HEADER HYDROLASE 20-OCT-09 3KC1
TITLE CRYSTAL STRUCTURE OF HUMAN LIVER FBPASE IN COMPLEX WITH TRICYCLIC
TITLE 2 INHIBITOR 19A
COMPND MOL_ID: 1;
COMPND 2 MOLECULE: FRUCTOSE-1,6-BISPHOSPHATASE 1;
COMPND 3 CHAIN: A, B, C, D;
COMPND 4 SYNONYM: FBPASE 1, D-FRUCTOSE-1,6-BISPHOSPHATE 1-PHOSPHOHYDROLASE 1;
COMPND 5 EC: 3.1.3.11;
COMPND 6 ENGINEERED: YES
SOURCE MOL_ID: 1;
SOURCE 2 ORGANISM_SCIENTIFIC: HOMO SAPIENS;
SOURCE 3 ORGANISM_COMMON: HUMAN;
SOURCE 4 ORGANISM_TAXID: 9606;
SOURCE 5 EXPRESSION_SYSTEM: ESCHERICHIA COLI;
SOURCE 6 EXPRESSION_SYSTEM_TAXID: 562;
SOURCE 7 EXPRESSION_SYSTEM_STRAIN: BL21(DE3);
SOURCE 8 EXPRESSION_SYSTEM_VECTOR_TYPE: PLASMID;
SOURCE 9 EXPRESSION_SYSTEM_PLASMID: PET3A
KEYWDS HYDROLASE, ALLOSTERIC ENZYME, CARBOHYDRATE METABOLISM, DISEASE
KEYWDS 2 MUTATION, GLUCONEOGENESIS, MAGNESIUM, METAL-BINDING, POLYMORPHISM
EXPDTA X-RAY DIFFRACTION
AUTHOR M.TAKAHASHI,J.SONE,H.HANZAWA
REVDAT 3 01-NOV-23 3KC1 1 REMARK
REVDAT 2 01-NOV-17 3KC1 1 REMARK
REVDAT 1 02-FEB-10 3KC1 0
JRNL AUTH T.TSUKADA,M.TAKAHASHI,T.TAKEMOTO,O.KANNO,T.YAMANE,
JRNL AUTH 2 S.KAWAMURA,T.NISHI
JRNL TITL STRUCTURE-BASED DRUG DESIGN OF TRICYCLIC
JRNL TITL 2 8H-INDENO[1,2-D][1,3]THIAZOLES AS POTENT FBPASE INHIBITORS.
JRNL REF BIOORG.MED.CHEM.LETT. V. 20 1004 2010
JRNL REFN ISSN 0960-894X
JRNL PMID 20045638
JRNL DOI 10.1016/J.BMCL.2009.12.056
REMARK 2
REMARK 2 RESOLUTION. 2.25 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) : 2.25
REMARK 3 RESOLUTION RANGE LOW (ANGSTROMS) : 19.88
REMARK 3 DATA CUTOFF (SIGMA(F)) : 0.000
REMARK 3 DATA CUTOFF HIGH (ABS(F)) : 1193535.000
REMARK 3 DATA CUTOFF LOW (ABS(F)) : 0.0000
REMARK 3 COMPLETENESS (WORKING+TEST) (%) : 95.9
REMARK 3 NUMBER OF REFLECTIONS : 71871
REMARK 3
REMARK 3 FIT TO DATA USED IN REFINEMENT.
REMARK 3 CROSS-VALIDATION METHOD : THROUGHOUT
REMARK 3 FREE R VALUE TEST SET SELECTION : NULL
REMARK 3 R VALUE (WORKING + TEST SET) : 0.228
REMARK 3 R VALUE (WORKING SET) : 0.228
REMARK 3 FREE R VALUE : 0.262
REMARK 3 FREE R VALUE TEST SET SIZE (%) : 9.900
REMARK 3 FREE R VALUE TEST SET COUNT : 7151
REMARK 3 ESTIMATED ERROR OF FREE R VALUE : 0.003
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 : 6
REMARK 3 BIN RESOLUTION RANGE HIGH (A) : 2.25
REMARK 3 BIN RESOLUTION RANGE LOW (A) : 2.39
REMARK 3 BIN COMPLETENESS (WORKING+TEST) (%) : 96.60
REMARK 3 REFLECTIONS IN BIN (WORKING SET) : 10758
REMARK 3 BIN R VALUE (WORKING SET) : 0.2130
REMARK 3 BIN FREE R VALUE : 0.2610
REMARK 3 BIN FREE R VALUE TEST SET SIZE (%) : 9.70
REMARK 3 BIN FREE R VALUE TEST SET COUNT : 1155
REMARK 3 ESTIMATED ERROR OF BIN FREE R VALUE : 0.008
REMARK 3
REMARK 3 NUMBER OF NON-HYDROGEN ATOMS USED IN REFINEMENT.
REMARK 3 PROTEIN ATOMS : 9734
REMARK 3 NUCLEIC ACID ATOMS : 0
REMARK 3 HETEROGEN ATOMS : 84
REMARK 3 SOLVENT ATOMS : 355
REMARK 3
REMARK 3 B VALUES.
REMARK 3 FROM WILSON PLOT (A**2) : NULL
REMARK 3 MEAN B VALUE (OVERALL, A**2) : 25.56
REMARK 3 OVERALL ANISOTROPIC B VALUE.
REMARK 3 B11 (A**2) : 3.36000
REMARK 3 B22 (A**2) : -2.36000
REMARK 3 B33 (A**2) : -1.00000
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) : 0.27
REMARK 3 ESD FROM SIGMAA (A) : 0.04
REMARK 3 LOW RESOLUTION CUTOFF (A) : 5.00
REMARK 3
REMARK 3 CROSS-VALIDATED ESTIMATED COORDINATE ERROR.
REMARK 3 ESD FROM C-V LUZZATI PLOT (A) : 0.32
REMARK 3 ESD FROM C-V SIGMAA (A) : 0.16
REMARK 3
REMARK 3 RMS DEVIATIONS FROM IDEAL VALUES.
REMARK 3 BOND LENGTHS (A) : 0.007
REMARK 3 BOND ANGLES (DEGREES) : 1.400
REMARK 3 DIHEDRAL ANGLES (DEGREES) : 23.10
REMARK 3 IMPROPER ANGLES (DEGREES) : 0.780
REMARK 3
REMARK 3 ISOTROPIC THERMAL MODEL : RESTRAINED
REMARK 3
REMARK 3 ISOTROPIC THERMAL FACTOR RESTRAINTS. RMS SIGMA
REMARK 3 MAIN-CHAIN BOND (A**2) : 1.020 ; 1.500
REMARK 3 MAIN-CHAIN ANGLE (A**2) : 1.600 ; 2.000
REMARK 3 SIDE-CHAIN BOND (A**2) : 1.690 ; 2.000
REMARK 3 SIDE-CHAIN ANGLE (A**2) : 2.380 ; 2.500
REMARK 3
REMARK 3 BULK SOLVENT MODELING.
REMARK 3 METHOD USED : FLAT MODEL
REMARK 3 KSOL : 0.40
REMARK 3 BSOL : 39.91
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 : PROTEIN_REP.PARAM
REMARK 3 PARAMETER FILE 2 : WATER.PARAM
REMARK 3 PARAMETER FILE 3 : COMPD19A.PARAM
REMARK 3 PARAMETER FILE 4 : NULL
REMARK 3 TOPOLOGY FILE 1 : PROTEIN.TOP
REMARK 3 TOPOLOGY FILE 2 : WATER.TOP
REMARK 3 TOPOLOGY FILE 3 : COMPD19A.TOP
REMARK 3 TOPOLOGY FILE 4 : NULL
REMARK 3
REMARK 3 OTHER REFINEMENT REMARKS: BULK SOLVENT MODEL USED
REMARK 4
REMARK 4 3KC1 COMPLIES WITH FORMAT V. 3.30, 13-JUL-11
REMARK 100
REMARK 100 THIS ENTRY HAS BEEN PROCESSED BY PDBJ ON 22-OCT-09.
REMARK 100 THE DEPOSITION ID IS D_1000055802.
REMARK 200
REMARK 200 EXPERIMENTAL DETAILS
REMARK 200 EXPERIMENT TYPE : X-RAY DIFFRACTION
REMARK 200 DATE OF DATA COLLECTION : 10-JUN-05
REMARK 200 TEMPERATURE (KELVIN) : 93
REMARK 200 PH : 8.5
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 FR-E SUPERBRIGHT
REMARK 200 MONOCHROMATIC OR LAUE (M/L) : M
REMARK 200 WAVELENGTH OR RANGE (A) : 1.542
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 : DENZO, HKL-2000
REMARK 200 DATA SCALING SOFTWARE : SCALEPACK, HKL-2000
REMARK 200
REMARK 200 NUMBER OF UNIQUE REFLECTIONS : 71995
REMARK 200 RESOLUTION RANGE HIGH (A) : 2.250
REMARK 200 RESOLUTION RANGE LOW (A) : 40.000
REMARK 200 REJECTION CRITERIA (SIGMA(I)) : NULL
REMARK 200
REMARK 200 OVERALL.
REMARK 200 COMPLETENESS FOR RANGE (%) : 95.2
REMARK 200 DATA REDUNDANCY : 4.600
REMARK 200 R MERGE (I) : 0.06100
REMARK 200 R SYM (I) : NULL
REMARK 200 <I/SIGMA(I)> FOR THE DATA SET : 23.9000
REMARK 200
REMARK 200 IN THE HIGHEST RESOLUTION SHELL.
REMARK 200 HIGHEST RESOLUTION SHELL, RANGE HIGH (A) : 2.25
REMARK 200 HIGHEST RESOLUTION SHELL, RANGE LOW (A) : 2.33
REMARK 200 COMPLETENESS FOR SHELL (%) : 90.7
REMARK 200 DATA REDUNDANCY IN SHELL : 4.60
REMARK 200 R MERGE FOR SHELL (I) : 0.10100
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 2000.1
REMARK 200 STARTING MODEL: 1FTA
REMARK 200
REMARK 200 REMARK: NULL
REMARK 280
REMARK 280 CRYSTAL
REMARK 280 SOLVENT CONTENT, VS (%): 53.64
REMARK 280 MATTHEWS COEFFICIENT, VM (ANGSTROMS**3/DA): 2.65
REMARK 280
REMARK 280 CRYSTALLIZATION CONDITIONS: 8-10% PEG 3350, 0.15M NACL, 0.1M
REMARK 280 TRIS/HCL, PH 8.5, VAPOR DIFFUSION, HANGING DROP, TEMPERATURE 295K
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 33.67900
REMARK 290 SMTRY2 2 0.000000 -1.000000 0.000000 0.00000
REMARK 290 SMTRY3 2 0.000000 0.000000 1.000000 139.07350
REMARK 290 SMTRY1 3 -1.000000 0.000000 0.000000 0.00000
REMARK 290 SMTRY2 3 0.000000 1.000000 0.000000 41.60650
REMARK 290 SMTRY3 3 0.000000 0.000000 -1.000000 139.07350
REMARK 290 SMTRY1 4 1.000000 0.000000 0.000000 33.67900
REMARK 290 SMTRY2 4 0.000000 -1.000000 0.000000 41.60650
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: TETRAMERIC
REMARK 350 SOFTWARE DETERMINED QUATERNARY STRUCTURE: TETRAMERIC
REMARK 350 SOFTWARE USED: PISA
REMARK 350 TOTAL BURIED SURFACE AREA: 15200 ANGSTROM**2
REMARK 350 SURFACE AREA OF THE COMPLEX: 44230 ANGSTROM**2
REMARK 350 CHANGE IN SOLVENT FREE ENERGY: -87.0 KCAL/MOL
REMARK 350 APPLY THE FOLLOWING TO CHAINS: A, B, C, D
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 ALA A 1
REMARK 465 ASP A 2
REMARK 465 GLN A 3
REMARK 465 ALA A 4
REMARK 465 PRO A 5
REMARK 465 PHE A 6
REMARK 465 ASP A 7
REMARK 465 THR A 8
REMARK 465 SER A 62
REMARK 465 THR A 63
REMARK 465 ASN A 64
REMARK 465 VAL A 65
REMARK 465 THR A 66
REMARK 465 GLY A 67
REMARK 465 ASP A 68
REMARK 465 GLN A 69
REMARK 465 ALA A 336
REMARK 465 GLN A 337
REMARK 465 ALA B 1
REMARK 465 ASP B 2
REMARK 465 GLN B 3
REMARK 465 ALA B 4
REMARK 465 PRO B 5
REMARK 465 PHE B 6
REMARK 465 ASP B 7
REMARK 465 THR B 8
REMARK 465 SER B 62
REMARK 465 THR B 63
REMARK 465 ASN B 64
REMARK 465 VAL B 65
REMARK 465 THR B 66
REMARK 465 GLY B 67
REMARK 465 ASP B 68
REMARK 465 GLN B 69
REMARK 465 VAL B 70
REMARK 465 ALA B 336
REMARK 465 GLN B 337
REMARK 465 ALA C 1
REMARK 465 ASP C 2
REMARK 465 GLN C 3
REMARK 465 ALA C 4
REMARK 465 PRO C 5
REMARK 465 PHE C 6
REMARK 465 ASP C 7
REMARK 465 THR C 8
REMARK 465 SER C 62
REMARK 465 THR C 63
REMARK 465 ASN C 64
REMARK 465 VAL C 65
REMARK 465 THR C 66
REMARK 465 GLY C 67
REMARK 465 ASP C 68
REMARK 465 GLN C 69
REMARK 465 VAL C 70
REMARK 465 ALA C 336
REMARK 465 GLN C 337
REMARK 465 ALA D 1
REMARK 465 ASP D 2
REMARK 465 GLN D 3
REMARK 465 ALA D 4
REMARK 465 PRO D 5
REMARK 465 PHE D 6
REMARK 465 ASP D 7
REMARK 465 THR D 8
REMARK 465 SER D 62
REMARK 465 THR D 63
REMARK 465 ASN D 64
REMARK 465 VAL D 65
REMARK 465 THR D 66
REMARK 465 GLY D 67
REMARK 465 ASP D 68
REMARK 465 GLN D 69
REMARK 465 VAL D 70
REMARK 465 LYS D 71
REMARK 465 ALA D 336
REMARK 465 GLN D 337
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 ASN A 125 50.81 -115.84
REMARK 500 LEU A 153 58.07 -91.53
REMARK 500 TYR A 167 77.77 -101.76
REMARK 500 ASP A 199 61.53 37.38
REMARK 500 ASN A 236 26.70 45.97
REMARK 500 ASN A 267 -170.91 -175.24
REMARK 500 GLU A 280 -59.34 -128.75
REMARK 500 TYR B 167 77.88 -101.28
REMARK 500 ASP B 199 60.60 38.82
REMARK 500 ASN B 267 -147.40 -128.05
REMARK 500 GLU B 280 -58.40 -129.93
REMARK 500 LEU C 153 57.74 -93.88
REMARK 500 TYR C 167 77.31 -100.99
REMARK 500 ASP C 199 60.83 38.16
REMARK 500 GLU C 280 -59.15 -128.07
REMARK 500 LEU D 153 56.61 -91.71
REMARK 500 TYR D 167 77.16 -101.54
REMARK 500 ASP D 199 61.94 37.28
REMARK 500 GLU D 280 -59.06 -129.10
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 2T6 A 401
REMARK 800
REMARK 800 SITE_IDENTIFIER: AC2
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: BINDING SITE FOR RESIDUE 2T6 B 401
REMARK 800
REMARK 800 SITE_IDENTIFIER: AC3
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: BINDING SITE FOR RESIDUE 2T6 C 401
REMARK 800
REMARK 800 SITE_IDENTIFIER: AC4
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: BINDING SITE FOR RESIDUE 2T6 D 401
REMARK 900
REMARK 900 RELATED ENTRIES
REMARK 900 RELATED ID: 3KBZ RELATED DB: PDB
REMARK 900 RELATED ID: 3KC0 RELATED DB: PDB
DBREF 3KC1 A 1 337 UNP P09467 F16P1_HUMAN 2 338
DBREF 3KC1 B 1 337 UNP P09467 F16P1_HUMAN 2 338
DBREF 3KC1 C 1 337 UNP P09467 F16P1_HUMAN 2 338
DBREF 3KC1 D 1 337 UNP P09467 F16P1_HUMAN 2 338
SEQRES 1 A 337 ALA ASP GLN ALA PRO PHE ASP THR ASP VAL ASN THR LEU
SEQRES 2 A 337 THR ARG PHE VAL MET GLU GLU GLY ARG LYS ALA ARG GLY
SEQRES 3 A 337 THR GLY GLU LEU THR GLN LEU LEU ASN SER LEU CYS THR
SEQRES 4 A 337 ALA VAL LYS ALA ILE SER SER ALA VAL ARG LYS ALA GLY
SEQRES 5 A 337 ILE ALA HIS LEU TYR GLY ILE ALA GLY SER THR ASN VAL
SEQRES 6 A 337 THR GLY ASP GLN VAL LYS LYS LEU ASP VAL LEU SER ASN
SEQRES 7 A 337 ASP LEU VAL MET ASN MET LEU LYS SER SER PHE ALA THR
SEQRES 8 A 337 CYS VAL LEU VAL SER GLU GLU ASP LYS HIS ALA ILE ILE
SEQRES 9 A 337 VAL GLU PRO GLU LYS ARG GLY LYS TYR VAL VAL CYS PHE
SEQRES 10 A 337 ASP PRO LEU ASP GLY SER SER ASN ILE ASP CYS LEU VAL
SEQRES 11 A 337 SER VAL GLY THR ILE PHE GLY ILE TYR ARG LYS LYS SER
SEQRES 12 A 337 THR ASP GLU PRO SER GLU LYS ASP ALA LEU GLN PRO GLY
SEQRES 13 A 337 ARG ASN LEU VAL ALA ALA GLY TYR ALA LEU TYR GLY SER
SEQRES 14 A 337 ALA THR MET LEU VAL LEU ALA MET ASP CYS GLY VAL ASN
SEQRES 15 A 337 CYS PHE MET LEU ASP PRO ALA ILE GLY GLU PHE ILE LEU
SEQRES 16 A 337 VAL ASP LYS ASP VAL LYS ILE LYS LYS LYS GLY LYS ILE
SEQRES 17 A 337 TYR SER LEU ASN GLU GLY TYR ALA LYS ASP PHE ASP PRO
SEQRES 18 A 337 ALA VAL THR GLU TYR ILE GLN ARG LYS LYS PHE PRO PRO
SEQRES 19 A 337 ASP ASN SER ALA PRO TYR GLY ALA ARG TYR VAL GLY SER
SEQRES 20 A 337 MET VAL ALA ASP VAL HIS ARG THR LEU VAL TYR GLY GLY
SEQRES 21 A 337 ILE PHE LEU TYR PRO ALA ASN LYS LYS SER PRO ASN GLY
SEQRES 22 A 337 LYS LEU ARG LEU LEU TYR GLU CYS ASN PRO MET ALA TYR
SEQRES 23 A 337 VAL MET GLU LYS ALA GLY GLY MET ALA THR THR GLY LYS
SEQRES 24 A 337 GLU ALA VAL LEU ASP VAL ILE PRO THR ASP ILE HIS GLN
SEQRES 25 A 337 ARG ALA PRO VAL ILE LEU GLY SER PRO ASP ASP VAL LEU
SEQRES 26 A 337 GLU PHE LEU LYS VAL TYR GLU LYS HIS SER ALA GLN
SEQRES 1 B 337 ALA ASP GLN ALA PRO PHE ASP THR ASP VAL ASN THR LEU
SEQRES 2 B 337 THR ARG PHE VAL MET GLU GLU GLY ARG LYS ALA ARG GLY
SEQRES 3 B 337 THR GLY GLU LEU THR GLN LEU LEU ASN SER LEU CYS THR
SEQRES 4 B 337 ALA VAL LYS ALA ILE SER SER ALA VAL ARG LYS ALA GLY
SEQRES 5 B 337 ILE ALA HIS LEU TYR GLY ILE ALA GLY SER THR ASN VAL
SEQRES 6 B 337 THR GLY ASP GLN VAL LYS LYS LEU ASP VAL LEU SER ASN
SEQRES 7 B 337 ASP LEU VAL MET ASN MET LEU LYS SER SER PHE ALA THR
SEQRES 8 B 337 CYS VAL LEU VAL SER GLU GLU ASP LYS HIS ALA ILE ILE
SEQRES 9 B 337 VAL GLU PRO GLU LYS ARG GLY LYS TYR VAL VAL CYS PHE
SEQRES 10 B 337 ASP PRO LEU ASP GLY SER SER ASN ILE ASP CYS LEU VAL
SEQRES 11 B 337 SER VAL GLY THR ILE PHE GLY ILE TYR ARG LYS LYS SER
SEQRES 12 B 337 THR ASP GLU PRO SER GLU LYS ASP ALA LEU GLN PRO GLY
SEQRES 13 B 337 ARG ASN LEU VAL ALA ALA GLY TYR ALA LEU TYR GLY SER
SEQRES 14 B 337 ALA THR MET LEU VAL LEU ALA MET ASP CYS GLY VAL ASN
SEQRES 15 B 337 CYS PHE MET LEU ASP PRO ALA ILE GLY GLU PHE ILE LEU
SEQRES 16 B 337 VAL ASP LYS ASP VAL LYS ILE LYS LYS LYS GLY LYS ILE
SEQRES 17 B 337 TYR SER LEU ASN GLU GLY TYR ALA LYS ASP PHE ASP PRO
SEQRES 18 B 337 ALA VAL THR GLU TYR ILE GLN ARG LYS LYS PHE PRO PRO
SEQRES 19 B 337 ASP ASN SER ALA PRO TYR GLY ALA ARG TYR VAL GLY SER
SEQRES 20 B 337 MET VAL ALA ASP VAL HIS ARG THR LEU VAL TYR GLY GLY
SEQRES 21 B 337 ILE PHE LEU TYR PRO ALA ASN LYS LYS SER PRO ASN GLY
SEQRES 22 B 337 LYS LEU ARG LEU LEU TYR GLU CYS ASN PRO MET ALA TYR
SEQRES 23 B 337 VAL MET GLU LYS ALA GLY GLY MET ALA THR THR GLY LYS
SEQRES 24 B 337 GLU ALA VAL LEU ASP VAL ILE PRO THR ASP ILE HIS GLN
SEQRES 25 B 337 ARG ALA PRO VAL ILE LEU GLY SER PRO ASP ASP VAL LEU
SEQRES 26 B 337 GLU PHE LEU LYS VAL TYR GLU LYS HIS SER ALA GLN
SEQRES 1 C 337 ALA ASP GLN ALA PRO PHE ASP THR ASP VAL ASN THR LEU
SEQRES 2 C 337 THR ARG PHE VAL MET GLU GLU GLY ARG LYS ALA ARG GLY
SEQRES 3 C 337 THR GLY GLU LEU THR GLN LEU LEU ASN SER LEU CYS THR
SEQRES 4 C 337 ALA VAL LYS ALA ILE SER SER ALA VAL ARG LYS ALA GLY
SEQRES 5 C 337 ILE ALA HIS LEU TYR GLY ILE ALA GLY SER THR ASN VAL
SEQRES 6 C 337 THR GLY ASP GLN VAL LYS LYS LEU ASP VAL LEU SER ASN
SEQRES 7 C 337 ASP LEU VAL MET ASN MET LEU LYS SER SER PHE ALA THR
SEQRES 8 C 337 CYS VAL LEU VAL SER GLU GLU ASP LYS HIS ALA ILE ILE
SEQRES 9 C 337 VAL GLU PRO GLU LYS ARG GLY LYS TYR VAL VAL CYS PHE
SEQRES 10 C 337 ASP PRO LEU ASP GLY SER SER ASN ILE ASP CYS LEU VAL
SEQRES 11 C 337 SER VAL GLY THR ILE PHE GLY ILE TYR ARG LYS LYS SER
SEQRES 12 C 337 THR ASP GLU PRO SER GLU LYS ASP ALA LEU GLN PRO GLY
SEQRES 13 C 337 ARG ASN LEU VAL ALA ALA GLY TYR ALA LEU TYR GLY SER
SEQRES 14 C 337 ALA THR MET LEU VAL LEU ALA MET ASP CYS GLY VAL ASN
SEQRES 15 C 337 CYS PHE MET LEU ASP PRO ALA ILE GLY GLU PHE ILE LEU
SEQRES 16 C 337 VAL ASP LYS ASP VAL LYS ILE LYS LYS LYS GLY LYS ILE
SEQRES 17 C 337 TYR SER LEU ASN GLU GLY TYR ALA LYS ASP PHE ASP PRO
SEQRES 18 C 337 ALA VAL THR GLU TYR ILE GLN ARG LYS LYS PHE PRO PRO
SEQRES 19 C 337 ASP ASN SER ALA PRO TYR GLY ALA ARG TYR VAL GLY SER
SEQRES 20 C 337 MET VAL ALA ASP VAL HIS ARG THR LEU VAL TYR GLY GLY
SEQRES 21 C 337 ILE PHE LEU TYR PRO ALA ASN LYS LYS SER PRO ASN GLY
SEQRES 22 C 337 LYS LEU ARG LEU LEU TYR GLU CYS ASN PRO MET ALA TYR
SEQRES 23 C 337 VAL MET GLU LYS ALA GLY GLY MET ALA THR THR GLY LYS
SEQRES 24 C 337 GLU ALA VAL LEU ASP VAL ILE PRO THR ASP ILE HIS GLN
SEQRES 25 C 337 ARG ALA PRO VAL ILE LEU GLY SER PRO ASP ASP VAL LEU
SEQRES 26 C 337 GLU PHE LEU LYS VAL TYR GLU LYS HIS SER ALA GLN
SEQRES 1 D 337 ALA ASP GLN ALA PRO PHE ASP THR ASP VAL ASN THR LEU
SEQRES 2 D 337 THR ARG PHE VAL MET GLU GLU GLY ARG LYS ALA ARG GLY
SEQRES 3 D 337 THR GLY GLU LEU THR GLN LEU LEU ASN SER LEU CYS THR
SEQRES 4 D 337 ALA VAL LYS ALA ILE SER SER ALA VAL ARG LYS ALA GLY
SEQRES 5 D 337 ILE ALA HIS LEU TYR GLY ILE ALA GLY SER THR ASN VAL
SEQRES 6 D 337 THR GLY ASP GLN VAL LYS LYS LEU ASP VAL LEU SER ASN
SEQRES 7 D 337 ASP LEU VAL MET ASN MET LEU LYS SER SER PHE ALA THR
SEQRES 8 D 337 CYS VAL LEU VAL SER GLU GLU ASP LYS HIS ALA ILE ILE
SEQRES 9 D 337 VAL GLU PRO GLU LYS ARG GLY LYS TYR VAL VAL CYS PHE
SEQRES 10 D 337 ASP PRO LEU ASP GLY SER SER ASN ILE ASP CYS LEU VAL
SEQRES 11 D 337 SER VAL GLY THR ILE PHE GLY ILE TYR ARG LYS LYS SER
SEQRES 12 D 337 THR ASP GLU PRO SER GLU LYS ASP ALA LEU GLN PRO GLY
SEQRES 13 D 337 ARG ASN LEU VAL ALA ALA GLY TYR ALA LEU TYR GLY SER
SEQRES 14 D 337 ALA THR MET LEU VAL LEU ALA MET ASP CYS GLY VAL ASN
SEQRES 15 D 337 CYS PHE MET LEU ASP PRO ALA ILE GLY GLU PHE ILE LEU
SEQRES 16 D 337 VAL ASP LYS ASP VAL LYS ILE LYS LYS LYS GLY LYS ILE
SEQRES 17 D 337 TYR SER LEU ASN GLU GLY TYR ALA LYS ASP PHE ASP PRO
SEQRES 18 D 337 ALA VAL THR GLU TYR ILE GLN ARG LYS LYS PHE PRO PRO
SEQRES 19 D 337 ASP ASN SER ALA PRO TYR GLY ALA ARG TYR VAL GLY SER
SEQRES 20 D 337 MET VAL ALA ASP VAL HIS ARG THR LEU VAL TYR GLY GLY
SEQRES 21 D 337 ILE PHE LEU TYR PRO ALA ASN LYS LYS SER PRO ASN GLY
SEQRES 22 D 337 LYS LEU ARG LEU LEU TYR GLU CYS ASN PRO MET ALA TYR
SEQRES 23 D 337 VAL MET GLU LYS ALA GLY GLY MET ALA THR THR GLY LYS
SEQRES 24 D 337 GLU ALA VAL LEU ASP VAL ILE PRO THR ASP ILE HIS GLN
SEQRES 25 D 337 ARG ALA PRO VAL ILE LEU GLY SER PRO ASP ASP VAL LEU
SEQRES 26 D 337 GLU PHE LEU LYS VAL TYR GLU LYS HIS SER ALA GLN
HET 2T6 A 401 21
HET 2T6 B 401 21
HET 2T6 C 401 21
HET 2T6 D 401 21
HETNAM 2T6 {[(7-CARBAMOYL-8H-INDENO[1,2-D][1,3]THIAZOL-4-YL)
HETNAM 2 2T6 OXY]METHYL}PHOSPHONIC ACID
FORMUL 5 2T6 4(C12 H11 N2 O5 P S)
FORMUL 9 HOH *355(H2 O)
HELIX 1 1 THR A 12 ARG A 25 1 14
HELIX 2 2 GLY A 28 ARG A 49 1 22
HELIX 3 3 GLY A 52 TYR A 57 1 6
HELIX 4 4 LYS A 72 SER A 87 1 16
HELIX 5 5 GLU A 106 GLU A 108 5 3
HELIX 6 6 GLY A 122 LEU A 129 5 8
HELIX 7 7 SER A 148 LEU A 153 5 6
HELIX 8 8 PRO A 155 LEU A 159 5 5
HELIX 9 9 ASN A 212 PHE A 219 5 8
HELIX 10 10 ASP A 220 PHE A 232 1 13
HELIX 11 11 SER A 247 GLY A 259 1 13
HELIX 12 12 GLU A 280 ALA A 291 1 12
HELIX 13 13 ALA A 301 VAL A 305 5 5
HELIX 14 14 SER A 320 HIS A 334 1 15
HELIX 15 15 THR B 12 ARG B 25 1 14
HELIX 16 16 GLY B 28 ARG B 49 1 22
HELIX 17 17 GLY B 52 TYR B 57 1 6
HELIX 18 18 LYS B 72 SER B 87 1 16
HELIX 19 19 GLU B 106 GLU B 108 5 3
HELIX 20 20 GLY B 122 LEU B 129 5 8
HELIX 21 21 SER B 148 LEU B 153 5 6
HELIX 22 22 PRO B 155 LEU B 159 5 5
HELIX 23 23 ASN B 212 PHE B 219 5 8
HELIX 24 24 ASP B 220 PHE B 232 1 13
HELIX 25 25 SER B 247 GLY B 259 1 13
HELIX 26 26 GLU B 280 ALA B 291 1 12
HELIX 27 27 ALA B 301 VAL B 305 5 5
HELIX 28 28 SER B 320 HIS B 334 1 15
HELIX 29 29 THR C 12 ARG C 25 1 14
HELIX 30 30 GLY C 28 ARG C 49 1 22
HELIX 31 31 GLY C 52 TYR C 57 1 6
HELIX 32 32 LYS C 72 SER C 87 1 16
HELIX 33 33 GLU C 106 GLU C 108 5 3
HELIX 34 34 GLY C 122 LEU C 129 5 8
HELIX 35 35 SER C 148 LEU C 153 5 6
HELIX 36 36 PRO C 155 LEU C 159 5 5
HELIX 37 37 ASN C 212 PHE C 219 5 8
HELIX 38 38 ASP C 220 PHE C 232 1 13
HELIX 39 39 SER C 247 GLY C 259 1 13
HELIX 40 40 GLU C 280 ALA C 291 1 12
HELIX 41 41 ALA C 301 VAL C 305 5 5
HELIX 42 42 SER C 320 HIS C 334 1 15
HELIX 43 43 THR D 12 ARG D 25 1 14
HELIX 44 44 GLY D 28 ARG D 49 1 22
HELIX 45 45 GLY D 52 TYR D 57 1 6
HELIX 46 46 LYS D 72 SER D 87 1 16
HELIX 47 47 GLU D 106 GLU D 108 5 3
HELIX 48 48 GLY D 122 LEU D 129 5 8
HELIX 49 49 SER D 148 LEU D 153 5 6
HELIX 50 50 PRO D 155 LEU D 159 5 5
HELIX 51 51 ASN D 212 PHE D 219 5 8
HELIX 52 52 ASP D 220 PHE D 232 1 13
HELIX 53 53 SER D 247 GLY D 259 1 13
HELIX 54 54 GLU D 280 ALA D 291 1 12
HELIX 55 55 ALA D 301 VAL D 305 5 5
HELIX 56 56 SER D 320 HIS D 334 1 15
SHEET 1 A 8 ILE A 103 ILE A 104 0
SHEET 2 A 8 THR A 91 SER A 96 -1 N LEU A 94 O ILE A 103
SHEET 3 A 8 ARG A 110 ASP A 121 1 O PHE A 117 N VAL A 95
SHEET 4 A 8 VAL A 132 ARG A 140 -1 O TYR A 139 N VAL A 114
SHEET 5 A 8 ALA A 161 TYR A 167 -1 O ALA A 161 N ILE A 138
SHEET 6 A 8 THR A 171 MET A 177 -1 O ALA A 176 N ALA A 162
SHEET 7 A 8 GLY A 180 LEU A 186 -1 O LEU A 186 N THR A 171
SHEET 8 A 8 PHE A 193 ASP A 197 -1 O ILE A 194 N MET A 185
SHEET 1 B 5 GLY A 241 ALA A 242 0
SHEET 2 B 5 ILE A 208 SER A 210 1 N TYR A 209 O GLY A 241
SHEET 3 B 5 ILE A 261 TYR A 264 1 O LEU A 263 N SER A 210
SHEET 4 B 5 VAL A 316 GLY A 319 -1 O LEU A 318 N PHE A 262
SHEET 5 B 5 MET A 294 THR A 296 -1 N THR A 296 O ILE A 317
SHEET 1 C 8 ILE B 103 ILE B 104 0
SHEET 2 C 8 THR B 91 SER B 96 -1 N LEU B 94 O ILE B 103
SHEET 3 C 8 ARG B 110 ASP B 121 1 O PHE B 117 N VAL B 95
SHEET 4 C 8 VAL B 132 ARG B 140 -1 O TYR B 139 N VAL B 114
SHEET 5 C 8 ALA B 161 TYR B 167 -1 O ALA B 161 N ILE B 138
SHEET 6 C 8 THR B 171 MET B 177 -1 O ALA B 176 N ALA B 162
SHEET 7 C 8 GLY B 180 LEU B 186 -1 O LEU B 186 N THR B 171
SHEET 8 C 8 PHE B 193 ASP B 197 -1 O ILE B 194 N MET B 185
SHEET 1 D 5 GLY B 241 ALA B 242 0
SHEET 2 D 5 ILE B 208 SER B 210 1 N TYR B 209 O GLY B 241
SHEET 3 D 5 ILE B 261 TYR B 264 1 O LEU B 263 N SER B 210
SHEET 4 D 5 VAL B 316 GLY B 319 -1 O LEU B 318 N PHE B 262
SHEET 5 D 5 MET B 294 THR B 296 -1 N THR B 296 O ILE B 317
SHEET 1 E 8 ILE C 103 ILE C 104 0
SHEET 2 E 8 THR C 91 SER C 96 -1 N LEU C 94 O ILE C 103
SHEET 3 E 8 ARG C 110 ASP C 121 1 O VAL C 115 N VAL C 95
SHEET 4 E 8 VAL C 132 ARG C 140 -1 O GLY C 133 N ASP C 121
SHEET 5 E 8 ALA C 161 TYR C 167 -1 O ALA C 161 N ILE C 138
SHEET 6 E 8 THR C 171 MET C 177 -1 O VAL C 174 N TYR C 164
SHEET 7 E 8 GLY C 180 LEU C 186 -1 O LEU C 186 N THR C 171
SHEET 8 E 8 PHE C 193 ASP C 197 -1 O ILE C 194 N MET C 185
SHEET 1 F 5 GLY C 241 ALA C 242 0
SHEET 2 F 5 ILE C 208 SER C 210 1 N TYR C 209 O GLY C 241
SHEET 3 F 5 ILE C 261 TYR C 264 1 O LEU C 263 N SER C 210
SHEET 4 F 5 VAL C 316 GLY C 319 -1 O LEU C 318 N PHE C 262
SHEET 5 F 5 MET C 294 THR C 296 -1 N THR C 296 O ILE C 317
SHEET 1 G 8 ILE D 103 ILE D 104 0
SHEET 2 G 8 THR D 91 SER D 96 -1 N LEU D 94 O ILE D 103
SHEET 3 G 8 ARG D 110 ASP D 121 1 O VAL D 115 N VAL D 95
SHEET 4 G 8 VAL D 132 ARG D 140 -1 O GLY D 133 N ASP D 121
SHEET 5 G 8 ALA D 161 TYR D 167 -1 O ALA D 161 N ILE D 138
SHEET 6 G 8 THR D 171 MET D 177 -1 O VAL D 174 N TYR D 164
SHEET 7 G 8 GLY D 180 LEU D 186 -1 O LEU D 186 N THR D 171
SHEET 8 G 8 PHE D 193 ASP D 197 -1 O ILE D 194 N MET D 185
SHEET 1 H 5 GLY D 241 ALA D 242 0
SHEET 2 H 5 ILE D 208 SER D 210 1 N TYR D 209 O GLY D 241
SHEET 3 H 5 ILE D 261 TYR D 264 1 O LEU D 263 N SER D 210
SHEET 4 H 5 VAL D 316 GLY D 319 -1 O LEU D 318 N PHE D 262
SHEET 5 H 5 MET D 294 THR D 296 -1 N THR D 296 O ILE D 317
SITE 1 AC1 17 VAL A 17 GLY A 21 ALA A 24 GLY A 26
SITE 2 AC1 17 THR A 27 GLY A 28 GLU A 29 LEU A 30
SITE 3 AC1 17 THR A 31 LYS A 112 TYR A 113 ARG A 140
SITE 4 AC1 17 ASP A 178 HOH A 345 HOH A 360 HOH A 361
SITE 5 AC1 17 HOH A 386
SITE 1 AC2 18 VAL B 17 GLU B 20 GLY B 21 ALA B 24
SITE 2 AC2 18 GLY B 26 THR B 27 GLY B 28 GLU B 29
SITE 3 AC2 18 LEU B 30 THR B 31 LYS B 112 TYR B 113
SITE 4 AC2 18 ARG B 140 MET B 177 HOH B 338 HOH B 353
SITE 5 AC2 18 HOH B 390 HOH B 392
SITE 1 AC3 18 VAL C 17 GLY C 21 ALA C 24 GLY C 26
SITE 2 AC3 18 THR C 27 GLY C 28 GLU C 29 LEU C 30
SITE 3 AC3 18 THR C 31 LYS C 112 TYR C 113 MET C 177
SITE 4 AC3 18 ASP C 178 HOH C 339 HOH C 350 HOH C 358
SITE 5 AC3 18 HOH C 375 HOH C 411
SITE 1 AC4 17 VAL D 17 GLU D 20 GLY D 21 ALA D 24
SITE 2 AC4 17 GLY D 26 THR D 27 GLY D 28 GLU D 29
SITE 3 AC4 17 LEU D 30 THR D 31 LYS D 112 TYR D 113
SITE 4 AC4 17 ARG D 140 HOH D 338 HOH D 339 HOH D 362
SITE 5 AC4 17 HOH D 409
CRYST1 67.358 83.213 278.147 90.00 90.00 90.00 P 21 21 21 16
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 0.014846 0.000000 0.000000 0.00000
SCALE2 0.000000 0.012017 0.000000 0.00000
SCALE3 0.000000 0.000000 0.003595 0.00000
(ATOM LINES ARE NOT SHOWN.)
END
