HEADER HYDROLASE 07-NOV-06 2NTA
TITLE CRYSTAL STRUCTURE OF PTP1B-INHIBITOR COMPLEX
COMPND MOL_ID: 1;
COMPND 2 MOLECULE: TYROSINE-PROTEIN PHOSPHATASE NON-RECEPTOR TYPE 1;
COMPND 3 CHAIN: A;
COMPND 4 FRAGMENT: CATALYTIC DOMAIN;
COMPND 5 SYNONYM: PROTEIN-TYROSINE PHOSPHATASE 1B, PTP-1B;
COMPND 6 EC: 3.1.3.48;
COMPND 7 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: PTPN1, PTP1B;
SOURCE 6 EXPRESSION_SYSTEM: ESCHERICHIA COLI;
SOURCE 7 EXPRESSION_SYSTEM_TAXID: 562
KEYWDS PTP1B, PROTEIN-INHIBITOR COMPLEX, HYDROLASE
EXPDTA X-RAY DIFFRACTION
AUTHOR W.XU,B.FOLLOWS
REVDAT 4 27-DEC-23 2NTA 1 REMARK SEQADV
REVDAT 3 24-FEB-09 2NTA 1 VERSN
REVDAT 2 05-JUN-07 2NTA 1 JRNL
REVDAT 1 17-APR-07 2NTA 0
JRNL AUTH Z.K.WAN,B.FOLLOWS,S.KIRINCICH,D.WILSON,E.BINNUN,W.XU,
JRNL AUTH 2 D.JOSEPH-MCCARTHY,J.WU,M.SMITH,Y.L.ZHANG,M.TAM,D.ERBE,S.TAM,
JRNL AUTH 3 E.SAIAH,J.LEE
JRNL TITL PROBING ACID REPLACEMENTS OF THIOPHENE PTP1B INHIBITORS.
JRNL REF BIOORG.MED.CHEM.LETT. V. 17 2913 2007
JRNL REFN ISSN 0960-894X
JRNL PMID 17336064
JRNL DOI 10.1016/J.BMCL.2007.02.043
REMARK 2
REMARK 2 RESOLUTION. 2.10 ANGSTROMS.
REMARK 3
REMARK 3 REFINEMENT.
REMARK 3 PROGRAM : CNS
REMARK 3 AUTHORS : BRUNGER,ADAMS,CLORE,DELANO,GROS,GROSSE-
REMARK 3 : KUNSTLEVE,JIANG,KUSZEWSKI,NILGES,PANNU,
REMARK 3 : READ,RICE,SIMONSON,WARREN
REMARK 3
REMARK 3 REFINEMENT TARGET : ENGH & HUBER
REMARK 3
REMARK 3 DATA USED IN REFINEMENT.
REMARK 3 RESOLUTION RANGE HIGH (ANGSTROMS) : 2.10
REMARK 3 RESOLUTION RANGE LOW (ANGSTROMS) : 20.00
REMARK 3 DATA CUTOFF (SIGMA(F)) : 0.000
REMARK 3 DATA CUTOFF HIGH (ABS(F)) : NULL
REMARK 3 DATA CUTOFF LOW (ABS(F)) : NULL
REMARK 3 COMPLETENESS (WORKING+TEST) (%) : 97.3
REMARK 3 NUMBER OF REFLECTIONS : 27071
REMARK 3
REMARK 3 FIT TO DATA USED IN REFINEMENT.
REMARK 3 CROSS-VALIDATION METHOD : NULL
REMARK 3 FREE R VALUE TEST SET SELECTION : RANDOM
REMARK 3 R VALUE (WORKING SET) : 0.215
REMARK 3 FREE R VALUE : 0.247
REMARK 3 FREE R VALUE TEST SET SIZE (%) : NULL
REMARK 3 FREE R VALUE TEST SET COUNT : 1347
REMARK 3 ESTIMATED ERROR OF FREE R VALUE : NULL
REMARK 3
REMARK 3 FIT IN THE HIGHEST RESOLUTION BIN.
REMARK 3 TOTAL NUMBER OF BINS USED : NULL
REMARK 3 BIN RESOLUTION RANGE HIGH (A) : NULL
REMARK 3 BIN RESOLUTION RANGE LOW (A) : NULL
REMARK 3 BIN COMPLETENESS (WORKING+TEST) (%) : NULL
REMARK 3 REFLECTIONS IN BIN (WORKING SET) : NULL
REMARK 3 BIN R VALUE (WORKING SET) : NULL
REMARK 3 BIN FREE R VALUE : NULL
REMARK 3 BIN FREE R VALUE TEST SET SIZE (%) : NULL
REMARK 3 BIN FREE R VALUE TEST SET COUNT : NULL
REMARK 3 ESTIMATED ERROR OF BIN FREE R VALUE : NULL
REMARK 3
REMARK 3 NUMBER OF NON-HYDROGEN ATOMS USED IN REFINEMENT.
REMARK 3 PROTEIN ATOMS : 2425
REMARK 3 NUCLEIC ACID ATOMS : 0
REMARK 3 HETEROGEN ATOMS : 20
REMARK 3 SOLVENT ATOMS : 218
REMARK 3
REMARK 3 B VALUES.
REMARK 3 FROM WILSON PLOT (A**2) : NULL
REMARK 3 MEAN B VALUE (OVERALL, A**2) : NULL
REMARK 3 OVERALL ANISOTROPIC B VALUE.
REMARK 3 B11 (A**2) : NULL
REMARK 3 B22 (A**2) : NULL
REMARK 3 B33 (A**2) : NULL
REMARK 3 B12 (A**2) : NULL
REMARK 3 B13 (A**2) : NULL
REMARK 3 B23 (A**2) : NULL
REMARK 3
REMARK 3 ESTIMATED COORDINATE ERROR.
REMARK 3 ESD FROM LUZZATI PLOT (A) : NULL
REMARK 3 ESD FROM SIGMAA (A) : NULL
REMARK 3 LOW RESOLUTION CUTOFF (A) : NULL
REMARK 3
REMARK 3 CROSS-VALIDATED ESTIMATED COORDINATE ERROR.
REMARK 3 ESD FROM C-V LUZZATI PLOT (A) : NULL
REMARK 3 ESD FROM C-V SIGMAA (A) : NULL
REMARK 3
REMARK 3 RMS DEVIATIONS FROM IDEAL VALUES.
REMARK 3 BOND LENGTHS (A) : 0.006
REMARK 3 BOND ANGLES (DEGREES) : 1.271
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 2NTA COMPLIES WITH FORMAT V. 3.30, 13-JUL-11
REMARK 100
REMARK 100 THIS ENTRY HAS BEEN PROCESSED BY RCSB ON 10-NOV-06.
REMARK 100 THE DEPOSITION ID IS D_1000040274.
REMARK 200
REMARK 200 EXPERIMENTAL DETAILS
REMARK 200 EXPERIMENT TYPE : X-RAY DIFFRACTION
REMARK 200 DATE OF DATA COLLECTION : 08-AUG-05
REMARK 200 TEMPERATURE (KELVIN) : 113
REMARK 200 PH : 7.0
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) : 1.5418
REMARK 200 MONOCHROMATOR : YALE MIRRORS
REMARK 200 OPTICS : MIRRORS
REMARK 200
REMARK 200 DETECTOR TYPE : AREA DETECTOR
REMARK 200 DETECTOR MANUFACTURER : SDMS
REMARK 200 INTENSITY-INTEGRATION SOFTWARE : HKL-2000
REMARK 200 DATA SCALING SOFTWARE : HKL-2000
REMARK 200
REMARK 200 NUMBER OF UNIQUE REFLECTIONS : 27099
REMARK 200 RESOLUTION RANGE HIGH (A) : 2.100
REMARK 200 RESOLUTION RANGE LOW (A) : 20.000
REMARK 200 REJECTION CRITERIA (SIGMA(I)) : 2.000
REMARK 200
REMARK 200 OVERALL.
REMARK 200 COMPLETENESS FOR RANGE (%) : 97.1
REMARK 200 DATA REDUNDANCY : 6.100
REMARK 200 R MERGE (I) : 0.11300
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) : 2.10
REMARK 200 HIGHEST RESOLUTION SHELL, RANGE LOW (A) : 2.18
REMARK 200 COMPLETENESS FOR SHELL (%) : 95.3
REMARK 200 DATA REDUNDANCY IN SHELL : 6.10
REMARK 200 R MERGE FOR SHELL (I) : 0.58700
REMARK 200 R SYM FOR SHELL (I) : NULL
REMARK 200 <I/SIGMA(I)> FOR SHELL : 3.190
REMARK 200
REMARK 200 DIFFRACTION PROTOCOL: SINGLE WAVELENGTH
REMARK 200 METHOD USED TO DETERMINE THE STRUCTURE: MOLECULAR REPLACEMENT
REMARK 200 SOFTWARE USED: CNS
REMARK 200 STARTING MODEL: NULL
REMARK 200
REMARK 200 REMARK: NULL
REMARK 280
REMARK 280 CRYSTAL
REMARK 280 SOLVENT CONTENT, VS (%): 63.42
REMARK 280 MATTHEWS COEFFICIENT, VM (ANGSTROMS**3/DA): 3.36
REMARK 280
REMARK 280 CRYSTALLIZATION CONDITIONS: 17% PEG 4000, 0.15M MGCL2, 0.1M HEPES,
REMARK 280 PH 7.0, VAPOR DIFFUSION, HANGING DROP, TEMPERATURE 278K
REMARK 290
REMARK 290 CRYSTALLOGRAPHIC SYMMETRY
REMARK 290 SYMMETRY OPERATORS FOR SPACE GROUP: P 31 2 1
REMARK 290
REMARK 290 SYMOP SYMMETRY
REMARK 290 NNNMMM OPERATOR
REMARK 290 1555 X,Y,Z
REMARK 290 2555 -Y,X-Y,Z+1/3
REMARK 290 3555 -X+Y,-X,Z+2/3
REMARK 290 4555 Y,X,-Z
REMARK 290 5555 X-Y,-Y,-Z+2/3
REMARK 290 6555 -X,-X+Y,-Z+1/3
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 -0.500000 -0.866025 0.000000 0.00000
REMARK 290 SMTRY2 2 0.866025 -0.500000 0.000000 0.00000
REMARK 290 SMTRY3 2 0.000000 0.000000 1.000000 34.72333
REMARK 290 SMTRY1 3 -0.500000 0.866025 0.000000 0.00000
REMARK 290 SMTRY2 3 -0.866025 -0.500000 0.000000 0.00000
REMARK 290 SMTRY3 3 0.000000 0.000000 1.000000 69.44667
REMARK 290 SMTRY1 4 -0.500000 0.866025 0.000000 0.00000
REMARK 290 SMTRY2 4 0.866025 0.500000 0.000000 0.00000
REMARK 290 SMTRY3 4 0.000000 0.000000 -1.000000 0.00000
REMARK 290 SMTRY1 5 1.000000 0.000000 0.000000 0.00000
REMARK 290 SMTRY2 5 0.000000 -1.000000 0.000000 0.00000
REMARK 290 SMTRY3 5 0.000000 0.000000 -1.000000 69.44667
REMARK 290 SMTRY1 6 -0.500000 -0.866025 0.000000 0.00000
REMARK 290 SMTRY2 6 -0.866025 0.500000 0.000000 0.00000
REMARK 290 SMTRY3 6 0.000000 0.000000 -1.000000 34.72333
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 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 MET A 1
REMARK 465 LEU A 299
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 CYS A 121 139.13 -170.84
REMARK 500 CYS A 215 -129.61 -132.43
REMARK 500 ILE A 219 -38.46 -138.65
REMARK 500 ILE A 261 112.73 78.70
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 521 A 301
REMARK 900
REMARK 900 RELATED ENTRIES
REMARK 900 RELATED ID: 2NT7 RELATED DB: PDB
REMARK 900 RELATED ID: 2HCX RELATED DB: PDB
REMARK 900 RELATED ID: 2HCE RELATED DB: PDB
REMARK 900 RELATED ID: 2HFA RELATED DB: PDB
DBREF 2NTA A 1 299 UNP P18031 PTN1_HUMAN 1 299
SEQADV 2NTA ASP A 252 UNP P18031 GLU 252 CONFLICT
SEQRES 1 A 299 MET GLU MET GLU LYS GLU PHE GLU GLN ILE ASP LYS SER
SEQRES 2 A 299 GLY SER TRP ALA ALA ILE TYR GLN ASP ILE ARG HIS GLU
SEQRES 3 A 299 ALA SER ASP PHE PRO CYS ARG VAL ALA LYS LEU PRO LYS
SEQRES 4 A 299 ASN LYS ASN ARG ASN ARG TYR ARG ASP VAL SER PRO PHE
SEQRES 5 A 299 ASP HIS SER ARG ILE LYS LEU HIS GLN GLU ASP ASN ASP
SEQRES 6 A 299 TYR ILE ASN ALA SER LEU ILE LYS MET GLU GLU ALA GLN
SEQRES 7 A 299 ARG SER TYR ILE LEU THR GLN GLY PRO LEU PRO ASN THR
SEQRES 8 A 299 CYS GLY HIS PHE TRP GLU MET VAL TRP GLU GLN LYS SER
SEQRES 9 A 299 ARG GLY VAL VAL MET LEU ASN ARG VAL MET GLU LYS GLY
SEQRES 10 A 299 SER LEU LYS CYS ALA GLN TYR TRP PRO GLN LYS GLU GLU
SEQRES 11 A 299 LYS GLU MET ILE PHE GLU ASP THR ASN LEU LYS LEU THR
SEQRES 12 A 299 LEU ILE SER GLU ASP ILE LYS SER TYR TYR THR VAL ARG
SEQRES 13 A 299 GLN LEU GLU LEU GLU ASN LEU THR THR GLN GLU THR ARG
SEQRES 14 A 299 GLU ILE LEU HIS PHE HIS TYR THR THR TRP PRO ASP PHE
SEQRES 15 A 299 GLY VAL PRO GLU SER PRO ALA SER PHE LEU ASN PHE LEU
SEQRES 16 A 299 PHE LYS VAL ARG GLU SER GLY SER LEU SER PRO GLU HIS
SEQRES 17 A 299 GLY PRO VAL VAL VAL HIS CYS SER ALA GLY ILE GLY ARG
SEQRES 18 A 299 SER GLY THR PHE CYS LEU ALA ASP THR CYS LEU LEU LEU
SEQRES 19 A 299 MET ASP LYS ARG LYS ASP PRO SER SER VAL ASP ILE LYS
SEQRES 20 A 299 LYS VAL LEU LEU ASP MET ARG LYS PHE ARG MET GLY LEU
SEQRES 21 A 299 ILE GLN THR ALA ASP GLN LEU ARG PHE SER TYR LEU ALA
SEQRES 22 A 299 VAL ILE GLU GLY ALA LYS PHE ILE MET GLY ASP SER SER
SEQRES 23 A 299 VAL GLN ASP GLN TRP LYS GLU LEU SER HIS GLU ASP LEU
HET 521 A 301 20
HETNAM 521 5-(4-CHLORO-5-PHENYL-3-THIENYL)-1,2,5-THIADIAZOLIDIN-3-
HETNAM 2 521 ONE 1,1-DIOXIDE
FORMUL 2 521 C12 H9 CL N2 O3 S2
FORMUL 3 HOH *218(H2 O)
HELIX 1 1 GLU A 2 SER A 13 1 12
HELIX 2 2 SER A 15 ALA A 27 1 13
HELIX 3 3 CYS A 32 LEU A 37 1 6
HELIX 4 4 PRO A 38 ASN A 44 5 7
HELIX 5 5 THR A 91 GLN A 102 1 12
HELIX 6 6 SER A 187 SER A 201 1 15
HELIX 7 7 ILE A 219 LYS A 239 1 21
HELIX 8 8 ASP A 240 VAL A 244 5 5
HELIX 9 9 ASP A 245 ARG A 254 1 10
HELIX 10 10 THR A 263 MET A 282 1 20
HELIX 11 11 SER A 285 HIS A 296 1 12
SHEET 1 A 9 ARG A 56 LYS A 58 0
SHEET 2 A 9 TYR A 66 MET A 74 -1 O ALA A 69 N ILE A 57
SHEET 3 A 9 ARG A 79 THR A 84 -1 O TYR A 81 N ILE A 72
SHEET 4 A 9 VAL A 211 HIS A 214 1 O VAL A 213 N ILE A 82
SHEET 5 A 9 GLY A 106 MET A 109 1 N VAL A 108 O VAL A 212
SHEET 6 A 9 THR A 168 TYR A 176 1 O TYR A 176 N MET A 109
SHEET 7 A 9 TYR A 153 ASN A 162 -1 N THR A 154 O HIS A 175
SHEET 8 A 9 LEU A 140 ILE A 149 -1 N LYS A 141 O GLU A 161
SHEET 9 A 9 MET A 133 PHE A 135 -1 N MET A 133 O LEU A 142
SHEET 1 B 2 MET A 114 GLU A 115 0
SHEET 2 B 2 SER A 118 LEU A 119 -1 O SER A 118 N GLU A 115
SITE 1 AC1 12 TYR A 46 ASP A 181 PHE A 182 CYS A 215
SITE 2 AC1 12 SER A 216 ALA A 217 GLY A 218 ILE A 219
SITE 3 AC1 12 GLY A 220 ARG A 221 GLN A 262 GLN A 266
CRYST1 88.256 88.256 104.170 90.00 90.00 120.00 P 31 2 1 6
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 0.011331 0.006542 0.000000 0.00000
SCALE2 0.000000 0.013084 0.000000 0.00000
SCALE3 0.000000 0.000000 0.009600 0.00000
(ATOM LINES ARE NOT SHOWN.)
END
