HEADER TRANSFERASE 21-JUL-07 2Z60
TITLE CRYSTAL STRUCTURE OF THE T315I MUTANT OF ABL KINASE BOUND WITH PPY-A
COMPND MOL_ID: 1;
COMPND 2 MOLECULE: PROTO-ONCOGENE TYROSINE-PROTEIN KINASE ABL1;
COMPND 3 CHAIN: A;
COMPND 4 FRAGMENT: RESIDUES 228-511;
COMPND 5 SYNONYM: P150, C-ABL, ABELSON MURINE LEUKEMIA VIRAL ONCOGENE HOMOLOG
COMPND 6 1, ABL KINASE;
COMPND 7 EC: 2.7.10.2;
COMPND 8 ENGINEERED: YES;
COMPND 9 MUTATION: YES
SOURCE MOL_ID: 1;
SOURCE 2 ORGANISM_SCIENTIFIC: MUS MUSCULUS;
SOURCE 3 ORGANISM_COMMON: HOUSE MOUSE;
SOURCE 4 ORGANISM_TAXID: 10090;
SOURCE 5 EXPRESSION_SYSTEM: ESCHERICHIA COLI BL21(DE3);
SOURCE 6 EXPRESSION_SYSTEM_TAXID: 469008;
SOURCE 7 EXPRESSION_SYSTEM_STRAIN: BL21 DE3;
SOURCE 8 EXPRESSION_SYSTEM_VECTOR_TYPE: PLASMID;
SOURCE 9 EXPRESSION_SYSTEM_PLASMID: PET28A
KEYWDS ABL, KINASE, MUTANT, T315I, ALTERNATIVE SPLICING, ATP-BINDING, CELL
KEYWDS 2 ADHESION, CHROMOSOMAL REARRANGEMENT, CYTOPLASM, CYTOSKELETON,
KEYWDS 3 LIPOPROTEIN, MAGNESIUM, MANGANESE, METAL-BINDING, MYRISTATE,
KEYWDS 4 NUCLEOTIDE-BINDING, NUCLEUS, PHOSPHORYLATION, PROTO-ONCOGENE, SH2
KEYWDS 5 DOMAIN, SH3 DOMAIN, TRANSFERASE
EXPDTA X-RAY DIFFRACTION
AUTHOR T.ZHOU,D.DALGARNO,X.ZHU
REVDAT 4 01-NOV-23 2Z60 1 REMARK
REVDAT 3 10-NOV-21 2Z60 1 REMARK SEQADV
REVDAT 2 24-FEB-09 2Z60 1 VERSN
REVDAT 1 18-SEP-07 2Z60 0
JRNL AUTH T.ZHOU,L.PARILLON,F.LI,Y.WANG,J.KEATS,S.LAMORE,Q.XU,
JRNL AUTH 2 W.SHAKESPEARE,D.DALGARNO,X.ZHU
JRNL TITL CRYSTAL STRUCTURE OF THE T315I MUTANT OF ABL KINASE
JRNL REF CHEM.BIOL.DRUG DES. V. 70 171 2007
JRNL REFN ISSN 1747-0277
JRNL PMID 17718712
JRNL DOI 10.1111/J.1747-0285.2007.00556.X
REMARK 2
REMARK 2 RESOLUTION. 1.95 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 : NULL
REMARK 3
REMARK 3 DATA USED IN REFINEMENT.
REMARK 3 RESOLUTION RANGE HIGH (ANGSTROMS) : 1.95
REMARK 3 RESOLUTION RANGE LOW (ANGSTROMS) : 50.00
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) (%) : 99.0
REMARK 3 NUMBER OF REFLECTIONS : 25260
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 SET) : 0.206
REMARK 3 FREE R VALUE : 0.245
REMARK 3 FREE R VALUE TEST SET SIZE (%) : NULL
REMARK 3 FREE R VALUE TEST SET COUNT : NULL
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 : 2280
REMARK 3 NUCLEIC ACID ATOMS : 0
REMARK 3 HETEROGEN ATOMS : 28
REMARK 3 SOLVENT ATOMS : 168
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 2Z60 COMPLIES WITH FORMAT V. 3.30, 13-JUL-11
REMARK 100
REMARK 100 THIS ENTRY HAS BEEN PROCESSED BY PDBJ ON 31-JUL-07.
REMARK 100 THE DEPOSITION ID IS D_1000027564.
REMARK 200
REMARK 200 EXPERIMENTAL DETAILS
REMARK 200 EXPERIMENT TYPE : X-RAY DIFFRACTION
REMARK 200 DATE OF DATA COLLECTION : 11-NOV-06
REMARK 200 TEMPERATURE (KELVIN) : 100
REMARK 200 PH : 8.5
REMARK 200 NUMBER OF CRYSTALS USED : 1
REMARK 200
REMARK 200 SYNCHROTRON (Y/N) : Y
REMARK 200 RADIATION SOURCE : APS
REMARK 200 BEAMLINE : 19-BM
REMARK 200 X-RAY GENERATOR MODEL : NULL
REMARK 200 MONOCHROMATIC OR LAUE (M/L) : M
REMARK 200 WAVELENGTH OR RANGE (A) : 0.98
REMARK 200 MONOCHROMATOR : NULL
REMARK 200 OPTICS : NULL
REMARK 200
REMARK 200 DETECTOR TYPE : CCD
REMARK 200 DETECTOR MANUFACTURER : ADSC QUANTUM 315
REMARK 200 INTENSITY-INTEGRATION SOFTWARE : DENZO
REMARK 200 DATA SCALING SOFTWARE : HKL-2000
REMARK 200
REMARK 200 NUMBER OF UNIQUE REFLECTIONS : 25260
REMARK 200 RESOLUTION RANGE HIGH (A) : 1.950
REMARK 200 RESOLUTION RANGE LOW (A) : 50.000
REMARK 200 REJECTION CRITERIA (SIGMA(I)) : 0.000
REMARK 200
REMARK 200 OVERALL.
REMARK 200 COMPLETENESS FOR RANGE (%) : 99.3
REMARK 200 DATA REDUNDANCY : 17.00
REMARK 200 R MERGE (I) : 0.05700
REMARK 200 R SYM (I) : 0.05700
REMARK 200 <I/SIGMA(I)> FOR THE DATA SET : 21.0000
REMARK 200
REMARK 200 IN THE HIGHEST RESOLUTION SHELL.
REMARK 200 HIGHEST RESOLUTION SHELL, RANGE HIGH (A) : 1.95
REMARK 200 HIGHEST RESOLUTION SHELL, RANGE LOW (A) : 2.02
REMARK 200 COMPLETENESS FOR SHELL (%) : 97.0
REMARK 200 DATA REDUNDANCY IN SHELL : 4.00
REMARK 200 R MERGE FOR SHELL (I) : 0.37000
REMARK 200 R SYM FOR SHELL (I) : 0.37000
REMARK 200 <I/SIGMA(I)> FOR SHELL : 2.900
REMARK 200
REMARK 200 DIFFRACTION PROTOCOL: SINGLE WAVELENGTH
REMARK 200 METHOD USED TO DETERMINE THE STRUCTURE: MOLECULAR REPLACEMENT
REMARK 200 SOFTWARE USED: AMORE
REMARK 200 STARTING MODEL: 2GQG
REMARK 200
REMARK 200 REMARK: NULL
REMARK 280
REMARK 280 CRYSTAL
REMARK 280 SOLVENT CONTENT, VS (%): 51.62
REMARK 280 MATTHEWS COEFFICIENT, VM (ANGSTROMS**3/DA): 2.54
REMARK 280
REMARK 280 CRYSTALLIZATION CONDITIONS: 30% PEG 4K, 0.1M TRIS, 0.2M SODIUM
REMARK 280 ACETATE, PH 8.5, EVAPORATION, TEMPERATURE 277K
REMARK 290
REMARK 290 CRYSTALLOGRAPHIC SYMMETRY
REMARK 290 SYMMETRY OPERATORS FOR SPACE GROUP: P 1 21 1
REMARK 290
REMARK 290 SYMOP SYMMETRY
REMARK 290 NNNMMM OPERATOR
REMARK 290 1555 X,Y,Z
REMARK 290 2555 -X,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 29.64000
REMARK 290 SMTRY3 2 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 ASP A 276
REMARK 465 THR A 277
REMARK 465 MET A 278
REMARK 465 LYS A 512
REMARK 465 ARG A 513
REMARK 465 GLY A 514
REMARK 465 THR A 515
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 LYS A 245 -77.15 -109.11
REMARK 500 ASP A 363 43.62 -151.37
REMARK 500 ASP A 381 81.83 59.64
REMARK 500 PRO A 402 96.21 -62.25
REMARK 500 ASP A 455 18.34 80.84
REMARK 500 GLU A 509 49.09 -85.11
REMARK 500 LEU A 510 -43.22 -134.60
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 P3Y A 1
REMARK 900
REMARK 900 RELATED ENTRIES
REMARK 900 RELATED ID: 2QOH RELATED DB: PDB
DBREF 2Z60 A 229 515 UNP P00520 ABL1_MOUSE 229 515
SEQADV 2Z60 GLY A 228 UNP P00520 EXPRESSION TAG
SEQADV 2Z60 ILE A 315 UNP P00520 THR 315 ENGINEERED MUTATION
SEQRES 1 A 288 GLY SER PRO ASN TYR ASP LYS TRP GLU MET GLU ARG THR
SEQRES 2 A 288 ASP ILE THR MET LYS HIS LYS LEU GLY GLY GLY GLN TYR
SEQRES 3 A 288 GLY GLU VAL TYR GLU GLY VAL TRP LYS LYS TYR SER LEU
SEQRES 4 A 288 THR VAL ALA VAL LYS THR LEU LYS GLU ASP THR MET GLU
SEQRES 5 A 288 VAL GLU GLU PHE LEU LYS GLU ALA ALA VAL MET LYS GLU
SEQRES 6 A 288 ILE LYS HIS PRO ASN LEU VAL GLN LEU LEU GLY VAL CYS
SEQRES 7 A 288 THR ARG GLU PRO PRO PHE TYR ILE ILE ILE GLU PHE MET
SEQRES 8 A 288 THR TYR GLY ASN LEU LEU ASP TYR LEU ARG GLU CYS ASN
SEQRES 9 A 288 ARG GLN GLU VAL SER ALA VAL VAL LEU LEU TYR MET ALA
SEQRES 10 A 288 THR GLN ILE SER SER ALA MET GLU TYR LEU GLU LYS LYS
SEQRES 11 A 288 ASN PHE ILE HIS ARG ASP LEU ALA ALA ARG ASN CYS LEU
SEQRES 12 A 288 VAL GLY GLU ASN HIS LEU VAL LYS VAL ALA ASP PHE GLY
SEQRES 13 A 288 LEU SER ARG LEU MET THR GLY ASP THR TYR THR ALA HIS
SEQRES 14 A 288 ALA GLY ALA LYS PHE PRO ILE LYS TRP THR ALA PRO GLU
SEQRES 15 A 288 SER LEU ALA TYR ASN LYS PHE SER ILE LYS SER ASP VAL
SEQRES 16 A 288 TRP ALA PHE GLY VAL LEU LEU TRP GLU ILE ALA THR TYR
SEQRES 17 A 288 GLY MET SER PRO TYR PRO GLY ILE ASP LEU SER GLN VAL
SEQRES 18 A 288 TYR GLU LEU LEU GLU LYS ASP TYR ARG MET GLU ARG PRO
SEQRES 19 A 288 GLU GLY CYS PRO GLU LYS VAL TYR GLU LEU MET ARG ALA
SEQRES 20 A 288 CYS TRP GLN TRP ASN PRO SER ASP ARG PRO SER PHE ALA
SEQRES 21 A 288 GLU ILE HIS GLN ALA PHE GLU THR MET PHE GLN GLU SER
SEQRES 22 A 288 SER ILE SER ASP GLU VAL GLU LYS GLU LEU GLY LYS ARG
SEQRES 23 A 288 GLY THR
HET P3Y A 1 28
HETNAM P3Y 5-[3-(2-METHOXYPHENYL)-1H-PYRROLO[2,3-B]PYRIDIN-5-YL]-
HETNAM 2 P3Y N,N-DIMETHYLPYRIDINE-3-CARBOXAMIDE
FORMUL 2 P3Y C22 H20 N4 O2
FORMUL 3 HOH *168(H2 O)
HELIX 1 1 GLU A 238 THR A 240 5 3
HELIX 2 2 GLY A 249 GLN A 252 5 4
HELIX 3 3 LYS A 263 SER A 265 5 3
HELIX 4 4 GLU A 279 ILE A 293 1 15
HELIX 5 5 ASN A 322 CYS A 330 1 9
HELIX 6 6 SER A 336 LYS A 357 1 22
HELIX 7 7 ALA A 365 ARG A 367 5 3
HELIX 8 8 GLU A 373 HIS A 375 5 3
HELIX 9 9 PRO A 402 THR A 406 5 5
HELIX 10 10 ALA A 407 ASN A 414 1 8
HELIX 11 11 SER A 417 THR A 434 1 18
HELIX 12 12 GLN A 447 LYS A 454 1 8
HELIX 13 13 PRO A 465 TRP A 476 1 12
HELIX 14 14 ASN A 479 ARG A 483 5 5
HELIX 15 15 SER A 485 GLU A 509 1 25
SHEET 1 A 5 ILE A 242 LYS A 247 0
SHEET 2 A 5 VAL A 256 TRP A 261 -1 O GLU A 258 N HIS A 246
SHEET 3 A 5 LEU A 266 THR A 272 -1 O LEU A 266 N TRP A 261
SHEET 4 A 5 TYR A 312 GLU A 316 -1 O ILE A 315 N ALA A 269
SHEET 5 A 5 LEU A 301 CYS A 305 -1 N LEU A 302 O ILE A 314
SHEET 1 B 2 PHE A 359 ILE A 360 0
SHEET 2 B 2 ARG A 386 LEU A 387 -1 O ARG A 386 N ILE A 360
SHEET 1 C 2 CYS A 369 VAL A 371 0
SHEET 2 C 2 VAL A 377 VAL A 379 -1 O LYS A 378 N LEU A 370
SHEET 1 D 2 TYR A 393 THR A 394 0
SHEET 2 D 2 LYS A 415 PHE A 416 -1 O PHE A 416 N TYR A 393
CISPEP 1 PRO A 309 PRO A 310 0 0.07
SITE 1 AC1 11 GLY A 249 TYR A 253 ALA A 269 GLU A 316
SITE 2 AC1 11 PHE A 317 MET A 318 THR A 319 GLY A 321
SITE 3 AC1 11 ASN A 322 ARG A 367 LEU A 370
CRYST1 43.035 59.280 66.520 90.00 94.88 90.00 P 1 21 1 2
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 0.023237 0.000000 0.001984 0.00000
SCALE2 0.000000 0.016869 0.000000 0.00000
SCALE3 0.000000 0.000000 0.015088 0.00000
(ATOM LINES ARE NOT SHOWN.)
END
