HEADER TRANSFERASE 01-FEB-12 4AGW
TITLE DISCOVERY OF A SMALL MOLECULE TYPE II INHIBITOR OF WILD-TYPE AND
TITLE 2 GATEKEEPER MUTANTS OF BCR-ABL, PDGFRALPHA, KIT, AND SRC KINASES
COMPND MOL_ID: 1;
COMPND 2 MOLECULE: PROTO-ONCOGENE TYROSINE-PROTEIN KINASE SRC;
COMPND 3 CHAIN: A, B;
COMPND 4 FRAGMENT: KINASE DOMAIN, RESIDUES 251-533;
COMPND 5 SYNONYM: SRC KINASE, PROTO-ONCOGENE C-SRC, PP60C-SRC, P60-SRC;
COMPND 6 EC: 2.7.10.2;
COMPND 7 ENGINEERED: YES
SOURCE MOL_ID: 1;
SOURCE 2 ORGANISM_SCIENTIFIC: GALLUS GALLUS;
SOURCE 3 ORGANISM_TAXID: 9031;
SOURCE 4 EXPRESSION_SYSTEM: ESCHERICHIA COLI;
SOURCE 5 EXPRESSION_SYSTEM_TAXID: 562
KEYWDS ATP-BINDING, LIPOPROTEIN, MYRISTATE, PHOSPHOPROTEIN, SH2 DOMAIN, SH3
KEYWDS 2 DOMAIN, TRANSFERASE
EXPDTA X-RAY DIFFRACTION
AUTHOR E.WEISBERG,H.G.CHOI,M.SEELIGER,N.GRAY,J.D.GRIFFIN
REVDAT 3 28-APR-21 4AGW 1 COMPND REMARK HETNAM
REVDAT 2 27-FEB-19 4AGW 1 REMARK
REVDAT 1 15-FEB-12 4AGW 0
JRNL AUTH E.WEISBERG,H.G.CHOI,A.RAY,R.BARRETT,J.ZHANG,T.SIM,W.ZHOU,
JRNL AUTH 2 M.SEELIGER,M.CAMERON,M.AZAM,J.A.FLETCHER,M.DEBIEC-RYCHTER,
JRNL AUTH 3 M.MAYEDA,D.MORENO,A.L.KUNG,P.A.JANNE,R.KHOSRAVI-FAR,
JRNL AUTH 4 J.V.MELO,P.W.MANLEY,S.ADAMIA,C.WU,N.GRAY,J.D.GRIFFIN
JRNL TITL DISCOVERY OF A SMALL-MOLECULE TYPE II INHIBITOR OF WILD-TYPE
JRNL TITL 2 AND GATEKEEPER MUTANTS OF BCR-ABL, PDGFRALPHA, KIT, AND SRC
JRNL TITL 3 KINASES: NOVEL TYPE II INHIBITOR OF GATEKEEPER MUTANTS.
JRNL REF BLOOD V. 115 4206 2010
JRNL REFN ISSN 0006-4971
JRNL PMID 20299508
JRNL DOI 10.1182/BLOOD-2009-11-251751
REMARK 2
REMARK 2 RESOLUTION. 2.60 ANGSTROMS.
REMARK 3
REMARK 3 REFINEMENT.
REMARK 3 PROGRAM : PHENIX (PHENIX.REFINE)
REMARK 3 AUTHORS : PAUL ADAMS,PAVEL AFONINE,VINCENT CHEN,IAN
REMARK 3 : DAVIS,KRESHNA GOPAL,RALF GROSSE-KUNSTLEVE,
REMARK 3 : LI-WEI HUNG,ROBERT IMMORMINO,TOM IOERGER,
REMARK 3 : AIRLIE MCCOY,ERIK MCKEE,NIGEL MORIARTY,
REMARK 3 : REETAL PAI,RANDY READ,JANE RICHARDSON,
REMARK 3 : DAVID RICHARDSON,TOD ROMO,JIM SACCHETTINI,
REMARK 3 : NICHOLAS SAUTER,JACOB SMITH,LAURENT
REMARK 3 : STORONI,TOM TERWILLIGER,PETER ZWART
REMARK 3
REMARK 3 REFINEMENT TARGET : ML
REMARK 3
REMARK 3 DATA USED IN REFINEMENT.
REMARK 3 RESOLUTION RANGE HIGH (ANGSTROMS) : 2.60
REMARK 3 RESOLUTION RANGE LOW (ANGSTROMS) : 42.27
REMARK 3 MIN(FOBS/SIGMA_FOBS) : 0.100
REMARK 3 COMPLETENESS FOR RANGE (%) : 92.2
REMARK 3 NUMBER OF REFLECTIONS : 19430
REMARK 3
REMARK 3 FIT TO DATA USED IN REFINEMENT.
REMARK 3 R VALUE (WORKING + TEST SET) : 0.230
REMARK 3 R VALUE (WORKING SET) : 0.226
REMARK 3 FREE R VALUE : 0.271
REMARK 3 FREE R VALUE TEST SET SIZE (%) : 8.000
REMARK 3 FREE R VALUE TEST SET COUNT : 1547
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 42.2727 - 5.7780 0.99 1743 148 0.2180 0.2455
REMARK 3 2 5.7780 - 4.5879 0.98 1710 155 0.2115 0.2728
REMARK 3 3 4.5879 - 4.0085 0.97 1736 147 0.1871 0.2203
REMARK 3 4 4.0085 - 3.6422 0.97 1697 149 0.2164 0.2495
REMARK 3 5 3.6422 - 3.3813 0.96 1669 154 0.2261 0.2651
REMARK 3 6 3.3813 - 3.1820 0.93 1645 139 0.2256 0.2826
REMARK 3 7 3.1820 - 3.0227 0.93 1662 142 0.2230 0.2919
REMARK 3 8 3.0227 - 2.8912 0.91 1567 139 0.2376 0.2785
REMARK 3 9 2.8912 - 2.7799 0.87 1557 125 0.2532 0.3060
REMARK 3 10 2.7799 - 2.6840 0.83 1444 127 0.2704 0.3573
REMARK 3 11 2.6840 - 2.6001 0.81 1453 122 0.2790 0.3235
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 : 0.33
REMARK 3 B_SOL : 30.26
REMARK 3
REMARK 3 ERROR ESTIMATES.
REMARK 3 COORDINATE ERROR (MAXIMUM-LIKELIHOOD BASED) : 0.420
REMARK 3 PHASE ERROR (DEGREES, MAXIMUM-LIKELIHOOD BASED) : 29.290
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) : -8.27690
REMARK 3 B22 (A**2) : -3.56870
REMARK 3 B33 (A**2) : 11.84560
REMARK 3 B12 (A**2) : -0.14090
REMARK 3 B13 (A**2) : -0.05180
REMARK 3 B23 (A**2) : 7.21380
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 : 0.010 4378
REMARK 3 ANGLE : 1.570 5938
REMARK 3 CHIRALITY : 0.132 621
REMARK 3 PLANARITY : 0.011 755
REMARK 3 DIHEDRAL : 18.715 1689
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 : 1
REMARK 3 NCS GROUP : 1
REMARK 3 NCS OPERATOR : 1
REMARK 3 REFERENCE SELECTION: CHAIN A AND (RESSEQ 335:405 OR RESSEQ
REMARK 3 425:533 )
REMARK 3 SELECTION : CHAIN B AND (RESSEQ 335:405 OR RESSEQ
REMARK 3 425:533 )
REMARK 3 ATOM PAIRS NUMBER : 1457
REMARK 3 RMSD : 0.088
REMARK 3
REMARK 3 OTHER REFINEMENT REMARKS: NULL
REMARK 4
REMARK 4 4AGW COMPLIES WITH FORMAT V. 3.30, 13-JUL-11
REMARK 100
REMARK 100 THIS ENTRY HAS BEEN PROCESSED BY PDBE ON 01-FEB-12.
REMARK 100 THE DEPOSITION ID IS D_1290051123.
REMARK 200
REMARK 200 EXPERIMENTAL DETAILS
REMARK 200 EXPERIMENT TYPE : X-RAY DIFFRACTION
REMARK 200 DATE OF DATA COLLECTION : 24-APR-09
REMARK 200 TEMPERATURE (KELVIN) : 100
REMARK 200 PH : NULL
REMARK 200 NUMBER OF CRYSTALS USED : 1
REMARK 200
REMARK 200 SYNCHROTRON (Y/N) : Y
REMARK 200 RADIATION SOURCE : ALS
REMARK 200 BEAMLINE : 8.2.1
REMARK 200 X-RAY GENERATOR MODEL : NULL
REMARK 200 MONOCHROMATIC OR LAUE (M/L) : M
REMARK 200 WAVELENGTH OR RANGE (A) : 1
REMARK 200 MONOCHROMATOR : NULL
REMARK 200 OPTICS : NULL
REMARK 200
REMARK 200 DETECTOR TYPE : CCD
REMARK 200 DETECTOR MANUFACTURER : ADSC QUANTUM 315R
REMARK 200 INTENSITY-INTEGRATION SOFTWARE : HKL-2000
REMARK 200 DATA SCALING SOFTWARE : SCALEPACK
REMARK 200
REMARK 200 NUMBER OF UNIQUE REFLECTIONS : 19430
REMARK 200 RESOLUTION RANGE HIGH (A) : 2.500
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 (%) : 93.4
REMARK 200 DATA REDUNDANCY : NULL
REMARK 200 R MERGE (I) : 0.11000
REMARK 200 R SYM (I) : NULL
REMARK 200 <I/SIGMA(I)> FOR THE DATA SET : 7.2000
REMARK 200
REMARK 200 IN THE HIGHEST RESOLUTION SHELL.
REMARK 200 HIGHEST RESOLUTION SHELL, RANGE HIGH (A) : NULL
REMARK 200 HIGHEST RESOLUTION SHELL, RANGE LOW (A) : NULL
REMARK 200 COMPLETENESS FOR SHELL (%) : NULL
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: OTHER
REMARK 200 SOFTWARE USED: NULL
REMARK 200 STARTING MODEL: NONE
REMARK 200
REMARK 200 REMARK: NONE
REMARK 280
REMARK 280 CRYSTAL
REMARK 280 SOLVENT CONTENT, VS (%): 54.42
REMARK 280 MATTHEWS COEFFICIENT, VM (ANGSTROMS**3/DA): 2.70
REMARK 280
REMARK 280 CRYSTALLIZATION CONDITIONS: PROTEIN CONCENTRATION 0.3 MM INHIBITOR
REMARK 280 CONCENTRATION 0.5 MM METHOD HANGING DROP VAPOR DIFFUSION AT 298
REMARK 280 K PROTEIN BUFFER 5 % DMSO, 20 MM TRIS PH 8.0, 250 MM NACL, 5 %
REMARK 280 GLYCEROL, 1 MM DTT. MOTHER LIQUOR: 100 MM MES PH 6.5, 7.5 % PEG
REMARK 280 3350, 10 % GLYCEROL, 1 MM DTT, VAPOR DIFFUSION, HANGING DROP
REMARK 290
REMARK 290 CRYSTALLOGRAPHIC SYMMETRY
REMARK 290 SYMMETRY OPERATORS FOR SPACE GROUP: P 1
REMARK 290
REMARK 290 SYMOP SYMMETRY
REMARK 290 NNNMMM OPERATOR
REMARK 290 1555 X,Y,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
REMARK 290 REMARK: NULL
REMARK 300
REMARK 300 BIOMOLECULE: 1, 2
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 350
REMARK 350 BIOMOLECULE: 2
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: B
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 GLY A 248
REMARK 465 HIS A 249
REMARK 465 MET A 250
REMARK 465 GLN A 251
REMARK 465 THR A 252
REMARK 465 GLN A 253
REMARK 465 GLY A 254
REMARK 465 LEU A 255
REMARK 465 ALA A 256
REMARK 465 GLY A 406
REMARK 465 LEU A 407
REMARK 465 ALA A 408
REMARK 465 ARG A 409
REMARK 465 LEU A 410
REMARK 465 ILE A 411
REMARK 465 GLU A 412
REMARK 465 ASP A 413
REMARK 465 ASN A 414
REMARK 465 GLU A 415
REMARK 465 TYR A 416
REMARK 465 THR A 417
REMARK 465 ALA A 418
REMARK 465 ARG A 419
REMARK 465 GLN A 420
REMARK 465 GLY A 421
REMARK 465 ALA A 422
REMARK 465 LYS A 423
REMARK 465 PHE A 424
REMARK 465 GLY B 248
REMARK 465 HIS B 249
REMARK 465 MET B 250
REMARK 465 GLN B 251
REMARK 465 THR B 252
REMARK 465 GLN B 253
REMARK 465 GLY B 254
REMARK 465 LEU B 255
REMARK 465 ALA B 256
REMARK 465 LYS B 257
REMARK 465 GLY B 406
REMARK 465 LEU B 407
REMARK 465 ALA B 408
REMARK 465 ARG B 409
REMARK 465 LEU B 410
REMARK 465 ILE B 411
REMARK 465 GLU B 412
REMARK 465 ASP B 413
REMARK 465 ASN B 414
REMARK 465 GLU B 415
REMARK 465 TYR B 416
REMARK 465 THR B 417
REMARK 465 ALA B 418
REMARK 465 ARG B 419
REMARK 465 GLN B 420
REMARK 465 GLY B 421
REMARK 465 ALA B 422
REMARK 465 LYS B 423
REMARK 465 PHE B 424
REMARK 500
REMARK 500 GEOMETRY AND STEREOCHEMISTRY
REMARK 500 SUBTOPIC: CLOSE CONTACTS IN SAME ASYMMETRIC UNIT
REMARK 500
REMARK 500 THE FOLLOWING ATOMS ARE IN CLOSE CONTACT.
REMARK 500
REMARK 500 ATM1 RES C SSEQI ATM2 RES C SSEQI DISTANCE
REMARK 500 NE ARG A 460 OD2 ASP B 518 1.95
REMARK 500 OE1 GLU A 486 O HOH A 2060 2.11
REMARK 500 O PHE A 515 O HOH A 2066 2.15
REMARK 500 NH1 ARG A 477 O HOH A 2049 2.17
REMARK 500 OG SER B 522 O HOH A 2041 2.18
REMARK 500
REMARK 500 REMARK: NULL
REMARK 500
REMARK 500 GEOMETRY AND STEREOCHEMISTRY
REMARK 500 SUBTOPIC: COVALENT BOND ANGLES
REMARK 500
REMARK 500 THE STEREOCHEMICAL PARAMETERS OF THE FOLLOWING RESIDUES
REMARK 500 HAVE VALUES WHICH DEVIATE FROM EXPECTED VALUES BY MORE
REMARK 500 THAN 6*RMSD (M=MODEL NUMBER; RES=RESIDUE NAME; C=CHAIN
REMARK 500 IDENTIFIER; SSEQ=SEQUENCE NUMBER; I=INSERTION CODE).
REMARK 500
REMARK 500 STANDARD TABLE:
REMARK 500 FORMAT: (10X,I3,1X,A3,1X,A1,I4,A1,3(1X,A4,2X),12X,F5.1)
REMARK 500
REMARK 500 EXPECTED VALUES PROTEIN: ENGH AND HUBER, 1999
REMARK 500 EXPECTED VALUES NUCLEIC ACID: CLOWNEY ET AL 1996
REMARK 500
REMARK 500 M RES CSSEQI ATM1 ATM2 ATM3
REMARK 500 ARG A 359 CD - NE - CZ ANGL. DEV. = 8.9 DEGREES
REMARK 500 ARG A 359 NE - CZ - NH1 ANGL. DEV. = 6.7 DEGREES
REMARK 500 ARG A 359 NE - CZ - NH2 ANGL. DEV. = -6.7 DEGREES
REMARK 500 ARG A 379 CD - NE - CZ ANGL. DEV. = 9.6 DEGREES
REMARK 500 ARG A 379 NE - CZ - NH1 ANGL. DEV. = 6.6 DEGREES
REMARK 500 ARG A 379 NE - CZ - NH2 ANGL. DEV. = -6.8 DEGREES
REMARK 500 ARG A 385 NE - CZ - NH1 ANGL. DEV. = 5.5 DEGREES
REMARK 500 ARG A 385 NE - CZ - NH2 ANGL. DEV. = -5.8 DEGREES
REMARK 500 ARG A 388 NE - CZ - NH1 ANGL. DEV. = 6.5 DEGREES
REMARK 500 ARG A 388 NE - CZ - NH2 ANGL. DEV. = -6.6 DEGREES
REMARK 500 ARG A 506 NE - CZ - NH1 ANGL. DEV. = 4.8 DEGREES
REMARK 500 ARG A 506 NE - CZ - NH2 ANGL. DEV. = -5.6 DEGREES
REMARK 500 ARG B 359 CD - NE - CZ ANGL. DEV. = 8.6 DEGREES
REMARK 500 ARG B 359 NE - CZ - NH1 ANGL. DEV. = 5.8 DEGREES
REMARK 500 ARG B 359 NE - CZ - NH2 ANGL. DEV. = -6.4 DEGREES
REMARK 500 ARG B 379 CD - NE - CZ ANGL. DEV. = 8.4 DEGREES
REMARK 500 ARG B 379 NE - CZ - NH1 ANGL. DEV. = 5.9 DEGREES
REMARK 500 ARG B 379 NE - CZ - NH2 ANGL. DEV. = -5.9 DEGREES
REMARK 500 ARG B 385 NE - CZ - NH1 ANGL. DEV. = 5.5 DEGREES
REMARK 500 ARG B 385 NE - CZ - NH2 ANGL. DEV. = -6.5 DEGREES
REMARK 500 ARG B 388 NE - CZ - NH1 ANGL. DEV. = 5.0 DEGREES
REMARK 500 ARG B 388 NE - CZ - NH2 ANGL. DEV. = -5.3 DEGREES
REMARK 500 ARG B 506 NE - CZ - NH1 ANGL. DEV. = 3.5 DEGREES
REMARK 500 ARG B 506 NE - CZ - NH2 ANGL. DEV. = -4.2 DEGREES
REMARK 500
REMARK 500 REMARK: NULL
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 MET A 302 125.62 -170.04
REMARK 500 ARG A 385 -10.06 87.50
REMARK 500 ASP A 386 33.61 -147.94
REMARK 500 LEU A 398 19.33 56.24
REMARK 500 TYR A 463 64.57 60.34
REMARK 500 PRO A 485 124.04 -39.02
REMARK 500 GLU A 489 -38.76 -38.60
REMARK 500 THR A 521 -61.86 -101.76
REMARK 500 VAL B 323 122.08 -36.55
REMARK 500 ARG B 385 -8.89 85.27
REMARK 500 ASP B 386 34.18 -148.47
REMARK 500 LEU B 398 19.91 55.64
REMARK 500 TYR B 463 64.24 62.06
REMARK 500 PRO B 485 125.18 -39.67
REMARK 500 THR B 521 -61.29 -104.01
REMARK 500
REMARK 500 REMARK: NULL
REMARK 525
REMARK 525 SOLVENT
REMARK 525
REMARK 525 THE SOLVENT MOLECULES HAVE CHAIN IDENTIFIERS THAT
REMARK 525 INDICATE THE POLYMER CHAIN WITH WHICH THEY ARE MOST
REMARK 525 CLOSELY ASSOCIATED. THE REMARK LISTS ALL THE SOLVENT
REMARK 525 MOLECULES WHICH ARE MORE THAN 5A AWAY FROM THE
REMARK 525 NEAREST POLYMER CHAIN (M = MODEL NUMBER;
REMARK 525 RES=RESIDUE NAME; C=CHAIN IDENTIFIER; SSEQ=SEQUENCE
REMARK 525 NUMBER; I=INSERTION CODE):
REMARK 525
REMARK 525 M RES CSSEQI
REMARK 525 HOH A2038 DISTANCE = 7.42 ANGSTROMS
REMARK 525 HOH B2033 DISTANCE = 6.45 ANGSTROMS
REMARK 800
REMARK 800 SITE
REMARK 800 SITE_IDENTIFIER: AC1
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: BINDING SITE FOR RESIDUE NG7 A 1534
REMARK 800
REMARK 800 SITE_IDENTIFIER: AC2
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: BINDING SITE FOR RESIDUE MES A 1535
REMARK 800
REMARK 800 SITE_IDENTIFIER: AC3
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: BINDING SITE FOR RESIDUE GOL A 1536
REMARK 800
REMARK 800 SITE_IDENTIFIER: AC4
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: BINDING SITE FOR RESIDUE NG7 B 1534
REMARK 800
REMARK 800 SITE_IDENTIFIER: AC5
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: BINDING SITE FOR RESIDUE MES B 1535
REMARK 900
REMARK 900 RELATED ENTRIES
REMARK 900 RELATED ID: 1PRM RELATED DB: PDB
REMARK 900 C-SRC (SH3 DOMAIN) COMPLEXED WITH THE PROLINE-RICH LIGAND PLR1
REMARK 900 (AFAPPLPRR) (NMR, MINIMIZED AVERAGE STRUCTURE)
REMARK 900 RELATED ID: 1PRL RELATED DB: PDB
REMARK 900 C-SRC (SH3 DOMAIN) COMPLEXED WITH THE PROLINE-RICH LIGAND PLR1
REMARK 900 (AFAPPLPRR) (NMR, 16 STRUCTURES)
REMARK 900 RELATED ID: 1RLQ RELATED DB: PDB
REMARK 900 C-SRC (SH3 DOMAIN) COMPLEXED WITH THE PROLINE-RICH LIGAND RLP2
REMARK 900 (RALPPLPRY) (NMR, MINIMIZED AVERAGE STRUCTURE)
REMARK 900 RELATED ID: 1F1W RELATED DB: PDB
REMARK 900 SRC SH2 THREF1TRP MUTANT COMPLEXED WITH THE PHOSPHOPEPTIDE PYVNV
REMARK 900 RELATED ID: 1P13 RELATED DB: PDB
REMARK 900 CRYSTAL STRUCTURE OF THE SRC SH2 DOMAIN COMPLEXED WITHPEPTIDE
REMARK 900 (SDPYANFK)
REMARK 900 RELATED ID: 1SRL RELATED DB: PDB
REMARK 900 RELATED ID: 2PTK RELATED DB: PDB
REMARK 900 CHICKEN SRC TYROSINE KINASE
REMARK 900 RELATED ID: 1SRM RELATED DB: PDB
REMARK 900 RELATED ID: 1F2F RELATED DB: PDB
REMARK 900 SRC SH2 THREF1TRP MUTANT
REMARK 900 RELATED ID: 1RLP RELATED DB: PDB
REMARK 900 C-SRC (SH3 DOMAIN) COMPLEXED WITH THE PROLINE-RICH LIGAND RLP2
REMARK 900 (RALPPLPRY) (NMR, 16 STRUCTURES)
REMARK 900 RELATED ID: 1NLP RELATED DB: PDB
REMARK 900 STRUCTURE OF SIGNAL TRANSDUCTION PROTEIN, NMR, MINIMIZEDAVERAGE
REMARK 900 STRUCTURE
REMARK 900 RELATED ID: 1NLO RELATED DB: PDB
REMARK 900 STRUCTURE OF SIGNAL TRANSDUCTION PROTEIN, NMR, MINIMIZEDAVERAGE
REMARK 900 STRUCTURE
DBREF 4AGW A 251 533 UNP P00523 SRC_CHICK 251 533
DBREF 4AGW B 251 533 UNP P00523 SRC_CHICK 251 533
SEQADV 4AGW GLY A 248 UNP P00523 EXPRESSION TAG
SEQADV 4AGW HIS A 249 UNP P00523 EXPRESSION TAG
SEQADV 4AGW MET A 250 UNP P00523 EXPRESSION TAG
SEQADV 4AGW GLY B 248 UNP P00523 EXPRESSION TAG
SEQADV 4AGW HIS B 249 UNP P00523 EXPRESSION TAG
SEQADV 4AGW MET B 250 UNP P00523 EXPRESSION TAG
SEQRES 1 A 286 GLY HIS MET GLN THR GLN GLY LEU ALA LYS ASP ALA TRP
SEQRES 2 A 286 GLU ILE PRO ARG GLU SER LEU ARG LEU GLU VAL LYS LEU
SEQRES 3 A 286 GLY GLN GLY CYS PHE GLY GLU VAL TRP MET GLY THR TRP
SEQRES 4 A 286 ASN GLY THR THR ARG VAL ALA ILE LYS THR LEU LYS PRO
SEQRES 5 A 286 GLY THR MET SER PRO GLU ALA PHE LEU GLN GLU ALA GLN
SEQRES 6 A 286 VAL MET LYS LYS LEU ARG HIS GLU LYS LEU VAL GLN LEU
SEQRES 7 A 286 TYR ALA VAL VAL SER GLU GLU PRO ILE TYR ILE VAL THR
SEQRES 8 A 286 GLU TYR MET SER LYS GLY SER LEU LEU ASP PHE LEU LYS
SEQRES 9 A 286 GLY GLU MET GLY LYS TYR LEU ARG LEU PRO GLN LEU VAL
SEQRES 10 A 286 ASP MET ALA ALA GLN ILE ALA SER GLY MET ALA TYR VAL
SEQRES 11 A 286 GLU ARG MET ASN TYR VAL HIS ARG ASP LEU ARG ALA ALA
SEQRES 12 A 286 ASN ILE LEU VAL GLY GLU ASN LEU VAL CYS LYS VAL ALA
SEQRES 13 A 286 ASP PHE GLY LEU ALA ARG LEU ILE GLU ASP ASN GLU TYR
SEQRES 14 A 286 THR ALA ARG GLN GLY ALA LYS PHE PRO ILE LYS TRP THR
SEQRES 15 A 286 ALA PRO GLU ALA ALA LEU TYR GLY ARG PHE THR ILE LYS
SEQRES 16 A 286 SER ASP VAL TRP SER PHE GLY ILE LEU LEU THR GLU LEU
SEQRES 17 A 286 THR THR LYS GLY ARG VAL PRO TYR PRO GLY MET VAL ASN
SEQRES 18 A 286 ARG GLU VAL LEU ASP GLN VAL GLU ARG GLY TYR ARG MET
SEQRES 19 A 286 PRO CYS PRO PRO GLU CYS PRO GLU SER LEU HIS ASP LEU
SEQRES 20 A 286 MET CYS GLN CYS TRP ARG LYS ASP PRO GLU GLU ARG PRO
SEQRES 21 A 286 THR PHE GLU TYR LEU GLN ALA PHE LEU GLU ASP TYR PHE
SEQRES 22 A 286 THR SER THR GLU PRO GLN TYR GLN PRO GLY GLU ASN LEU
SEQRES 1 B 286 GLY HIS MET GLN THR GLN GLY LEU ALA LYS ASP ALA TRP
SEQRES 2 B 286 GLU ILE PRO ARG GLU SER LEU ARG LEU GLU VAL LYS LEU
SEQRES 3 B 286 GLY GLN GLY CYS PHE GLY GLU VAL TRP MET GLY THR TRP
SEQRES 4 B 286 ASN GLY THR THR ARG VAL ALA ILE LYS THR LEU LYS PRO
SEQRES 5 B 286 GLY THR MET SER PRO GLU ALA PHE LEU GLN GLU ALA GLN
SEQRES 6 B 286 VAL MET LYS LYS LEU ARG HIS GLU LYS LEU VAL GLN LEU
SEQRES 7 B 286 TYR ALA VAL VAL SER GLU GLU PRO ILE TYR ILE VAL THR
SEQRES 8 B 286 GLU TYR MET SER LYS GLY SER LEU LEU ASP PHE LEU LYS
SEQRES 9 B 286 GLY GLU MET GLY LYS TYR LEU ARG LEU PRO GLN LEU VAL
SEQRES 10 B 286 ASP MET ALA ALA GLN ILE ALA SER GLY MET ALA TYR VAL
SEQRES 11 B 286 GLU ARG MET ASN TYR VAL HIS ARG ASP LEU ARG ALA ALA
SEQRES 12 B 286 ASN ILE LEU VAL GLY GLU ASN LEU VAL CYS LYS VAL ALA
SEQRES 13 B 286 ASP PHE GLY LEU ALA ARG LEU ILE GLU ASP ASN GLU TYR
SEQRES 14 B 286 THR ALA ARG GLN GLY ALA LYS PHE PRO ILE LYS TRP THR
SEQRES 15 B 286 ALA PRO GLU ALA ALA LEU TYR GLY ARG PHE THR ILE LYS
SEQRES 16 B 286 SER ASP VAL TRP SER PHE GLY ILE LEU LEU THR GLU LEU
SEQRES 17 B 286 THR THR LYS GLY ARG VAL PRO TYR PRO GLY MET VAL ASN
SEQRES 18 B 286 ARG GLU VAL LEU ASP GLN VAL GLU ARG GLY TYR ARG MET
SEQRES 19 B 286 PRO CYS PRO PRO GLU CYS PRO GLU SER LEU HIS ASP LEU
SEQRES 20 B 286 MET CYS GLN CYS TRP ARG LYS ASP PRO GLU GLU ARG PRO
SEQRES 21 B 286 THR PHE GLU TYR LEU GLN ALA PHE LEU GLU ASP TYR PHE
SEQRES 22 B 286 THR SER THR GLU PRO GLN TYR GLN PRO GLY GLU ASN LEU
HET NG7 A1534 43
HET MES A1535 12
HET GOL A1536 6
HET NG7 B1534 43
HET MES B1535 12
HETNAM NG7 3-{2-[(CYCLOPROPYLCARBONYL)AMINO][1,3]THIAZOLO[5,4-
HETNAM 2 NG7 B]PYRIDIN-5-YL}-N-{4-[(4-ETHYLPIPERAZIN-1-YL)METHYL]-
HETNAM 3 NG7 3-(TRIFLUOROMET HYL)PHENYL}BENZAMIDE
HETNAM MES 2-(N-MORPHOLINO)-ETHANESULFONIC ACID
HETNAM GOL GLYCEROL
HETSYN NG7 HG-7-85-01
HETSYN GOL GLYCERIN; PROPANE-1,2,3-TRIOL
FORMUL 3 NG7 2(C31 H31 F3 N6 O2 S)
FORMUL 4 MES 2(C6 H13 N O4 S)
FORMUL 5 GOL C3 H8 O3
FORMUL 8 HOH *152(H2 O)
HELIX 1 1 PRO A 263 GLU A 265 5 3
HELIX 2 2 SER A 303 LEU A 308 1 6
HELIX 3 3 LEU A 308 LYS A 316 1 9
HELIX 4 4 SER A 345 GLY A 352 1 8
HELIX 5 5 GLU A 353 LEU A 358 5 6
HELIX 6 6 ARG A 359 MET A 380 1 22
HELIX 7 7 ARG A 388 ALA A 390 5 3
HELIX 8 8 GLU A 396 LEU A 398 5 3
HELIX 9 9 ALA A 430 GLY A 437 1 8
HELIX 10 10 THR A 440 THR A 457 1 18
HELIX 11 11 VAL A 467 GLY A 478 1 12
HELIX 12 12 PRO A 488 TRP A 499 1 12
HELIX 13 13 THR A 508 ASP A 518 1 11
HELIX 14 14 ASP A 518 THR A 523 1 6
HELIX 15 15 PRO B 263 LEU B 267 5 5
HELIX 16 16 SER B 303 LEU B 317 1 15
HELIX 17 17 SER B 345 GLY B 352 1 8
HELIX 18 18 GLU B 353 LEU B 358 5 6
HELIX 19 19 ARG B 359 MET B 380 1 22
HELIX 20 20 ARG B 388 ALA B 390 5 3
HELIX 21 21 GLU B 396 LEU B 398 5 3
HELIX 22 22 ALA B 430 GLY B 437 1 8
HELIX 23 23 THR B 440 THR B 457 1 18
HELIX 24 24 VAL B 467 GLY B 478 1 12
HELIX 25 25 PRO B 488 TRP B 499 1 12
HELIX 26 26 THR B 508 ASP B 518 1 11
HELIX 27 27 ASP B 518 THR B 523 1 6
SHEET 1 AA 5 LEU A 267 GLN A 275 0
SHEET 2 AA 5 GLU A 280 TRP A 286 -1 O VAL A 281 N LEU A 273
SHEET 3 AA 5 THR A 290 LEU A 297 -1 O THR A 290 N TRP A 286
SHEET 4 AA 5 ILE A 334 GLU A 339 -1 O ILE A 334 N LEU A 297
SHEET 5 AA 5 LEU A 325 VAL A 329 -1 N TYR A 326 O VAL A 337
SHEET 1 AB 2 ILE A 392 VAL A 394 0
SHEET 2 AB 2 CYS A 400 VAL A 402 -1 O LYS A 401 N LEU A 393
SHEET 1 BA 5 ARG B 268 GLY B 276 0
SHEET 2 BA 5 GLY B 279 TRP B 286 -1 O GLY B 279 N GLY B 276
SHEET 3 BA 5 THR B 290 LEU B 297 -1 O THR B 290 N TRP B 286
SHEET 4 BA 5 ILE B 334 GLU B 339 -1 O ILE B 334 N LEU B 297
SHEET 5 BA 5 LEU B 325 VAL B 329 -1 N TYR B 326 O VAL B 337
SHEET 1 BB 2 ILE B 392 VAL B 394 0
SHEET 2 BB 2 CYS B 400 VAL B 402 -1 O LYS B 401 N LEU B 393
CISPEP 1 GLU A 332 PRO A 333 0 -4.65
CISPEP 2 GLU B 332 PRO B 333 0 -4.92
SITE 1 AC1 23 LEU A 273 ALA A 293 LYS A 295 VAL A 313
SITE 2 AC1 23 MET A 314 LEU A 317 LEU A 322 THR A 338
SITE 3 AC1 23 GLU A 339 TYR A 340 MET A 341 SER A 342
SITE 4 AC1 23 LYS A 343 GLY A 344 VAL A 383 HIS A 384
SITE 5 AC1 23 ARG A 385 LEU A 393 VAL A 402 ALA A 403
SITE 6 AC1 23 ASP A 404 MES A1535 HOH A2004
SITE 1 AC2 5 MET A 380 ASN A 381 TYR A 382 VAL A 383
SITE 2 AC2 5 NG7 A1534
SITE 1 AC3 8 LYS A 427 VAL A 461 TYR A 463 PRO A 464
SITE 2 AC3 8 GLY A 465 GLU B 517 ASP B 518 THR B 521
SITE 1 AC4 23 LEU B 273 ALA B 293 LYS B 295 GLU B 310
SITE 2 AC4 23 VAL B 313 MET B 314 LEU B 317 LEU B 322
SITE 3 AC4 23 THR B 338 GLU B 339 TYR B 340 MET B 341
SITE 4 AC4 23 SER B 342 GLY B 344 VAL B 383 HIS B 384
SITE 5 AC4 23 ARG B 385 LEU B 393 VAL B 402 ALA B 403
SITE 6 AC4 23 ASP B 404 PHE B 405 MES B1535
SITE 1 AC5 5 MET B 380 ASN B 381 TYR B 382 VAL B 383
SITE 2 AC5 5 NG7 B1534
CRYST1 40.738 61.393 71.814 79.57 89.10 90.14 P 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 0.024547 0.000060 -0.000403 0.00000
SCALE2 0.000000 0.016289 -0.002999 0.00000
SCALE3 0.000000 0.000000 0.014161 0.00000
(ATOM LINES ARE NOT SHOWN.)
END
