HEADER ISOMERASE/DNA 08-DEC-03 1RRJ
TITLE STRUCTURAL MECHANISMS OF CAMPTOTHECIN RESISTANCE BY
TITLE 2 MUTATIONS IN HUMAN TOPOISOMERASE I
COMPND MOL_ID: 1;
COMPND 2 MOLECULE: 5'-
COMPND 3 D(*AP*AP*AP*AP*AP*GP*AP*CP*TP*T*GP*GP*AP*AP*AP*AP*AP*TP*TP*
COMPND 4 TP*TP*T)-3';
COMPND 5 CHAIN: B;
COMPND 6 ENGINEERED: YES;
COMPND 7 MOL_ID: 2;
COMPND 8 MOLECULE: 5'-
COMPND 9 D(*AP*AP*AP*AP*AP*TP*TP*TP*TP*TP*CP*CP*AP*AP*GP*TP*CP*TP*TP
COMPND 10 *TP*TP*T)-3';
COMPND 11 CHAIN: C;
COMPND 12 ENGINEERED: YES;
COMPND 13 MOL_ID: 3;
COMPND 14 MOLECULE: DNA TOPOISOMERASE I;
COMPND 15 CHAIN: A;
COMPND 16 EC: 5.99.1.2;
COMPND 17 ENGINEERED: YES;
COMPND 18 MUTATION: YES
SOURCE MOL_ID: 1;
SOURCE 2 SYNTHETIC: YES;
SOURCE 3 MOL_ID: 2;
SOURCE 4 SYNTHETIC: YES;
SOURCE 5 MOL_ID: 3;
SOURCE 6 ORGANISM_SCIENTIFIC: HOMO SAPIENS;
SOURCE 7 ORGANISM_COMMON: HUMAN;
SOURCE 8 ORGANISM_TAXID: 9606;
SOURCE 9 GENE: TOP1;
SOURCE 10 EXPRESSION_SYSTEM: SPODOPTERA FRUGIPERDA;
SOURCE 11 EXPRESSION_SYSTEM_COMMON: FALL ARMYWORM;
SOURCE 12 EXPRESSION_SYSTEM_TAXID: 7108;
SOURCE 13 EXPRESSION_SYSTEM_CELL_LINE: SF9;
SOURCE 14 EXPRESSION_SYSTEM_VECTOR_TYPE: BACULOVIRUS;
SOURCE 15 EXPRESSION_SYSTEM_VECTOR: PFACTBAC1
KEYWDS HUMAN TOPOISOMERASE I, TOPOTECAN, CAMPTOTHECIN, X-RAY
KEYWDS 2 CRYSTALLOGRAPHY, ISOMERASE/DNA COMPLEX
EXPDTA X-RAY DIFFRACTION
AUTHOR J.E.CHRENCIK,B.L.STAKER,A.B.BURGIN,L.STEWART,M.R.REDINBO
REVDAT 2 24-FEB-09 1RRJ 1 VERSN
REVDAT 1 06-JUL-04 1RRJ 0
JRNL AUTH J.E.CHRENCIK,B.L.STAKER,A.B.BURGIN,P.POURQUIER,
JRNL AUTH 2 Y.POMMIER,L.STEWART,M.R.REDINBO
JRNL TITL MECHANISMS OF CAMPTOTHECIN RESISTANCE BY HUMAN
JRNL TITL 2 TOPOISOMERASE I MUTATIONS
JRNL REF J.MOL.BIOL. V. 339 773 2004
JRNL REFN ISSN 0022-2836
JRNL PMID 15165849
JRNL DOI 10.1016/J.JMB.2004.03.077
REMARK 1
REMARK 2
REMARK 2 RESOLUTION. 2.30 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) : 2.30
REMARK 3 RESOLUTION RANGE LOW (ANGSTROMS) : 43.69
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) (%) : NULL
REMARK 3 NUMBER OF REFLECTIONS : 56412
REMARK 3
REMARK 3 FIT TO DATA USED IN REFINEMENT.
REMARK 3 CROSS-VALIDATION METHOD : THROUGHOUT
REMARK 3 FREE R VALUE TEST SET SELECTION : RANDOM
REMARK 3 R VALUE (WORKING SET) : 0.246
REMARK 3 FREE R VALUE : 0.278
REMARK 3 FREE R VALUE TEST SET SIZE (%) : NULL
REMARK 3 FREE R VALUE TEST SET COUNT : 4348
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 : 4701
REMARK 3 NUCLEIC ACID ATOMS : 892
REMARK 3 HETEROGEN ATOMS : 63
REMARK 3 SOLVENT ATOMS : 436
REMARK 3
REMARK 3 B VALUES.
REMARK 3 FROM WILSON PLOT (A**2) : 22.30
REMARK 3 MEAN B VALUE (OVERALL, A**2) : NULL
REMARK 3 OVERALL ANISOTROPIC B VALUE.
REMARK 3 B11 (A**2) : -2.50000
REMARK 3 B22 (A**2) : -0.57000
REMARK 3 B33 (A**2) : 3.08000
REMARK 3 B12 (A**2) : 0.00000
REMARK 3 B13 (A**2) : 2.43000
REMARK 3 B23 (A**2) : 0.00000
REMARK 3
REMARK 3 ESTIMATED COORDINATE ERROR.
REMARK 3 ESD FROM LUZZATI PLOT (A) : 0.32
REMARK 3 ESD FROM SIGMAA (A) : 0.25
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) : 0.37
REMARK 3 ESD FROM C-V SIGMAA (A) : 0.31
REMARK 3
REMARK 3 RMS DEVIATIONS FROM IDEAL VALUES.
REMARK 3 BOND LENGTHS (A) : 0.044
REMARK 3 BOND ANGLES (DEGREES) : 2.20
REMARK 3 DIHEDRAL ANGLES (DEGREES) : 22.10
REMARK 3 IMPROPER ANGLES (DEGREES) : 1.63
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 1RRJ COMPLIES WITH FORMAT V. 3.15, 01-DEC-08
REMARK 100
REMARK 100 THIS ENTRY HAS BEEN PROCESSED BY RCSB ON 20-JAN-04.
REMARK 100 THE RCSB ID CODE IS RCSB020987.
REMARK 200
REMARK 200 EXPERIMENTAL DETAILS
REMARK 200 EXPERIMENT TYPE : X-RAY DIFFRACTION
REMARK 200 DATE OF DATA COLLECTION : 04-FEB-03
REMARK 200 TEMPERATURE (KELVIN) : 100
REMARK 200 PH : 6.5
REMARK 200 NUMBER OF CRYSTALS USED : 1
REMARK 200
REMARK 200 SYNCHROTRON (Y/N) : Y
REMARK 200 RADIATION SOURCE : NSLS
REMARK 200 BEAMLINE : X25
REMARK 200 X-RAY GENERATOR MODEL : NULL
REMARK 200 MONOCHROMATIC OR LAUE (M/L) : M
REMARK 200 WAVELENGTH OR RANGE (A) : 1.1
REMARK 200 MONOCHROMATOR : YALE MIRRORS
REMARK 200 OPTICS : MIRRORS
REMARK 200
REMARK 200 DETECTOR TYPE : CCD
REMARK 200 DETECTOR MANUFACTURER : MARRESEARCH
REMARK 200 INTENSITY-INTEGRATION SOFTWARE : HKL-2000
REMARK 200 DATA SCALING SOFTWARE : CCP4 (TRUNCATE)
REMARK 200
REMARK 200 NUMBER OF UNIQUE REFLECTIONS : 56412
REMARK 200 RESOLUTION RANGE HIGH (A) : 2.300
REMARK 200 RESOLUTION RANGE LOW (A) : 43.690
REMARK 200 REJECTION CRITERIA (SIGMA(I)) : 0.000
REMARK 200
REMARK 200 OVERALL.
REMARK 200 COMPLETENESS FOR RANGE (%) : 99.5
REMARK 200 DATA REDUNDANCY : NULL
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) : 2.30
REMARK 200 HIGHEST RESOLUTION SHELL, RANGE LOW (A) : 2.44
REMARK 200 COMPLETENESS FOR SHELL (%) : 99.0
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: MOLECULAR REPLACEMENT
REMARK 200 SOFTWARE USED: AMORE
REMARK 200 STARTING MODEL: 1K4T
REMARK 200
REMARK 200 REMARK: NULL
REMARK 280
REMARK 280 CRYSTAL
REMARK 280 SOLVENT CONTENT, VS (%): 59.85
REMARK 280 MATTHEWS COEFFICIENT, VM (ANGSTROMS**3/DA): 3.06
REMARK 280
REMARK 280 CRYSTALLIZATION CONDITIONS: PEG8000, 200MM LITHIUM SULFATE,
REMARK 280 100MM MES, PH 6.5, VAPOR DIFFUSION, HANGING DROP, TEMPERATURE
REMARK 280 289K
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 57.67700
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: TRIMERIC
REMARK 350 APPLY THE FOLLOWING TO CHAINS: B, C, 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 470
REMARK 470 MISSING ATOM
REMARK 470 THE FOLLOWING RESIDUES HAVE MISSING ATOMS(M=MODEL NUMBER;
REMARK 470 RES=RESIDUE NAME; C=CHAIN IDENTIFIER; SSEQ=SEQUENCE NUMBER;
REMARK 470 I=INSERTION CODE):
REMARK 470 M RES CSSEQI ATOMS
REMARK 470 DT B 10 O3'
REMARK 470 DG B 11 P OP1 OP2
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 O5' DG B 11 O HOH B 2319 1.79
REMARK 500
REMARK 500 REMARK: NULL
REMARK 500
REMARK 500 GEOMETRY AND STEREOCHEMISTRY
REMARK 500 SUBTOPIC: COVALENT BOND LENGTHS
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,2(A3,1X,A1,I4,A1,1X,A4,3X),1X,F6.3)
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 RES CSSEQI ATM2 DEVIATION
REMARK 500 PHE A 640 N PHE A 640 CA 0.709
REMARK 500 LEU A 724 N LEU A 724 CA 0.240
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 LEU A 335 CA - CB - CG ANGL. DEV. = 13.9 DEGREES
REMARK 500 PHE A 640 N - CA - C ANGL. DEV. = -33.8 DEGREES
REMARK 500 PHE A 640 C - N - CA ANGL. DEV. = -20.0 DEGREES
REMARK 500 LEU A 724 N - CA - CB ANGL. DEV. = 19.5 DEGREES
REMARK 500 LEU A 724 N - CA - C ANGL. DEV. = -17.6 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 ASP A 344 88.41 34.92
REMARK 500 ASP A 500 97.62 -64.67
REMARK 500 PHE A 565 77.80 -102.52
REMARK 500 PRO A 637 111.15 -35.91
REMARK 500 LYS A 638 94.65 -22.68
REMARK 500 THR A 639 -1.78 57.41
REMARK 500 MET A 675 73.54 63.38
REMARK 500 MET A 758 78.46 -103.20
REMARK 500 ALA A 759 118.18 176.59
REMARK 500
REMARK 500 REMARK: NULL
REMARK 500
REMARK 500 GEOMETRY AND STEREOCHEMISTRY
REMARK 500 SUBTOPIC: NON-CIS, NON-TRANS
REMARK 500
REMARK 500 THE FOLLOWING PEPTIDE BONDS DEVIATE SIGNIFICANTLY FROM BOTH
REMARK 500 CIS AND TRANS CONFORMATION. CIS BONDS, IF ANY, ARE LISTED
REMARK 500 ON CISPEP RECORDS. TRANS IS DEFINED AS 180 +/- 30 AND
REMARK 500 CIS IS DEFINED AS 0 +/- 30 DEGREES.
REMARK 500 MODEL OMEGA
REMARK 500 THR A 639 PHE A 640 -113.95
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 TTG B 991
REMARK 800 SITE_IDENTIFIER: AC2
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: BINDING SITE FOR RESIDUE TTC B 990
REMARK 900
REMARK 900 RELATED ENTRIES
REMARK 900 RELATED ID: 1K4T RELATED DB: PDB
REMARK 900 RELATED ID: 1RR8 RELATED DB: PDB
REMARK 900 PHE361SER
DBREF 1RRJ A 201 765 UNP P11387 TOP1_HUMAN 201 765
DBREF 1RRJ B 1 22 PDB 1RRJ 1RRJ 1 22
DBREF 1RRJ C 101 122 PDB 1RRJ 1RRJ 101 122
SEQADV 1RRJ SER A 722 UNP P11387 ASN 722 ENGINEERED
SEQADV 1RRJ PTR A 723 UNP P11387 TYR 723 MODIFIED RESIDUE
SEQRES 1 B 22 DA DA DA DA DA DG DA DC DT DT DG DG DA
SEQRES 2 B 22 DA DA DA DA DT DT DT DT DT
SEQRES 1 C 22 DA DA DA DA DA DT DT DT DT DT DC DC DA
SEQRES 2 C 22 DA DG DT DC DT DT DT DT DT
SEQRES 1 A 565 GLN LYS TRP LYS TRP TRP GLU GLU GLU ARG TYR PRO GLU
SEQRES 2 A 565 GLY ILE LYS TRP LYS PHE LEU GLU HIS LYS GLY PRO VAL
SEQRES 3 A 565 PHE ALA PRO PRO TYR GLU PRO LEU PRO GLU ASN VAL LYS
SEQRES 4 A 565 PHE TYR TYR ASP GLY LYS VAL MET LYS LEU SER PRO LYS
SEQRES 5 A 565 ALA GLU GLU VAL ALA THR PHE PHE ALA LYS MET LEU ASP
SEQRES 6 A 565 HIS GLU TYR THR THR LYS GLU ILE PHE ARG LYS ASN PHE
SEQRES 7 A 565 PHE LYS ASP TRP ARG LYS GLU MET THR ASN GLU GLU LYS
SEQRES 8 A 565 ASN ILE ILE THR ASN LEU SER LYS CYS ASP PHE THR GLN
SEQRES 9 A 565 MET SER GLN TYR PHE LYS ALA GLN THR GLU ALA ARG LYS
SEQRES 10 A 565 GLN MET SER LYS GLU GLU LYS LEU LYS ILE LYS GLU GLU
SEQRES 11 A 565 ASN GLU LYS LEU LEU LYS GLU TYR GLY PHE CYS ILE MET
SEQRES 12 A 565 ASP ASN HIS LYS GLU ARG ILE ALA ASN PHE LYS ILE GLU
SEQRES 13 A 565 PRO PRO GLY LEU PHE ARG GLY ARG GLY ASN HIS PRO LYS
SEQRES 14 A 565 MET GLY MET LEU LYS ARG ARG ILE MET PRO GLU ASP ILE
SEQRES 15 A 565 ILE ILE ASN CYS SER LYS ASP ALA LYS VAL PRO SER PRO
SEQRES 16 A 565 PRO PRO GLY HIS LYS TRP LYS GLU VAL ARG HIS ASP ASN
SEQRES 17 A 565 LYS VAL THR TRP LEU VAL SER TRP THR GLU ASN ILE GLN
SEQRES 18 A 565 GLY SER ILE LYS TYR ILE MET LEU ASN PRO SER SER ARG
SEQRES 19 A 565 ILE LYS GLY GLU LYS ASP TRP GLN LYS TYR GLU THR ALA
SEQRES 20 A 565 ARG ARG LEU LYS LYS CYS VAL ASP LYS ILE ARG ASN GLN
SEQRES 21 A 565 TYR ARG GLU ASP TRP LYS SER LYS GLU MET LYS VAL ARG
SEQRES 22 A 565 GLN ARG ALA VAL ALA LEU TYR PHE ILE ASP LYS LEU ALA
SEQRES 23 A 565 LEU ARG ALA GLY ASN GLU LYS GLU GLU GLY GLU THR ALA
SEQRES 24 A 565 ASP THR VAL GLY CYS CYS SER LEU ARG VAL GLU HIS ILE
SEQRES 25 A 565 ASN LEU HIS PRO GLU LEU ASP GLY GLN GLU TYR VAL VAL
SEQRES 26 A 565 GLU PHE ASP PHE LEU GLY LYS ASP SER ILE ARG TYR TYR
SEQRES 27 A 565 ASN LYS VAL PRO VAL GLU LYS ARG VAL PHE LYS ASN LEU
SEQRES 28 A 565 GLN LEU PHE MET GLU ASN LYS GLN PRO GLU ASP ASP LEU
SEQRES 29 A 565 PHE ASP ARG LEU ASN THR GLY ILE LEU ASN LYS HIS LEU
SEQRES 30 A 565 GLN ASP LEU MET GLU GLY LEU THR ALA LYS VAL PHE ARG
SEQRES 31 A 565 THR TYR ASN ALA SER ILE THR LEU GLN GLN GLN LEU LYS
SEQRES 32 A 565 GLU LEU THR ALA PRO ASP GLU ASN ILE PRO ALA LYS ILE
SEQRES 33 A 565 LEU SER TYR ASN ARG ALA ASN ARG ALA VAL ALA ILE LEU
SEQRES 34 A 565 CYS ASN HIS GLN ARG ALA PRO PRO LYS THR PHE GLU LYS
SEQRES 35 A 565 SER MET MET ASN LEU GLN THR LYS ILE ASP ALA LYS LYS
SEQRES 36 A 565 GLU GLN LEU ALA ASP ALA ARG ARG ASP LEU LYS SER ALA
SEQRES 37 A 565 LYS ALA ASP ALA LYS VAL MET LYS ASP ALA LYS THR LYS
SEQRES 38 A 565 LYS VAL VAL GLU SER LYS LYS LYS ALA VAL GLN ARG LEU
SEQRES 39 A 565 GLU GLU GLN LEU MET LYS LEU GLU VAL GLN ALA THR ASP
SEQRES 40 A 565 ARG GLU GLU ASN LYS GLN ILE ALA LEU GLY THR SER LYS
SEQRES 41 A 565 LEU SER PTR LEU ASP PRO ARG ILE THR VAL ALA TRP CYS
SEQRES 42 A 565 LYS LYS TRP GLY VAL PRO ILE GLU LYS ILE TYR ASN LYS
SEQRES 43 A 565 THR GLN ARG GLU LYS PHE ALA TRP ALA ILE ASP MET ALA
SEQRES 44 A 565 ASP GLU ASP TYR GLU PHE
MODRES 1RRJ PTR A 723 TYR O-PHOSPHOTYROSINE
HET PTR A 723 16
HET TTG B 991 32
HET TTC B 990 31
HETNAM PTR O-PHOSPHOTYROSINE
HETNAM TTG 2-(1-DIMETHYLAMINOMETHYL-2-HYDROXY-8-HYDROXYMETHYL-9-
HETNAM 2 TTG OXO-9,11-DIHYDRO-INDOLIZINO[1,2-B]QUINOLIN-7-YL)-2-
HETNAM 3 TTG HYDROXY-BUTYRIC ACID
HETNAM TTC (S)-10-[(DIMETHYLAMINO)METHYL]-4-ETHYL-4,9-DIHYDROXY-
HETNAM 2 TTC 1H-PYRANO[3',4':6,7]INOLIZINO[1,2-B]-QUINOLINE-3,
HETNAM 3 TTC 14(4H,12H)-DIONE
HETSYN PTR PHOSPHONOTYROSINE
HETSYN TTG HYDROLYZED PRODUCT OF TOPOTECAN
HETSYN TTC TOPOTECAN, HYCAMTIN
FORMUL 3 PTR C9 H12 N O6 P
FORMUL 4 TTG C23 H25 N3 O6
FORMUL 4 TTC C23 H23 N3 O5
FORMUL 5 HOH *436(H2 O)
HELIX 1 1 LYS A 204 GLU A 208 5 5
HELIX 2 2 SER A 250 LYS A 262 1 13
HELIX 3 3 HIS A 266 THR A 270 5 5
HELIX 4 4 LYS A 271 MET A 286 1 16
HELIX 5 5 THR A 287 ASN A 292 1 6
HELIX 6 6 PHE A 302 LYS A 317 1 16
HELIX 7 7 SER A 320 GLY A 339 1 20
HELIX 8 8 MET A 378 ASP A 381 5 4
HELIX 9 9 SER A 433 LYS A 452 1 20
HELIX 10 10 CYS A 453 ASP A 464 1 12
HELIX 11 11 TRP A 465 SER A 467 5 3
HELIX 12 12 GLU A 469 LEU A 485 1 17
HELIX 13 13 ARG A 508 GLU A 510 5 3
HELIX 14 14 LYS A 532 SER A 534 5 3
HELIX 15 15 GLU A 544 MET A 555 1 12
HELIX 16 16 ASN A 569 MET A 581 1 13
HELIX 17 17 ALA A 586 THR A 606 1 21
HELIX 18 18 ASN A 611 CYS A 630 1 20
HELIX 19 19 THR A 639 GLU A 641 5 3
HELIX 20 20 LYS A 642 ASP A 671 1 30
HELIX 21 21 THR A 680 ASN A 711 1 32
HELIX 22 22 LEU A 716 SER A 722 1 7
HELIX 23 23 ASP A 725 GLY A 737 1 13
HELIX 24 24 PRO A 739 ILE A 743 5 5
HELIX 25 25 ASN A 745 PHE A 752 1 8
HELIX 26 26 PHE A 752 MET A 758 1 7
SHEET 1 A 3 LEU A 220 GLU A 221 0
SHEET 2 A 3 PHE A 340 MET A 343 -1 O ILE A 342 N GLU A 221
SHEET 3 A 3 HIS A 346 ARG A 349 -1 O GLU A 348 N CYS A 341
SHEET 1 B 3 LYS A 245 VAL A 246 0
SHEET 2 B 3 TYR A 241 TYR A 242 -1 N TYR A 242 O LYS A 245
SHEET 3 B 3 CYS A 300 ASP A 301 -1 O ASP A 301 N TYR A 241
SHEET 1 C 2 GLY A 359 LEU A 360 0
SHEET 2 C 2 LEU A 373 LYS A 374 -1 O LYS A 374 N GLY A 359
SHEET 1 D 4 GLU A 403 ARG A 405 0
SHEET 2 D 4 ILE A 383 ASN A 385 1 N ILE A 384 O ARG A 405
SHEET 3 D 4 VAL A 414 THR A 417 -1 O SER A 415 N ILE A 383
SHEET 4 D 4 ILE A 424 ILE A 427 -1 O LYS A 425 N TRP A 416
SHEET 1 E 3 ILE A 512 LEU A 518 0
SHEET 2 E 3 GLN A 521 LEU A 530 -1 O GLU A 526 N ASN A 513
SHEET 3 E 3 ARG A 536 PRO A 542 -1 O TYR A 537 N PHE A 529
LINK C3' DT B 10 O3P PTR A 723 1555 1555 2.13
LINK C SER A 722 N PTR A 723 1555 1555 1.34
LINK C PTR A 723 N LEU A 724 1555 1555 1.42
SITE 1 AC1 15 GLU A 356 ARG A 364 LYS A 532 ASP A 533
SITE 2 AC1 15 THR A 718 DT B 10 DG B 11 TTC B 990
SITE 3 AC1 15 HOH B2001 HOH B2180 HOH B2217 HOH B2293
SITE 4 AC1 15 HOH B2319 DC C 112 DA C 113
SITE 1 AC2 15 GLU A 356 ARG A 364 LYS A 532 ASP A 533
SITE 2 AC2 15 THR A 718 PTR A 723 DT B 10 DG B 11
SITE 3 AC2 15 TTG B 991 HOH B2001 HOH B2180 HOH B2217
SITE 4 AC2 15 HOH B2293 DC C 112 DA C 113
CRYST1 57.333 115.354 75.172 90.00 94.33 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 0.017442 0.000000 0.001320 0.00000
SCALE2 0.000000 0.008669 0.000000 0.00000
SCALE3 0.000000 0.000000 0.013341 0.00000
(ATOM LINES ARE NOT SHOWN.)
END
