOR SHELL (I) : 0.84000
REMARK 200 <I/SIGMA(I)> FOR SHELL : 0.900
REMARK 200
REMARK 200 DIFFRACTION PROTOCOL: SINGLE WAVELENGTH
REMARK 200 METHOD USED TO DETERMINE THE STRUCTURE: MOLECULAR REPLACEMENT
REMARK 200 SOFTWARE USED: PHASER
REMARK 200 STARTING MODEL: NULL
REMARK 200
REMARK 200 REMARK: NULL
REMARK 280
REMARK 280 CRYSTAL
REMARK 280 SOLVENT CONTENT, VS (%): 47.16
REMARK 280 MATTHEWS COEFFICIENT, VM (ANGSTROMS**3/DA): 2.33
REMARK 280
REMARK 280 CRYSTALLIZATION CONDITIONS: 28% PEG-1000, 0.15 M SODIUM ACETATE,
REMARK 280 0.025 M TRIS-HCL, 0.05 M NACL, 0.15 M AMMONIUM NITRATE, PH 7.5,
REMARK 280 VAPOR DIFFUSION, HANGING DROP, TEMPERATURE 293K
REMARK 290
REMARK 290 CRYSTALLOGRAPHIC SYMMETRY
REMARK 290 SYMMETRY OPERATORS FOR SPACE GROUP: P 2 21 21
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,Y+1/2,-Z+1/2
REMARK 290 4555 -X,-Y+1/2,Z+1/2
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 0.00000
REMARK 290 SMTRY2 3 0.000000 1.000000 0.000000 35.58000
REMARK 290 SMTRY3 3 0.000000 0.000000 -1.000000 138.92500
REMARK 290 SMTRY1 4 -1.000000 0.000000 0.000000 0.00000
REMARK 290 SMTRY2 4 0.000000 -1.000000 0.000000 35.58000
REMARK 290 SMTRY3 4 0.000000 0.000000 1.000000 138.92500
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: PENTAMERIC
REMARK 350 APPLY THE FOLLOWING TO CHAINS: C, D, E, F, M
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 GLN C 1
REMARK 465 LYS D 198
REMARK 465 THR D 199
REMARK 465 SER F 77
REMARK 465 LYS F 199
REMARK 465 THR F 200
REMARK 465 SER F 201
REMARK 465 THR F 202
REMARK 465 MET M 2150
REMARK 465 GLY M 2151
REMARK 465 SER M 2152
REMARK 465 SER M 2153
REMARK 465 HIS M 2154
REMARK 465 HIS M 2155
REMARK 465 HIS M 2156
REMARK 465 HIS M 2157
REMARK 465 HIS M 2158
REMARK 465 HIS M 2159
REMARK 465 SER M 2160
REMARK 465 SER M 2161
REMARK 465 GLY M 2162
REMARK 465 LEU M 2163
REMARK 465 VAL M 2164
REMARK 465 PRO M 2165
REMARK 465 ARG M 2166
REMARK 465 GLY M 2167
REMARK 465 SER M 2168
REMARK 465 HIS M 2169
REMARK 465 MET M 2170
REMARK 465 LEU M 2171
REMARK 465 ASN M 2172
REMARK 465 SER M 2173
REMARK 465 ALA M 2328
REMARK 465 GLN M 2329
REMARK 465 ASP M 2330
REMARK 465 LEU M 2331
REMARK 465 TYR M 2332
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 SER C 7 -171.77 -68.67
REMARK 500 PRO C 9 154.35 -46.67
REMARK 500 SER C 71 -169.50 -127.56
REMARK 500 ALA C 92 -176.19 -174.83
REMARK 500 ASP C 100 82.32 -160.15
REMARK 500 THR C 135 72.79 -114.69
REMARK 500 THR D 50 -46.10 70.03
REMARK 500 TRP D 90 48.02 -147.99
REMARK 500 LYS D 141 76.92 -69.41
REMARK 500 ASP D 142 23.67 -143.50
REMARK 500 SER E 85 72.04 44.07
REMARK 500 THR E 97 -158.86 -151.67
REMARK 500 CYS E 137 19.05 59.88
REMARK 500 SER F 9 -36.86 74.77
REMARK 500 ALA F 51 -47.66 75.72
REMARK 500 SER F 52 -0.97 -144.62
REMARK 500 SER F 65 -155.51 -149.02
REMARK 500 ARG F 66 131.01 170.42
REMARK 500 SER F 69 47.73 -107.62
REMARK 500 LYS F 169 54.71 -116.07
REMARK 500 ASP F 170 -31.87 -177.02
REMARK 500 ALA M2208 38.48 -88.36
REMARK 500 LYS M2236 137.61 -176.77
REMARK 500 LEU M2251 -124.11 53.46
REMARK 500 HIS M2315 -73.25 70.18
REMARK 500 CYS M2326 -168.77 -167.35
REMARK 500
REMARK 500 REMARK: NULL
DBREF 4KI5 M 2171 2332 UNP P00451 FA8_HUMAN 2190 2351
DBREF 4KI5 C 1 219 PDB 4KI5 4KI5 1 219
DBREF 4KI5 D 1 213 PDB 4KI5 4KI5 1 213
DBREF 4KI5 E 1 224 PDB 4KI5 4KI5 1 224
DBREF 4KI5 F 1 214 PDB 4KI5 4KI5 1 214
SEQADV 4KI5 MET M 2150 UNP P00451 EXPRESSION TAG
SEQADV 4KI5 GLY M 2151 UNP P00451 EXPRESSION TAG
SEQADV 4KI5 SER M 2152 UNP P00451 EXPRESSION TAG
SEQADV 4KI5 SER M 2153 UNP P00451 EXPRESSION TAG
SEQADV 4KI5 HIS M 2154 UNP P00451 EXPRESSION TAG
SEQADV 4KI5 HIS M 2155 UNP P00451 EXPRESSION TAG
SEQADV 4KI5 HIS M 2156 UNP P00451 EXPRESSION TAG
SEQADV 4KI5 HIS M 2157 UNP P00451 EXPRESSION TAG
SEQADV 4KI5 HIS M 2158 UNP P00451 EXPRESSION TAG
SEQADV 4KI5 HIS M 2159 UNP P00451 EXPRESSION TAG
SEQADV 4KI5 SER M 2160 UNP P00451 EXPRESSION TAG
SEQADV 4KI5 SER M 2161 UNP P00451 EXPRESSION TAG
SEQADV 4KI5 GLY M 2162 UNP P00451 EXPRESSION TAG
SEQADV 4KI5 LEU M 2163 UNP P00451 EXPRESSION TAG
SEQADV 4KI5 VAL M 2164 UNP P00451 EXPRESSION TAG
SEQADV 4KI5 PRO M 2165 UNP P00451 EXPRESSION TAG
SEQADV 4KI5 ARG M 2166 UNP P00451 EXPRESSION TAG
SEQADV 4KI5 GLY M 2167 UNP P00451 EXPRESSION TAG
SEQADV 4KI5 SER M 2168 UNP P00451 EXPRESSION TAG
SEQADV 4KI5 HIS M 2169 UNP P00451 EXPRESSION TAG
SEQADV 4KI5 MET M 2170 UNP P00451 EXPRESSION TAG
SEQRES 1 C 219 GLN ILE GLN LEU VAL GLN SER GLY PRO GLU LEU LYS LYS
SEQRES 2 C 219 PRO GLY LYS THR VAL LYS ILE SER CYS LYS ALA SER ASP
SEQRES 3 C 219 TYR THR PHE THR ASP TYR SER LEU HIS TRP VAL LYS GLN
SEQRES 4 C 219 ALA PRO GLY LYS GLY LEU LYS TRP MET GLY TRP ILE ASN
SEQRES 5 C 219 THR GLU THR GLY ASP PRO ALA TYR ALA ASP ASP PHE LYS
SEQRES 6 C 219 GLY ARG PHE ALA PHE SER LEU GLU THR SER VAL ARG THR
SEQRES 7 C 219 ALA TYR LEU GLN ILE ASN ASN LEU LYS ASN GLU ASP THR
SEQRES 8 C 219 ALA ILE TYR PHE CYS ALA ARG GLU ASP ASP GLY LEU ALA
SEQRES 9 C 219 SER TRP GLY GLN GLY THR THR LEU THR VAL SER SER ALA
SEQRES 10 C 219 LYS THR THR ALA PRO SER VAL TYR PRO LEU ALA PRO VAL
SEQRES 11 C 219 CYS GLY ASP THR THR GLY SER SER VAL THR LEU GLY CYS
SEQRES 12 C 219 LEU VAL LYS GLY TYR PHE PRO GLU PRO VAL THR LEU THR
SEQRES 13 C 219 TRP ASN SER GLY SER LEU SER SER GLY VAL HIS THR PHE
SEQRES 14 C 219 PRO ALA VAL LEU GLN SER ASP LEU TYR THR LEU SER SER
SEQRES 15 C 219 SER VAL THR VAL THR SER SER THR TRP PRO SER GLN SER
SEQRES 16 C 219 ILE THR CYS ASN VAL ALA HIS PRO ALA SER SER THR LYS
SEQRES 17 C 219 VAL ASP LYS LYS ILE GLU PRO ARG GLY PRO ALA
SEQRES 1 D 213 GLN ILE VAL LEU THR GLN SER PRO ALA ILE MET SER ALA
SEQRES 2 D 213 SER PRO GLY GLU LYS VAL THR MET THR CYS SER ALA SER
SEQRES 3 D 213 SER THR VAL SER TYR MET TYR TRP TYR GLN GLN LYS PRO
SEQRES 4 D 213 GLY SER SER PRO ARG PHE LEU ILE SER ASP THR SER ASN
SEQRES 5 D 213 LEU ALA SER GLY VAL PRO VAL ARG PHE SER GLY SER GLY
SEQRES 6 D 213 SER GLY THR SER TYR SER LEU THR ILE SER ARG ILE GLU
SEQRES 7 D 213 ALA GLU ASP ALA ALA THR TYR TYR CYS GLN HIS TRP SER
SEQRES 8 D 213 SER TYR PRO LEU THR PHE GLY GLY GLY THR LYS LEU GLU
SEQRES 9 D 213 LEU LYS ARG ALA ASP ALA ALA PRO THR VAL SER ILE PHE
SEQRES 10 D 213 PRO PRO SER SER GLU GLN LEU THR SER GLY GLY ALA SER
SEQRES 11 D 213 VAL VAL CYS PHE LEU ASN ASN PHE TYR PRO LYS ASP ILE
SEQRES 12 D 213 ASN VAL LYS TRP LYS ILE ASP GLY SER GLU ARG GLN ASN
SEQRES 13 D 213 GLY VAL LEU ASN SER TRP THR ASP GLN ASP SER LYS ASP
SEQRES 14 D 213 SER THR TYR SER MET SER SER THR LEU THR LEU THR LYS
SEQRES 15 D 213 ASP GLU TYR GLU ARG HIS ASN SER TYR THR CYS GLU ALA
SEQRES 16 D 213 THR HIS LYS THR SER THR SER PRO ILE VAL LYS SER PHE
SEQRES 17 D 213 ASN ARG ASN GLU CYS
SEQRES 1 E 224 GLN VAL GLN LEU GLN GLN SER GLY ALA GLU LEU MET LYS
SEQRES 2 E 224 PRO GLY ALA SER VAL LYS ILE SER CYS LYS ALA THR GLY
SEQRES 3 E 224 TYR THR PHE SER SER TYR TRP ILE GLU TRP VAL LYS GLN
SEQRES 4 E 224 ARG PRO GLY HIS GLY LEU GLU TRP ILE GLY GLU ILE LEU
SEQRES 5 E 224 PRO GLY SER GLY SER THR ASN TYR ASN GLU ARG PHE LYS
SEQRES 6 E 224 GLY LYS ALA SER PHE THR ALA ASP SER SER SER ASN THR
SEQRES 7 E 224 ALA TYR MET GLN LEU SER SER LEU THR SER GLU ASP SER
SEQRES 8 E 224 ALA VAL TYR TYR CYS THR ARG THR SER TYR TYR PHE GLY
SEQRES 9 E 224 SER SER TYR ASP PHE ASP VAL TRP GLY ALA GLY THR THR
SEQRES 10 E 224 VAL THR VAL SER SER ALA LYS THR THR ALA PRO SER VAL
SEQRES 11 E 224 TYR PRO LEU ALA PRO VAL CYS GLY ASP THR THR GLY SER
SEQRES 12 E 224 SER VAL THR LEU GLY CYS LEU VAL LYS GLY TYR PHE PRO
SEQRES 13 E 224 GLU PRO VAL THR LEU THR TRP ASN SER GLY SER LEU SER
SEQRES 14 E 224 SER GLY VAL HIS THR PHE PRO ALA LEU LEU GLN SER ASP
SEQRES 15 E 224 LEU TYR THR LEU SER SER SER VAL THR VAL THR SER SER
SEQRES 16 E 224 THR TRP PRO SER GLN SER ILE THR CYS ASN VAL ALA HIS
SEQRES 17 E 224 PRO ALA SER SER THR LYS VAL ASP LYS LYS ILE GLU PRO
SEQRES 18 E 224 ARG GLY PRO
SEQRES 1 F 214 ASP ILE GLN MET THR GLN SER PRO SER SER LEU SER ALA
SEQRES 2 F 214 SER LEU GLY GLU ARG VAL SER LEU THR CYS ARG ALA SER
SEQRES 3 F 214 GLN GLU ILE SER GLY TYR LEU SER TRP LEU GLN GLN LYS
SEQRES 4 F 214 PRO ASP GLY THR ILE LYS ARG LEU ILE TYR ALA ALA SER
SEQRES 5 F 214 THR LEU ASP SER SER VAL PRO LYS ARG PHE SER GLY SER
SEQRES 6 F 214 ARG SER GLY SER ASP TYR SER LEU THR ILE SER SER LEU
SEQRES 7 F 214 ASP SER GLU ASP PHE ALA VAL TYR TYR CYS LEU GLN TYR
SEQRES 8 F 214 ALA SER TYR PRO TYR THR PHE GLY GLY GLY THR LYS VAL
SEQRES 9 F 214 GLU ILE LYS ARG ALA ASP ALA ALA PRO THR VAL SER ILE
SEQRES 10 F 214 PHE PRO PRO SER SER GLU GLN LEU THR SER GLY GLY ALA
SEQRES 11 F 214 SER VAL VAL CYS PHE LEU ASN ASN PHE TYR PRO LYS ASP
SEQRES 12 F 214 ILE ASN VAL LYS TRP LYS ILE ASP GLY SER GLU ARG GLN
SEQRES 13 F 214 ASN GLY VAL LEU ASN SER TRP THR ASP GLN ASP SER LYS
SEQRES 14 F 214 ASP SER THR TYR SER MET SER SER THR LEU THR LEU THR
SEQRES 15 F 214 LYS ASP GLU TYR GLU ARG HIS ASN SER TYR THR CYS GLU
SEQRES 16 F 214 ALA THR HIS LYS THR SER THR SER PRO ILE VAL LYS SER
SEQRES 17 F 214 PHE ASN ARG ASN GLU CYS
SEQRES 1 M 183 MET GLY SER SER HIS HIS HIS HIS HIS HIS SER SER GLY
SEQRES 2 M 183 LEU VAL PRO ARG GLY SER HIS MET LEU ASN SER CYS SER
SEQRES 3 M 183 MET PRO LEU GLY MET GLU SER LYS ALA ILE SER ASP ALA
SEQRES 4 M 183 GLN ILE THR ALA SER SER TYR PHE THR ASN MET PHE ALA
SEQRES 5 M 183 THR TRP SER PRO SER LYS ALA ARG LEU HIS LEU GLN GLY
SEQRES 6 M 183 ARG SER ASN ALA TRP ARG PRO GLN VAL ASN ASN PRO LYS
SEQRES 7 M 183 GLU TRP LEU GLN VAL ASP PHE GLN LYS THR MET LYS VAL
SEQRES 8 M 183 THR GLY VAL THR THR GLN GLY VAL LYS SER LEU LEU THR
SEQRES 9 M 183 SER MET TYR VAL LYS GLU PHE LEU ILE SER SER SER GLN
SEQRES 10 M 183 ASP GLY HIS GLN TRP THR LEU PHE PHE GLN ASN GLY LYS
SEQRES 11 M 183 VAL LYS VAL PHE GLN GLY ASN GLN ASP SER PHE THR PRO
SEQRES 12 M 183 VAL VAL ASN SER LEU ASP PRO PRO LEU LEU THR ARG TYR
SEQRES 13 M 183 LEU ARG ILE HIS PRO GLN SER TRP VAL HIS GLN ILE ALA
SEQRES 14 M 183 LEU ARG MET GLU VAL LEU GLY CYS GLU ALA GLN ASP LEU
SEQRES 15 M 183 TYR
FORMUL 6 HOH *267(H2 O)
HELIX 1 1 ASP C 26 TYR C 32 5 7
HELIX 2 2 ASP C 62 LYS C 65 5 4
HELIX 3 3 THR C 74 VAL C 76 5 3
HELIX 4 4 LYS C 87 THR C 91 5 5
HELIX 5 5 PRO C 129 ASP C 133 5 5
HELIX 6 6 PRO C 203 SER C 206 5 4
HELIX 7 7 GLU D 78 ALA D 82 5 5
HELIX 8 8 SER D 120 GLY D 127 1 8
HELIX 9 9 LYS D 182 GLU D 186 1 5
HELIX 10 10 THR E 28 SER E 30 5 3
HELIX 11 11 GLU E 62 LYS E 65 5 4
HELIX 12 12 THR E 87 SER E 91 5 5
HELIX 13 13 PRO E 135 ASP E 139 5 5
HELIX 14 14 SER E 165 SER E 167 5 3
HELIX 15 15 PRO E 209 SER E 212 5 4
HELIX 16 16 ASP F 79 PHE F 83 5 5
HELIX 17 17 SER F 121 SER F 127 1 7
HELIX 18 18 LYS F 183 GLU F 187 1 5
HELIX 19 19 SER M 2186 ALA M 2188 5 3
HELIX 20 20 SER M 2204 ALA M 2208 5 5
SHEET 1 A 4 LEU C 4 GLN C 6 0
SHEET 2 A 4 VAL C 18 ALA C 24 -1 O LYS C 23 N VAL C 5
SHEET 3 A 4 THR C 78 ILE C 83 -1 O LEU C 81 N ILE C 20
SHEET 4 A 4 PHE C 68 GLU C 73 -1 N ALA C 69 O GLN C 82
SHEET 1 B 6 GLU C 10 LYS C 12 0
SHEET 2 B 6 THR C 110 VAL C 114 1 O THR C 111 N GLU C 10
SHEET 3 B 6 ALA C 92 GLU C 99 -1 N ALA C 92 O LEU C 112
SHEET 4 B 6 LEU C 34 GLN C 39 -1 N HIS C 35 O ALA C 97
SHEET 5 B 6 LYS C 46 ILE C 51 -1 O LYS C 46 N LYS C 38
SHEET 6 B 6 PRO C 58 TYR C 60 -1 O ALA C 59 N TRP C 50
SHEET 1 C 4 GLU C 10 LYS C 12 0
SHEET 2 C 4 THR C 110 VAL C 114 1 O THR C 111 N GLU C 10
SHEET 3 C 4 ALA C 92 GLU C 99 -1 N ALA C 92 O LEU C 112
SHEET 4 C 4 LEU C 103 TRP C 106 -1 O SER C 105 N ARG C 98
SHEET 1 D 4 SER C 123 LEU C 127 0
SHEET 2 D 4 SER C 138 TYR C 148 -1 O LYS C 146 N SER C 123
SHEET 3 D 4 TYR C 178 THR C 187 -1 O LEU C 180 N VAL C 145
SHEET 4 D 4 VAL C 166 LEU C 173 -1 N HIS C 167 O SER C 183
SHEET 1 E 3 THR C 154 TRP C 157 0
SHEET 2 E 3 THR C 197 HIS C 202 -1 O ASN C 199 N THR C 156
SHEET 3 E 3 THR C 207 LYS C 212 -1 O VAL C 209 N VAL C 200
SHEET 1 F 4 LEU D 4 SER D 7 0
SHEET 2 F 4 VAL D 19 ALA D 25 -1 O SER D 24 N THR D 5
SHEET 3 F 4 SER D 69 ILE D 74 -1 O LEU D 72 N MET D 21
SHEET 4 F 4 PHE D 61 SER D 66 -1 N SER D 62 O THR D 73
SHEET 1 G 6 ILE D 10 ALA D 13 0
SHEET 2 G 6 THR D 101 LEU D 105 1 O LYS D 102 N MET D 11
SHEET 3 G 6 ALA D 83 HIS D 89 -1 N ALA D 83 O LEU D 103
SHEET 4 G 6 TYR D 33 GLN D 37 -1 N TYR D 33 O GLN D 88
SHEET 5 G 6 ARG D 44 SER D 48 -1 O LEU D 46 N TRP D 34
SHEET 6 G 6 ASN D 52 LEU D 53 -1 O ASN D 52 N SER D 48
SHEET 1 H 4 ILE D 10 ALA D 13 0
SHEET 2 H 4 THR D 101 LEU D 105 1 O LYS D 102 N MET D 11
SHEET 3 H 4 ALA D 83 HIS D 89 -1 N ALA D 83 O LEU D 103
SHEET 4 H 4 THR D 96 PHE D 97 -1 O THR D 96 N HIS D 89
SHEET 1 I 4 THR D 113 PHE D 117 0
SHEET 2 I 4 GLY D 128 PHE D 138 -1 O ASN D 136 N THR D 113
SHEET 3 I 4 TYR D 172 THR D 181 -1 O LEU D 180 N ALA D 129
SHEET 4 I 4 VAL D 158 TRP D 162 -1 N LEU D 159 O THR D 177
SHEET 1 J 4 SER D 152 ARG D 154 0
SHEET 2 J 4 ASN D 144 ILE D 149 -1 N ILE D 149 O SER D 152
SHEET 3 J 4 SER D 190 THR D 196 -1 O THR D 196 N ASN D 144
SHEET 4 J 4 ILE D 204 ASN D 209 -1 O LYS D 206 N CYS D 193
SHEET 1 K 4 GLN E 3 GLN E 6 0
SHEET 2 K 4 VAL E 18 THR E 25 -1 O LYS E 23 N GLN E 5
SHEET 3 K 4 THR E 78 LEU E 83 -1 O ALA E 79 N CYS E 22
SHEET 4 K 4 ALA E 68 ASP E 73 -1 N ASP E 73 O THR E 78
SHEET 1 L 6 GLU E 10 MET E 12 0
SHEET 2 L 6 THR E 116 VAL E 120 1 O THR E 117 N GLU E 10
SHEET 3 L 6 ALA E 92 SER E 100 -1 N ALA E 92 O VAL E 118
SHEET 4 L 6 TYR E 32 GLN E 39 -1 N VAL E 37 O TYR E 95
SHEET 5 L 6 LEU E 45 ILE E 51 -1 O GLU E 46 N LYS E 38
SHEET 6 L 6 THR E 58 TYR E 60 -1 O ASN E 59 N GLU E 50
SHEET 1 M 4 SER E 129 LEU E 133 0
SHEET 2 M 4 SER E 144 TYR E 154 -1 O LEU E 150 N TYR E 131
SHEET 3 M 4 LEU E 183 THR E 193 -1 O LEU E 186 N VAL E 151
SHEET 4 M 4 VAL E 172 THR E 174 -1 N HIS E 173 O SER E 189
SHEET 1 N 4 SER E 129 LEU E 133 0
SHEET 2 N 4 SER E 144 TYR E 154 -1 O LEU E 150 N TYR E 131
SHEET 3 N 4 LEU E 183 THR E 193 -1 O LEU E 186 N VAL E 151
SHEET 4 N 4 LEU E 178 GLN E 180 -1 N GLN E 180 O LEU E 183
SHEET 1 O 3 THR E 160 TRP E 163 0
SHEET 2 O 3 THR E 203 HIS E 208 -1 O ASN E 205 N THR E 162
SHEET 3 O 3 THR E 213 LYS E 218 -1 O LYS E 217 N CYS E 204
SHEET 1 P 4 MET F 4 SER F 7 0
SHEET 2 P 4 VAL F 19 ALA F 25 -1 O THR F 22 N SER F 7
SHEET 3 P 4 ASP F 70 ILE F 75 -1 O TYR F 71 N CYS F 23
SHEET 4 P 4 PHE F 62 SER F 67 -1 N SER F 67 O ASP F 70
SHEET 1 Q 6 SER F 10 SER F 14 0
SHEET 2 Q 6 THR F 102 LYS F 107 1 O LYS F 107 N ALA F 13
SHEET 3 Q 6 ALA F 84 GLN F 90 -1 N ALA F 84 O VAL F 104
SHEET 4 Q 6 LEU F 33 GLN F 38 -1 N LEU F 36 O TYR F 87
SHEET 5 Q 6 ILE F 44 TYR F 49 -1 O LEU F 47 N TRP F 35
SHEET 6 Q 6 THR F 53 LEU F 54 -1 O THR F 53 N TYR F 49
SHEET 1 R 4 SER F 10 SER F 14 0
SHEET 2 R 4 THR F 102 LYS F 107 1 O LYS F 107 N ALA F 13
SHEET 3 R 4 ALA F 84 GLN F 90 -1 N ALA F 84 O VAL F 104
SHEET 4 R 4 THR F 97 PHE F 98 -1 O THR F 97 N GLN F 90
SHEET 1 S 4 THR F 114 PHE F 118 0
SHEET 2 S 4 GLY F 129 PHE F 139 -1 O PHE F 135 N SER F 116
SHEET 3 S 4 TYR F 173 THR F 182 -1 O LEU F 179 N VAL F 132
SHEET 4 S 4 VAL F 159 TRP F 163 -1 N SER F 162 O SER F 176
SHEET 1 T 4 SER F 153 ARG F 155 0
SHEET 2 T 4 ASN F 145 ILE F 150 -1 N ILE F 150 O SER F 153
SHEET 3 T 4 SER F 191 THR F 197 -1 O GLU F 195 N LYS F 147
SHEET 4 T 4 ILE F 205 ASN F 210 -1 O LYS F 207 N CYS F 194
SHEET 1 U 6 MET M2176 PRO M2177 0
SHEET 2 U 6 ARG M2320 CYS M2326 -1 O GLY M2325 N MET M2176
SHEET 3 U 6 LEU M2230 GLN M2246 -1 N LYS M2239 O CYS M2326
SHEET 4 U 6 VAL M2293 VAL M2314 -1 O LEU M2301 N VAL M2240
SHEET 5 U 6 THR M2253 SER M2265 -1 N TYR M2256 O VAL M2314
SHEET 6 U 6 PHE M2283 GLN M2284 -1 O PHE M2283 N PHE M2260
SHEET 1 V 5 VAL M2248 SER M2250 0
SHEET 2 V 5 THR M2253 SER M2265 -1 O MET M2255 N VAL M2248
SHEET 3 V 5 VAL M2293 VAL M2314 -1 O VAL M2314 N TYR M2256
SHEET 4 V 5 LEU M2230 GLN M2246 -1 N VAL M2240 O LEU M2301
SHEET 5 V 5 ILE M2190 ALA M2192 -1 N THR M2191 O GLN M2231
SHEET 1 W 6 THR M2272 LEU M2273 0
SHEET 2 W 6 THR M2253 SER M2265 -1 N SER M2264 O THR M2272
SHEET 3 W 6 VAL M2293 VAL M2314 -1 O VAL M2314 N TYR M2256
SHEET 4 W 6 LEU M2230 GLN M2246 -1 N VAL M2240 O LEU M2301
SHEET 5 W 6 ARG M2320 CYS M2326 -1 O CYS M2326 N LYS M2239
SHEET 6 W 6 MET M2176 PRO M2177 -1 N MET M2176 O GLY M2325
SHEET 1 X 2 PHE M2275 GLN M2276 0
SHEET 2 X 2 LYS M2279 VAL M2280 -1 O LYS M2279 N GLN M2276
SSBOND 1 CYS C 22 CYS C 96 1555 1555 2.03
SSBOND 2 CYS C 131 CYS D 213 1555 1555 2.16
SSBOND 3 CYS C 143 CYS C 198 1555 1555 2.04
SSBOND 4 CYS D 23 CYS D 87 1555 1555 2.04
SSBOND 5 CYS D 133 CYS D 193 1555 1555 2.03
SSBOND 6 CYS E 22 CYS E 96 1555 1555 2.03
SSBOND 7 CYS E 137 CYS F 214 1555 1555 2.03
SSBOND 8 CYS E 149 CYS E 204 1555 1555 2.03
SSBOND 9 CYS F 23 CYS F 88 1555 1555 2.03
SSBOND 10 CYS F 134 CYS F 194 1555 1555 2.03
SSBOND 11 CYS M 2174 CYS M 2326 1555 1555 2.03
CISPEP 1 PHE C 149 PRO C 150 0 -0.02
CISPEP 2 GLU C 151 PRO C 152 0 1.66
CISPEP 3 GLN C 174 SER C 175 0 2.65
CISPEP 4 TRP C 191 PRO C 192 0 4.32
CISPEP 5 SER D 7 PRO D 8 0 -3.16
CISPEP 6 TYR D 93 PRO D 94 0 -1.78
CISPEP 7 TYR D 139 PRO D 140 0 -1.52
CISPEP 8 PHE E 155 PRO E 156 0 1.08
CISPEP 9 GLU E 157 PRO E 158 0 0.85
CISPEP 10 TRP E 197 PRO E 198 0 3.79
CISPEP 11 SER F 7 PRO F 8 0 7.75
CISPEP 12 GLY F 68 SER F 69 0 0.70
CISPEP 13 TYR F 94 PRO F 95 0 -0.89
CISPEP 14 TYR F 140 PRO F 141 0 2.45
CISPEP 15 ASP M 2298 PRO M 2299 0 3.51
CRYST1 54.250 71.160 277.850 90.00 90.00 90.00 P 2 21 21 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 0.018433 0.000000 0.000000 0.00000
SCALE2 0.000000 0.014053 0.000000 0.00000
SCALE3 0.000000 0.000000 0.003599 0.00000
(ATOM LINES ARE NOT SHOWN.)
END
