HEADER OXIDOREDUCTASE/OXIDOREDUCTASE INHIBITOR 11-DEC-13 4NZ2
TITLE CRYSTAL STRUCTURE OF CYP2C9 IN COMPLEX WITH AN INHIBITOR
COMPND MOL_ID: 1;
COMPND 2 MOLECULE: CYTOCHROME P450 2C9;
COMPND 3 CHAIN: A, B;
COMPND 4 FRAGMENT: UNP RESIDUES 30-490;
COMPND 5 SYNONYM: (R)-LIMONENE 6-MONOOXYGENASE, (S)-LIMONENE 6-MONOOXYGENASE,
COMPND 6 (S)-LIMONENE 7-MONOOXYGENASE, CYPIIC9, CYTOCHROME P-450MP, CYTOCHROME
COMPND 7 P450 MP-4, CYTOCHROME P450 MP-8, CYTOCHROME P450 PB-1, S-MEPHENYTOIN
COMPND 8 4-HYDROXYLASE;
COMPND 9 EC: 1.14.13.-, 1.14.13.80, 1.14.13.48, 1.14.13.49;
COMPND 10 ENGINEERED: YES;
COMPND 11 MUTATION: YES
SOURCE MOL_ID: 1;
SOURCE 2 ORGANISM_SCIENTIFIC: HOMO SAPIENS;
SOURCE 3 ORGANISM_COMMON: HUMAN;
SOURCE 4 ORGANISM_TAXID: 9606;
SOURCE 5 GENE: CYP2C10, CYP2C9, CYP2C9 CYP2C10;
SOURCE 6 EXPRESSION_SYSTEM: ESCHERICHIA COLI;
SOURCE 7 EXPRESSION_SYSTEM_TAXID: 562;
SOURCE 8 EXPRESSION_SYSTEM_STRAIN: XL1 BLUE
KEYWDS CYTOCHROME P-450, CYP2C9, INHIBITOR, STRUCTURE-BASED DRUG DESIGN,
KEYWDS 2 DRUG METABOLISM, MONOOXYGENASE, OXIDOREDUCTASE-OXIDOREDUCTASE
KEYWDS 3 INHIBITOR COMPLEX
EXPDTA X-RAY DIFFRACTION
AUTHOR G.BRANDEN,T.SJOGREN,Y.XUE
REVDAT 2 28-FEB-24 4NZ2 1 REMARK SEQADV LINK
REVDAT 1 13-AUG-14 4NZ2 0
JRNL AUTH G.BRANDEN,T.SJOGREN,V.SCHNECKE,Y.XUE
JRNL TITL STRUCTURE-BASED LIGAND DESIGN TO OVERCOME CYP INHIBITION IN
JRNL TITL 2 DRUG DISCOVERY PROJECTS.
JRNL REF DRUG DISCOV TODAY V. 19 905 2014
JRNL REFN ISSN 1359-6446
JRNL PMID 24642031
JRNL DOI 10.1016/J.DRUDIS.2014.03.012
REMARK 2
REMARK 2 RESOLUTION. 2.45 ANGSTROMS.
REMARK 3
REMARK 3 REFINEMENT.
REMARK 3 PROGRAM : BUSTER-TNT
REMARK 3 AUTHORS : BRICOGNE,BLANC,BRANDL,FLENSBURG,KELLER,
REMARK 3 : PACIOREK,ROVERSI,SMART,VONRHEIN,WOMACK,
REMARK 3 : MATTHEWS,TEN EYCK,TRONRUD
REMARK 3
REMARK 3 DATA USED IN REFINEMENT.
REMARK 3 RESOLUTION RANGE HIGH (ANGSTROMS) : 2.45
REMARK 3 RESOLUTION RANGE LOW (ANGSTROMS) : 48.47
REMARK 3 DATA CUTOFF (SIGMA(F)) : 0.000
REMARK 3 COMPLETENESS FOR RANGE (%) : 99.6
REMARK 3 NUMBER OF REFLECTIONS : 63852
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 + TEST SET) : 0.218
REMARK 3 R VALUE (WORKING SET) : 0.217
REMARK 3 FREE R VALUE : 0.235
REMARK 3 FREE R VALUE TEST SET SIZE (%) : 5.070
REMARK 3 FREE R VALUE TEST SET COUNT : 3238
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 : 20
REMARK 3 BIN RESOLUTION RANGE HIGH (ANGSTROMS) : 2.45
REMARK 3 BIN RESOLUTION RANGE LOW (ANGSTROMS) : 2.51
REMARK 3 BIN COMPLETENESS (WORKING+TEST) (%) : 99.62
REMARK 3 REFLECTIONS IN BIN (WORKING + TEST SET) : 4688
REMARK 3 BIN R VALUE (WORKING + TEST SET) : 0.3253
REMARK 3 REFLECTIONS IN BIN (WORKING SET) : 4446
REMARK 3 BIN R VALUE (WORKING SET) : 0.3241
REMARK 3 BIN FREE R VALUE : 0.3477
REMARK 3 BIN FREE R VALUE TEST SET SIZE (%) : 5.16
REMARK 3 BIN FREE R VALUE TEST SET COUNT : 242
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 : 7432
REMARK 3 NUCLEIC ACID ATOMS : 0
REMARK 3 HETEROGEN ATOMS : 162
REMARK 3 SOLVENT ATOMS : 328
REMARK 3
REMARK 3 B VALUES.
REMARK 3 FROM WILSON PLOT (A**2) : 57.41
REMARK 3 MEAN B VALUE (OVERALL, A**2) : 54.49
REMARK 3 OVERALL ANISOTROPIC B VALUE.
REMARK 3 B11 (A**2) : -3.79500
REMARK 3 B22 (A**2) : -3.79500
REMARK 3 B33 (A**2) : 7.59010
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) : 0.389
REMARK 3 DPI (BLOW EQ-10) BASED ON R VALUE (A) : NULL
REMARK 3 DPI (BLOW EQ-9) BASED ON FREE R VALUE (A) : NULL
REMARK 3 DPI (CRUICKSHANK) BASED ON R VALUE (A) : 0.263
REMARK 3 DPI (CRUICKSHANK) BASED ON FREE R VALUE (A) : NULL
REMARK 3
REMARK 3 REFERENCES: BLOW, D. (2002) ACTA CRYST D58, 792-797
REMARK 3 CRUICKSHANK, D.W.J. (1999) ACTA CRYST D55, 583-601
REMARK 3
REMARK 3 CORRELATION COEFFICIENTS.
REMARK 3 CORRELATION COEFFICIENT FO-FC : 0.930
REMARK 3 CORRELATION COEFFICIENT FO-FC FREE : 0.921
REMARK 3
REMARK 3 NUMBER OF GEOMETRIC FUNCTION TERMS DEFINED : 15
REMARK 3 TERM COUNT WEIGHT FUNCTION.
REMARK 3 BOND LENGTHS : 7788 ; 2.000 ; HARMONIC
REMARK 3 BOND ANGLES : 10574 ; 2.000 ; HARMONIC
REMARK 3 TORSION ANGLES : 2688 ; 2.000 ; SINUSOIDAL
REMARK 3 TRIGONAL CARBON PLANES : 184 ; 2.000 ; HARMONIC
REMARK 3 GENERAL PLANES : 1132 ; 5.000 ; HARMONIC
REMARK 3 ISOTROPIC THERMAL FACTORS : 7788 ; 20.000 ; HARMONIC
REMARK 3 BAD NON-BONDED CONTACTS : 2 ; 5.000 ; SEMIHARMONIC
REMARK 3 IMPROPER TORSIONS : NULL ; NULL ; NULL
REMARK 3 PSEUDOROTATION ANGLES : NULL ; NULL ; NULL
REMARK 3 CHIRAL IMPROPER TORSION : 986 ; 5.000 ; SEMIHARMONIC
REMARK 3 SUM OF OCCUPANCIES : NULL ; NULL ; NULL
REMARK 3 UTILITY DISTANCES : NULL ; NULL ; NULL
REMARK 3 UTILITY ANGLES : NULL ; NULL ; NULL
REMARK 3 UTILITY TORSION : NULL ; NULL ; NULL
REMARK 3 IDEAL-DIST CONTACT TERM : 9077 ; 4.000 ; SEMIHARMONIC
REMARK 3
REMARK 3 RMS DEVIATIONS FROM IDEAL VALUES.
REMARK 3 BOND LENGTHS (A) : 0.008
REMARK 3 BOND ANGLES (DEGREES) : 1.01
REMARK 3 PEPTIDE OMEGA TORSION ANGLES (DEGREES) : 2.06
REMARK 3 OTHER TORSION ANGLES (DEGREES) : 18.54
REMARK 3
REMARK 3 TLS DETAILS
REMARK 3 NUMBER OF TLS GROUPS : 2
REMARK 3
REMARK 3 TLS GROUP : 1
REMARK 3 SELECTION: { A|* }
REMARK 3 ORIGIN FOR THE GROUP (A): -55.4525 -48.9190 -20.8507
REMARK 3 T TENSOR
REMARK 3 T11: -0.1112 T22: 0.0428
REMARK 3 T33: -0.0865 T12: 0.0970
REMARK 3 T13: -0.0311 T23: -0.0328
REMARK 3 L TENSOR
REMARK 3 L11: 0.7740 L22: 0.7955
REMARK 3 L33: 1.3264 L12: -0.4012
REMARK 3 L13: -0.1516 L23: -0.1617
REMARK 3 S TENSOR
REMARK 3 S11: -0.0632 S12: -0.0382 S13: 0.0731
REMARK 3 S21: 0.0215 S22: 0.0464 S23: -0.0335
REMARK 3 S31: -0.0494 S32: -0.0243 S33: 0.0168
REMARK 3
REMARK 3 TLS GROUP : 2
REMARK 3 SELECTION: { B|* }
REMARK 3 ORIGIN FOR THE GROUP (A): -20.8793 -77.9792 -30.4723
REMARK 3 T TENSOR
REMARK 3 T11: -0.1384 T22: 0.0055
REMARK 3 T33: -0.0356 T12: 0.1231
REMARK 3 T13: 0.0041 T23: 0.0088
REMARK 3 L TENSOR
REMARK 3 L11: 0.2553 L22: 1.3145
REMARK 3 L33: 1.7932 L12: -0.1137
REMARK 3 L13: 0.0250 L23: 0.1659
REMARK 3 S TENSOR
REMARK 3 S11: -0.0393 S12: 0.0223 S13: 0.0123
REMARK 3 S21: 0.0322 S22: 0.0201 S23: 0.0234
REMARK 3 S31: 0.0329 S32: -0.0714 S33: 0.0192
REMARK 3
REMARK 3 OTHER REFINEMENT REMARKS: NULL
REMARK 4
REMARK 4 4NZ2 COMPLIES WITH FORMAT V. 3.30, 13-JUL-11
REMARK 100
REMARK 100 THIS ENTRY HAS BEEN PROCESSED BY RCSB ON 08-JAN-14.
REMARK 100 THE DEPOSITION ID IS D_1000083835.
REMARK 200
REMARK 200 EXPERIMENTAL DETAILS
REMARK 200 EXPERIMENT TYPE : X-RAY DIFFRACTION
REMARK 200 DATE OF DATA COLLECTION : 18-MAY-09
REMARK 200 TEMPERATURE (KELVIN) : 100
REMARK 200 PH : 8.0
REMARK 200 NUMBER OF CRYSTALS USED : 1
REMARK 200
REMARK 200 SYNCHROTRON (Y/N) : Y
REMARK 200 RADIATION SOURCE : ESRF
REMARK 200 BEAMLINE : ID23-1
REMARK 200 X-RAY GENERATOR MODEL : NULL
REMARK 200 MONOCHROMATIC OR LAUE (M/L) : M
REMARK 200 WAVELENGTH OR RANGE (A) : 1.0723
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 : MOSFLM
REMARK 200 DATA SCALING SOFTWARE : SCALA 3.2.21
REMARK 200
REMARK 200 NUMBER OF UNIQUE REFLECTIONS : 63852
REMARK 200 RESOLUTION RANGE HIGH (A) : 2.450
REMARK 200 RESOLUTION RANGE LOW (A) : 48.467
REMARK 200 REJECTION CRITERIA (SIGMA(I)) : NULL
REMARK 200
REMARK 200 OVERALL.
REMARK 200 COMPLETENESS FOR RANGE (%) : 99.8
REMARK 200 DATA REDUNDANCY : 4.000
REMARK 200 R MERGE (I) : 0.06700
REMARK 200 R SYM (I) : NULL
REMARK 200 <I/SIGMA(I)> FOR THE DATA SET : 13.5000
REMARK 200
REMARK 200 IN THE HIGHEST RESOLUTION SHELL.
REMARK 200 HIGHEST RESOLUTION SHELL, RANGE HIGH (A) : 2.45
REMARK 200 HIGHEST RESOLUTION SHELL, RANGE LOW (A) : 2.51
REMARK 200 COMPLETENESS FOR SHELL (%) : 99.7
REMARK 200 DATA REDUNDANCY IN SHELL : 4.00
REMARK 200 R MERGE FOR SHELL (I) : 0.52600
REMARK 200 R SYM FOR SHELL (I) : NULL
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: PHASER
REMARK 200 STARTING MODEL: NULL
REMARK 200
REMARK 200 REMARK: NULL
REMARK 280
REMARK 280 CRYSTAL
REMARK 280 SOLVENT CONTENT, VS (%): 69.38
REMARK 280 MATTHEWS COEFFICIENT, VM (ANGSTROMS**3/DA): 4.02
REMARK 280
REMARK 280 CRYSTALLIZATION CONDITIONS: PEG 4000, LISO4, TRIS-HCL, DTT,
REMARK 280 GLYCEROL, PH 8.0, VAPOR DIFFUSION, TEMPERATURE 293K
REMARK 290
REMARK 290 CRYSTALLOGRAPHIC SYMMETRY
REMARK 290 SYMMETRY OPERATORS FOR SPACE GROUP: P 3 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
REMARK 290 3555 -X+Y,-X,Z
REMARK 290 4555 Y,X,-Z
REMARK 290 5555 X-Y,-Y,-Z
REMARK 290 6555 -X,-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 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 0.00000
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 0.00000
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 0.00000
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 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 MET A 20
REMARK 465 ALA A 21
REMARK 465 LYS A 22
REMARK 465 LYS A 23
REMARK 465 THR A 24
REMARK 465 SER A 25
REMARK 465 SER A 26
REMARK 465 HIS A 491
REMARK 465 HIS A 492
REMARK 465 HIS A 493
REMARK 465 HIS A 494
REMARK 465 MET B 20
REMARK 465 ALA B 21
REMARK 465 LYS B 22
REMARK 465 LYS B 23
REMARK 465 THR B 24
REMARK 465 SER B 25
REMARK 465 SER B 26
REMARK 465 HIS B 491
REMARK 465 HIS B 492
REMARK 465 HIS B 493
REMARK 465 HIS B 494
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 VAL A 38 -53.89 61.56
REMARK 500 ILE A 47 -40.59 -148.18
REMARK 500 LYS A 48 -75.40 -69.20
REMARK 500 HIS A 184 -9.51 59.48
REMARK 500 TYR A 189 2.23 -62.18
REMARK 500 ASN A 258 -14.23 87.07
REMARK 500 ASN A 277 62.13 73.31
REMARK 500 SER A 280 130.89 43.25
REMARK 500 THR A 299 -70.32 -94.45
REMARK 500 SER A 365 -137.76 52.10
REMARK 500 ASN A 403 67.27 65.85
REMARK 500 SER A 429 -159.29 70.09
REMARK 500 ASP A 463 141.14 88.62
REMARK 500 PRO B 37 -63.30 -22.08
REMARK 500 ILE B 47 -16.34 -142.02
REMARK 500 LYS B 48 -110.68 -81.39
REMARK 500 ILE B 88 -60.88 -103.77
REMARK 500 MET B 136 58.99 -141.81
REMARK 500 HIS B 184 123.91 76.73
REMARK 500 LYS B 185 137.67 76.89
REMARK 500 GLU B 274 10.02 58.23
REMARK 500 THR B 299 -71.43 -92.61
REMARK 500 SER B 365 -136.98 49.79
REMARK 500 ASN B 378 -1.13 75.09
REMARK 500 ASN B 403 66.97 63.22
REMARK 500 SER B 429 -159.70 71.62
REMARK 500 ASP B 463 148.52 97.32
REMARK 500
REMARK 500 REMARK: NULL
REMARK 620
REMARK 620 METAL COORDINATION
REMARK 620 (M=MODEL NUMBER; RES=RESIDUE NAME; C=CHAIN IDENTIFIER;
REMARK 620 SSEQ=SEQUENCE NUMBER; I=INSERTION CODE):
REMARK 620
REMARK 620 COORDINATION ANGLES FOR: M RES CSSEQI METAL
REMARK 620 HEM A 501 FE
REMARK 620 N RES CSSEQI ATOM
REMARK 620 1 CYS A 435 SG
REMARK 620 2 HEM A 501 NA 100.5
REMARK 620 3 HEM A 501 NB 89.6 89.2
REMARK 620 4 HEM A 501 NC 86.3 173.3 90.4
REMARK 620 5 HEM A 501 ND 99.3 89.6 171.1 89.7
REMARK 620 6 HOH A 647 O 170.9 79.4 81.3 93.9 89.8
REMARK 620 N 1 2 3 4 5
REMARK 620
REMARK 620 COORDINATION ANGLES FOR: M RES CSSEQI METAL
REMARK 620 HEM B 501 FE
REMARK 620 N RES CSSEQI ATOM
REMARK 620 1 CYS B 435 SG
REMARK 620 2 HEM B 501 NA 101.5
REMARK 620 3 HEM B 501 NB 89.8 89.5
REMARK 620 4 HEM B 501 NC 86.6 171.9 89.8
REMARK 620 5 HEM B 501 ND 100.7 89.9 169.4 89.3
REMARK 620 6 HOH B 755 O 169.2 83.0 80.3 88.9 89.1
REMARK 620 N 1 2 3 4 5
REMARK 800
REMARK 800 SITE
REMARK 800 SITE_IDENTIFIER: AC1
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: BINDING SITE FOR RESIDUE HEM A 501
REMARK 800
REMARK 800 SITE_IDENTIFIER: AC2
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: BINDING SITE FOR RESIDUE GOL A 502
REMARK 800
REMARK 800 SITE_IDENTIFIER: AC3
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: BINDING SITE FOR RESIDUE SO4 A 503
REMARK 800
REMARK 800 SITE_IDENTIFIER: AC4
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: BINDING SITE FOR RESIDUE 2QJ A 504
REMARK 800
REMARK 800 SITE_IDENTIFIER: AC5
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: BINDING SITE FOR RESIDUE HEM B 501
REMARK 800
REMARK 800 SITE_IDENTIFIER: AC6
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: BINDING SITE FOR RESIDUE GOL B 502
REMARK 800
REMARK 800 SITE_IDENTIFIER: AC7
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: BINDING SITE FOR RESIDUE SO4 B 503
REMARK 800
REMARK 800 SITE_IDENTIFIER: AC8
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: BINDING SITE FOR RESIDUE 2QJ B 504
REMARK 900
REMARK 900 RELATED ENTRIES
REMARK 900 RELATED ID: 4NY4 RELATED DB: PDB
DBREF 4NZ2 A 30 490 UNP P11712 CP2C9_HUMAN 30 490
DBREF 4NZ2 B 30 490 UNP P11712 CP2C9_HUMAN 30 490
SEQADV 4NZ2 MET A 20 UNP P11712 INSERTION
SEQADV 4NZ2 ALA A 21 UNP P11712 INSERTION
SEQADV 4NZ2 LYS A 22 UNP P11712 INSERTION
SEQADV 4NZ2 LYS A 23 UNP P11712 INSERTION
SEQADV 4NZ2 THR A 24 UNP P11712 INSERTION
SEQADV 4NZ2 SER A 25 UNP P11712 INSERTION
SEQADV 4NZ2 SER A 26 UNP P11712 INSERTION
SEQADV 4NZ2 LYS A 27 UNP P11712 INSERTION
SEQADV 4NZ2 GLY A 28 UNP P11712 INSERTION
SEQADV 4NZ2 ARG A 29 UNP P11712 INSERTION
SEQADV 4NZ2 GLU A 206 UNP P11712 LYS 206 ENGINEERED MUTATION
SEQADV 4NZ2 VAL A 215 UNP P11712 ILE 215 ENGINEERED MUTATION
SEQADV 4NZ2 TYR A 216 UNP P11712 CYS 216 ENGINEERED MUTATION
SEQADV 4NZ2 PRO A 220 UNP P11712 SER 220 ENGINEERED MUTATION
SEQADV 4NZ2 ALA A 221 UNP P11712 PRO 221 ENGINEERED MUTATION
SEQADV 4NZ2 LEU A 222 UNP P11712 ILE 222 ENGINEERED MUTATION
SEQADV 4NZ2 LEU A 223 UNP P11712 ILE 223 ENGINEERED MUTATION
SEQADV 4NZ2 HIS A 491 UNP P11712 EXPRESSION TAG
SEQADV 4NZ2 HIS A 492 UNP P11712 EXPRESSION TAG
SEQADV 4NZ2 HIS A 493 UNP P11712 EXPRESSION TAG
SEQADV 4NZ2 HIS A 494 UNP P11712 EXPRESSION TAG
SEQADV 4NZ2 MET B 20 UNP P11712 INSERTION
SEQADV 4NZ2 ALA B 21 UNP P11712 INSERTION
SEQADV 4NZ2 LYS B 22 UNP P11712 INSERTION
SEQADV 4NZ2 LYS B 23 UNP P11712 INSERTION
SEQADV 4NZ2 THR B 24 UNP P11712 INSERTION
SEQADV 4NZ2 SER B 25 UNP P11712 INSERTION
SEQADV 4NZ2 SER B 26 UNP P11712 INSERTION
SEQADV 4NZ2 LYS B 27 UNP P11712 INSERTION
SEQADV 4NZ2 GLY B 28 UNP P11712 INSERTION
SEQADV 4NZ2 ARG B 29 UNP P11712 INSERTION
SEQADV 4NZ2 GLU B 206 UNP P11712 LYS 206 ENGINEERED MUTATION
SEQADV 4NZ2 VAL B 215 UNP P11712 ILE 215 ENGINEERED MUTATION
SEQADV 4NZ2 TYR B 216 UNP P11712 CYS 216 ENGINEERED MUTATION
SEQADV 4NZ2 PRO B 220 UNP P11712 SER 220 ENGINEERED MUTATION
SEQADV 4NZ2 ALA B 221 UNP P11712 PRO 221 ENGINEERED MUTATION
SEQADV 4NZ2 LEU B 222 UNP P11712 ILE 222 ENGINEERED MUTATION
SEQADV 4NZ2 LEU B 223 UNP P11712 ILE 223 ENGINEERED MUTATION
SEQADV 4NZ2 HIS B 491 UNP P11712 EXPRESSION TAG
SEQADV 4NZ2 HIS B 492 UNP P11712 EXPRESSION TAG
SEQADV 4NZ2 HIS B 493 UNP P11712 EXPRESSION TAG
SEQADV 4NZ2 HIS B 494 UNP P11712 EXPRESSION TAG
SEQRES 1 A 475 MET ALA LYS LYS THR SER SER LYS GLY ARG PRO PRO GLY
SEQRES 2 A 475 PRO THR PRO LEU PRO VAL ILE GLY ASN ILE LEU GLN ILE
SEQRES 3 A 475 GLY ILE LYS ASP ILE SER LYS SER LEU THR ASN LEU SER
SEQRES 4 A 475 LYS VAL TYR GLY PRO VAL PHE THR LEU TYR PHE GLY LEU
SEQRES 5 A 475 LYS PRO ILE VAL VAL LEU HIS GLY TYR GLU ALA VAL LYS
SEQRES 6 A 475 GLU ALA LEU ILE ASP LEU GLY GLU GLU PHE SER GLY ARG
SEQRES 7 A 475 GLY ILE PHE PRO LEU ALA GLU ARG ALA ASN ARG GLY PHE
SEQRES 8 A 475 GLY ILE VAL PHE SER ASN GLY LYS LYS TRP LYS GLU ILE
SEQRES 9 A 475 ARG ARG PHE SER LEU MET THR LEU ARG ASN PHE GLY MET
SEQRES 10 A 475 GLY LYS ARG SER ILE GLU ASP ARG VAL GLN GLU GLU ALA
SEQRES 11 A 475 ARG CYS LEU VAL GLU GLU LEU ARG LYS THR LYS ALA SER
SEQRES 12 A 475 PRO CYS ASP PRO THR PHE ILE LEU GLY CYS ALA PRO CYS
SEQRES 13 A 475 ASN VAL ILE CYS SER ILE ILE PHE HIS LYS ARG PHE ASP
SEQRES 14 A 475 TYR LYS ASP GLN GLN PHE LEU ASN LEU MET GLU LYS LEU
SEQRES 15 A 475 ASN GLU ASN ILE GLU ILE LEU SER SER PRO TRP ILE GLN
SEQRES 16 A 475 VAL TYR ASN ASN PHE PRO ALA LEU LEU ASP TYR PHE PRO
SEQRES 17 A 475 GLY THR HIS ASN LYS LEU LEU LYS ASN VAL ALA PHE MET
SEQRES 18 A 475 LYS SER TYR ILE LEU GLU LYS VAL LYS GLU HIS GLN GLU
SEQRES 19 A 475 SER MET ASP MET ASN ASN PRO GLN ASP PHE ILE ASP CYS
SEQRES 20 A 475 PHE LEU MET LYS MET GLU LYS GLU LYS HIS ASN GLN PRO
SEQRES 21 A 475 SER GLU PHE THR ILE GLU SER LEU GLU ASN THR ALA VAL
SEQRES 22 A 475 ASP LEU PHE GLY ALA GLY THR GLU THR THR SER THR THR
SEQRES 23 A 475 LEU ARG TYR ALA LEU LEU LEU LEU LEU LYS HIS PRO GLU
SEQRES 24 A 475 VAL THR ALA LYS VAL GLN GLU GLU ILE GLU ARG VAL ILE
SEQRES 25 A 475 GLY ARG ASN ARG SER PRO CYS MET GLN ASP ARG SER HIS
SEQRES 26 A 475 MET PRO TYR THR ASP ALA VAL VAL HIS GLU VAL GLN ARG
SEQRES 27 A 475 TYR ILE ASP LEU LEU PRO THR SER LEU PRO HIS ALA VAL
SEQRES 28 A 475 THR CYS ASP ILE LYS PHE ARG ASN TYR LEU ILE PRO LYS
SEQRES 29 A 475 GLY THR THR ILE LEU ILE SER LEU THR SER VAL LEU HIS
SEQRES 30 A 475 ASP ASN LYS GLU PHE PRO ASN PRO GLU MET PHE ASP PRO
SEQRES 31 A 475 HIS HIS PHE LEU ASP GLU GLY GLY ASN PHE LYS LYS SER
SEQRES 32 A 475 LYS TYR PHE MET PRO PHE SER ALA GLY LYS ARG ILE CYS
SEQRES 33 A 475 VAL GLY GLU ALA LEU ALA GLY MET GLU LEU PHE LEU PHE
SEQRES 34 A 475 LEU THR SER ILE LEU GLN ASN PHE ASN LEU LYS SER LEU
SEQRES 35 A 475 VAL ASP PRO LYS ASN LEU ASP THR THR PRO VAL VAL ASN
SEQRES 36 A 475 GLY PHE ALA SER VAL PRO PRO PHE TYR GLN LEU CYS PHE
SEQRES 37 A 475 ILE PRO VAL HIS HIS HIS HIS
SEQRES 1 B 475 MET ALA LYS LYS THR SER SER LYS GLY ARG PRO PRO GLY
SEQRES 2 B 475 PRO THR PRO LEU PRO VAL ILE GLY ASN ILE LEU GLN ILE
SEQRES 3 B 475 GLY ILE LYS ASP ILE SER LYS SER LEU THR ASN LEU SER
SEQRES 4 B 475 LYS VAL TYR GLY PRO VAL PHE THR LEU TYR PHE GLY LEU
SEQRES 5 B 475 LYS PRO ILE VAL VAL LEU HIS GLY TYR GLU ALA VAL LYS
SEQRES 6 B 475 GLU ALA LEU ILE ASP LEU GLY GLU GLU PHE SER GLY ARG
SEQRES 7 B 475 GLY ILE PHE PRO LEU ALA GLU ARG ALA ASN ARG GLY PHE
SEQRES 8 B 475 GLY ILE VAL PHE SER ASN GLY LYS LYS TRP LYS GLU ILE
SEQRES 9 B 475 ARG ARG PHE SER LEU MET THR LEU ARG ASN PHE GLY MET
SEQRES 10 B 475 GLY LYS ARG SER ILE GLU ASP ARG VAL GLN GLU GLU ALA
SEQRES 11 B 475 ARG CYS LEU VAL GLU GLU LEU ARG LYS THR LYS ALA SER
SEQRES 12 B 475 PRO CYS ASP PRO THR PHE ILE LEU GLY CYS ALA PRO CYS
SEQRES 13 B 475 ASN VAL ILE CYS SER ILE ILE PHE HIS LYS ARG PHE ASP
SEQRES 14 B 475 TYR LYS ASP GLN GLN PHE LEU ASN LEU MET GLU LYS LEU
SEQRES 15 B 475 ASN GLU ASN ILE GLU ILE LEU SER SER PRO TRP ILE GLN
SEQRES 16 B 475 VAL TYR ASN ASN PHE PRO ALA LEU LEU ASP TYR PHE PRO
SEQRES 17 B 475 GLY THR HIS ASN LYS LEU LEU LYS ASN VAL ALA PHE MET
SEQRES 18 B 475 LYS SER TYR ILE LEU GLU LYS VAL LYS GLU HIS GLN GLU
SEQRES 19 B 475 SER MET ASP MET ASN ASN PRO GLN ASP PHE ILE ASP CYS
SEQRES 20 B 475 PHE LEU MET LYS MET GLU LYS GLU LYS HIS ASN GLN PRO
SEQRES 21 B 475 SER GLU PHE THR ILE GLU SER LEU GLU ASN THR ALA VAL
SEQRES 22 B 475 ASP LEU PHE GLY ALA GLY THR GLU THR THR SER THR THR
SEQRES 23 B 475 LEU ARG TYR ALA LEU LEU LEU LEU LEU LYS HIS PRO GLU
SEQRES 24 B 475 VAL THR ALA LYS VAL GLN GLU GLU ILE GLU ARG VAL ILE
SEQRES 25 B 475 GLY ARG ASN ARG SER PRO CYS MET GLN ASP ARG SER HIS
SEQRES 26 B 475 MET PRO TYR THR ASP ALA VAL VAL HIS GLU VAL GLN ARG
SEQRES 27 B 475 TYR ILE ASP LEU LEU PRO THR SER LEU PRO HIS ALA VAL
SEQRES 28 B 475 THR CYS ASP ILE LYS PHE ARG ASN TYR LEU ILE PRO LYS
SEQRES 29 B 475 GLY THR THR ILE LEU ILE SER LEU THR SER VAL LEU HIS
SEQRES 30 B 475 ASP ASN LYS GLU PHE PRO ASN PRO GLU MET PHE ASP PRO
SEQRES 31 B 475 HIS HIS PHE LEU ASP GLU GLY GLY ASN PHE LYS LYS SER
SEQRES 32 B 475 LYS TYR PHE MET PRO PHE SER ALA GLY LYS ARG ILE CYS
SEQRES 33 B 475 VAL GLY GLU ALA LEU ALA GLY MET GLU LEU PHE LEU PHE
SEQRES 34 B 475 LEU THR SER ILE LEU GLN ASN PHE ASN LEU LYS SER LEU
SEQRES 35 B 475 VAL ASP PRO LYS ASN LEU ASP THR THR PRO VAL VAL ASN
SEQRES 36 B 475 GLY PHE ALA SER VAL PRO PRO PHE TYR GLN LEU CYS PHE
SEQRES 37 B 475 ILE PRO VAL HIS HIS HIS HIS
HET HEM A 501 43
HET GOL A 502 6
HET SO4 A 503 5
HET 2QJ A 504 27
HET HEM B 501 43
HET GOL B 502 6
HET SO4 B 503 5
HET 2QJ B 504 27
HETNAM HEM PROTOPORPHYRIN IX CONTAINING FE
HETNAM GOL GLYCEROL
HETNAM SO4 SULFATE ION
HETNAM 2QJ (2R)-N-{4-[(3-BROMOPHENYL)SULFONYL]-2-CHLOROPHENYL}-3,
HETNAM 2 2QJ 3,3-TRIFLUORO-2-HYDROXY-2-METHYLPROPANAMIDE
HETSYN HEM HEME
HETSYN GOL GLYCERIN; PROPANE-1,2,3-TRIOL
FORMUL 3 HEM 2(C34 H32 FE N4 O4)
FORMUL 4 GOL 2(C3 H8 O3)
FORMUL 5 SO4 2(O4 S 2-)
FORMUL 6 2QJ 2(C16 H12 BR CL F3 N O4 S)
FORMUL 11 HOH *328(H2 O)
HELIX 1 1 ASN A 41 GLY A 46 1 6
HELIX 2 2 ASP A 49 GLY A 62 1 14
HELIX 3 3 GLY A 79 ILE A 88 1 10
HELIX 4 4 PHE A 100 ASN A 107 1 8
HELIX 5 5 ASN A 116 LEU A 131 1 16
HELIX 6 6 SER A 140 LYS A 158 1 19
HELIX 7 7 PRO A 166 PHE A 183 1 18
HELIX 8 8 ASP A 191 SER A 209 1 19
HELIX 9 9 SER A 210 TRP A 212 5 3
HELIX 10 10 ILE A 213 PHE A 219 1 7
HELIX 11 11 ALA A 221 PHE A 226 1 6
HELIX 12 12 PRO A 227 MET A 255 1 29
HELIX 13 13 ASP A 262 GLU A 274 1 13
HELIX 14 14 THR A 283 HIS A 316 1 34
HELIX 15 15 HIS A 316 ILE A 331 1 16
HELIX 16 16 CYS A 338 HIS A 344 5 7
HELIX 17 17 MET A 345 ASP A 360 1 16
HELIX 18 18 LEU A 391 HIS A 396 1 6
HELIX 19 19 ASP A 408 LEU A 413 5 6
HELIX 20 20 ALA A 430 ILE A 434 5 5
HELIX 21 21 GLY A 437 ASN A 455 1 19
HELIX 22 22 ASN B 41 GLY B 46 1 6
HELIX 23 23 ASP B 49 GLY B 62 1 14
HELIX 24 24 GLY B 79 ILE B 88 1 10
HELIX 25 25 PHE B 100 ASN B 107 1 8
HELIX 26 26 GLY B 117 LEU B 131 1 15
HELIX 27 27 SER B 140 LYS B 158 1 19
HELIX 28 28 PHE B 168 PHE B 183 1 16
HELIX 29 29 ASP B 191 SER B 209 1 19
HELIX 30 30 SER B 210 TRP B 212 5 3
HELIX 31 31 ILE B 213 PHE B 219 1 7
HELIX 32 32 ALA B 221 PHE B 226 1 6
HELIX 33 33 PRO B 227 MET B 255 1 29
HELIX 34 34 ASP B 262 LYS B 273 1 12
HELIX 35 35 THR B 283 THR B 299 1 17
HELIX 36 36 THR B 299 HIS B 316 1 18
HELIX 37 37 HIS B 316 ILE B 331 1 16
HELIX 38 38 CYS B 338 HIS B 344 5 7
HELIX 39 39 MET B 345 ASP B 360 1 16
HELIX 40 40 SER B 390 HIS B 396 1 7
HELIX 41 41 ASP B 408 LEU B 413 5 6
HELIX 42 42 GLY B 437 ASN B 455 1 19
SHEET 1 A 5 VAL A 64 PHE A 69 0
SHEET 2 A 5 LYS A 72 LEU A 77 -1 O VAL A 76 N PHE A 65
SHEET 3 A 5 THR A 386 ILE A 389 1 O LEU A 388 N LEU A 77
SHEET 4 A 5 HIS A 368 ALA A 369 -1 N HIS A 368 O ILE A 387
SHEET 5 A 5 GLY A 96 ARG A 97 -1 N GLY A 96 O ALA A 369
SHEET 1 B 2 ILE A 374 PHE A 376 0
SHEET 2 B 2 TYR A 379 ILE A 381 -1 O TYR A 379 N PHE A 376
SHEET 1 C 2 PHE A 456 SER A 460 0
SHEET 2 C 2 LEU A 485 PRO A 489 -1 O CYS A 486 N LYS A 459
SHEET 1 D 2 VAL A 472 VAL A 473 0
SHEET 2 D 2 SER A 478 VAL A 479 -1 O VAL A 479 N VAL A 472
SHEET 1 E 5 VAL B 64 PHE B 69 0
SHEET 2 E 5 LYS B 72 LEU B 77 -1 O VAL B 76 N PHE B 65
SHEET 3 E 5 THR B 386 ILE B 389 1 O LEU B 388 N LEU B 77
SHEET 4 E 5 HIS B 368 ALA B 369 -1 N HIS B 368 O ILE B 387
SHEET 5 E 5 GLY B 96 ARG B 97 -1 N GLY B 96 O ALA B 369
SHEET 1 F 2 ILE B 374 PHE B 376 0
SHEET 2 F 2 TYR B 379 ILE B 381 -1 O ILE B 381 N ILE B 374
SHEET 1 G 2 PHE B 456 SER B 460 0
SHEET 2 G 2 LEU B 485 PRO B 489 -1 O ILE B 488 N ASN B 457
SHEET 1 H 2 VAL B 472 VAL B 473 0
SHEET 2 H 2 SER B 478 VAL B 479 -1 O VAL B 479 N VAL B 472
LINK SG CYS A 435 FE HEM A 501 1555 1555 2.28
LINK FE HEM A 501 O HOH A 647 1555 1555 2.34
LINK SG CYS B 435 FE HEM B 501 1555 1555 2.26
LINK FE HEM B 501 O HOH B 755 1555 1555 2.26
SITE 1 AC1 23 ARG A 97 ILE A 112 VAL A 113 TRP A 120
SITE 2 AC1 23 ARG A 124 LEU A 294 ALA A 297 GLY A 298
SITE 3 AC1 23 THR A 301 THR A 302 GLN A 356 LEU A 361
SITE 4 AC1 23 LEU A 362 SER A 365 HIS A 368 PRO A 427
SITE 5 AC1 23 PHE A 428 SER A 429 ARG A 433 CYS A 435
SITE 6 AC1 23 GLY A 437 ALA A 441 HOH A 647
SITE 1 AC2 7 PHE A 100 THR A 364 SER A 365 PRO A 367
SITE 2 AC2 7 PHE A 476 SO4 A 503 HOH A 631
SITE 1 AC3 3 LEU A 208 GOL A 502 2QJ A 504
SITE 1 AC4 13 ALA A 106 ASN A 107 PHE A 114 LEU A 233
SITE 2 AC4 13 GLY A 296 THR A 301 THR A 304 LEU A 362
SITE 3 AC4 13 LEU A 366 ALA A 477 SO4 A 503 HOH A 681
SITE 4 AC4 13 HOH A 695
SITE 1 AC5 23 ARG B 97 ILE B 112 VAL B 113 TRP B 120
SITE 2 AC5 23 ARG B 124 LEU B 294 ALA B 297 GLY B 298
SITE 3 AC5 23 THR B 301 THR B 302 THR B 305 GLN B 356
SITE 4 AC5 23 LEU B 362 SER B 365 HIS B 368 PRO B 427
SITE 5 AC5 23 PHE B 428 SER B 429 ARG B 433 CYS B 435
SITE 6 AC5 23 GLY B 437 ALA B 441 HOH B 755
SITE 1 AC6 6 PHE B 100 THR B 364 SER B 365 PRO B 367
SITE 2 AC6 6 PHE B 476 SO4 B 503
SITE 1 AC7 4 LEU B 208 GOL B 502 2QJ B 504 HOH B 668
SITE 1 AC8 13 ASN B 107 PHE B 114 ILE B 205 VAL B 237
SITE 2 AC8 13 GLY B 296 GLU B 300 THR B 301 THR B 304
SITE 3 AC8 13 LEU B 362 ALA B 477 SO4 B 503 HOH B 682
SITE 4 AC8 13 HOH B 758
CRYST1 164.380 164.380 111.590 90.00 90.00 120.00 P 3 2 1 12
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 0.006083 0.003512 0.000000 0.00000
SCALE2 0.000000 0.007025 0.000000 0.00000
SCALE3 0.000000 0.000000 0.008961 0.00000
(ATOM LINES ARE NOT SHOWN.)
END
