HEADER OXIDOREDUCTASE 30-JAN-18 6FMD
TITLE TARGETING MYELOID DIFFERENTIATION USING POTENT HUMAN DIHYDROOROTATE
TITLE 2 DEHYDROGENASE (HDHODH) INHIBITORS BASED ON 2-HYDROXYPYRAZOLO[1,5-
TITLE 3 A]PYRIDINE SCAFFOLD
COMPND MOL_ID: 1;
COMPND 2 MOLECULE: DIHYDROOROTATE DEHYDROGENASE (QUINONE), MITOCHONDRIAL;
COMPND 3 CHAIN: A;
COMPND 4 SYNONYM: DHODEHASE,DIHYDROOROTATE OXIDASE;
COMPND 5 EC: 1.3.5.2;
COMPND 6 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: DHODH;
SOURCE 6 EXPRESSION_SYSTEM: ESCHERICHIA COLI BL21(DE3);
SOURCE 7 EXPRESSION_SYSTEM_TAXID: 469008
KEYWDS DHODH, INHIBITOR COMPLEX, OXIDOREDUCTASE
EXPDTA X-RAY DIFFRACTION
AUTHOR P.GOYAL,M.JARVA,M.ANDERSSON,M.L.LOLLI,R.FRIEMANN
REVDAT 4 17-JAN-24 6FMD 1 REMARK
REVDAT 3 08-AUG-18 6FMD 1 JRNL
REVDAT 2 18-JUL-18 6FMD 1 JRNL
REVDAT 1 11-JUL-18 6FMD 0
JRNL AUTH S.SAINAS,A.C.PIPPIONE,E.LUPINO,M.GIORGIS,P.CIRCOSTA,
JRNL AUTH 2 V.GAIDANO,P.GOYAL,D.BONANNI,B.ROLANDO,A.CIGNETTI,A.DUCIME,
JRNL AUTH 3 M.ANDERSSON,M.JARVA,R.FRIEMANN,M.PICCININI,C.RAMONDETTI,
JRNL AUTH 4 B.BUCCINNA,S.AL-KARADAGHI,D.BOSCHI,G.SAGLIO,M.L.LOLLI
JRNL TITL TARGETING MYELOID DIFFERENTIATION USING POTENT
JRNL TITL 2 2-HYDROXYPYRAZOLO[1,5- A]PYRIDINE SCAFFOLD-BASED HUMAN
JRNL TITL 3 DIHYDROOROTATE DEHYDROGENASE INHIBITORS.
JRNL REF J. MED. CHEM. V. 61 6034 2018
JRNL REFN ISSN 1520-4804
JRNL PMID 29939742
JRNL DOI 10.1021/ACS.JMEDCHEM.8B00373
REMARK 2
REMARK 2 RESOLUTION. 1.58 ANGSTROMS.
REMARK 3
REMARK 3 REFINEMENT.
REMARK 3 PROGRAM : REFMAC
REMARK 3 AUTHORS : MURSHUDOV,SKUBAK,LEBEDEV,PANNU,STEINER,
REMARK 3 : NICHOLLS,WINN,LONG,VAGIN
REMARK 3
REMARK 3 DATA USED IN REFINEMENT.
REMARK 3 RESOLUTION RANGE HIGH (ANGSTROMS) : 1.58
REMARK 3 RESOLUTION RANGE LOW (ANGSTROMS) : 78.32
REMARK 3 DATA CUTOFF (SIGMA(F)) : 0.000
REMARK 3 COMPLETENESS FOR RANGE (%) : 99.5
REMARK 3 NUMBER OF REFLECTIONS : 75404
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) : 0.138
REMARK 3 R VALUE (WORKING SET) : 0.137
REMARK 3 FREE R VALUE : 0.160
REMARK 3 FREE R VALUE TEST SET SIZE (%) : 5.100
REMARK 3 FREE R VALUE TEST SET COUNT : 4016
REMARK 3
REMARK 3 NUMBER OF NON-HYDROGEN ATOMS USED IN REFINEMENT.
REMARK 3 PROTEIN ATOMS : 2731
REMARK 3 NUCLEIC ACID ATOMS : 0
REMARK 3 HETEROGEN ATOMS : 181
REMARK 3 SOLVENT ATOMS : 155
REMARK 3
REMARK 3 B VALUES.
REMARK 3 FROM WILSON PLOT (A**2) : NULL
REMARK 3 MEAN B VALUE (OVERALL, A**2) : 26.41
REMARK 3 OVERALL ANISOTROPIC B VALUE.
REMARK 3 B11 (A**2) : 0.00000
REMARK 3 B22 (A**2) : 0.00000
REMARK 3 B33 (A**2) : 0.00000
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 OVERALL COORDINATE ERROR.
REMARK 3 ESU BASED ON R VALUE (A): 0.057
REMARK 3 ESU BASED ON FREE R VALUE (A): 0.052
REMARK 3 ESU BASED ON MAXIMUM LIKELIHOOD (A): 0.039
REMARK 3 ESU FOR B VALUES BASED ON MAXIMUM LIKELIHOOD (A**2): 2.644
REMARK 3
REMARK 3 RMS DEVIATIONS FROM IDEAL VALUES.
REMARK 3 DISTANCE RESTRAINTS. RMS SIGMA
REMARK 3 BOND LENGTH (A) : NULL ; NULL
REMARK 3 ANGLE DISTANCE (A) : NULL ; NULL
REMARK 3 INTRAPLANAR 1-4 DISTANCE (A) : NULL ; NULL
REMARK 3 H-BOND OR METAL COORDINATION (A) : NULL ; NULL
REMARK 3
REMARK 3 PLANE RESTRAINT (A) : NULL ; NULL
REMARK 3 CHIRAL-CENTER RESTRAINT (A**3) : NULL ; NULL
REMARK 3
REMARK 3 NON-BONDED CONTACT RESTRAINTS.
REMARK 3 SINGLE TORSION (A) : NULL ; NULL
REMARK 3 MULTIPLE TORSION (A) : NULL ; NULL
REMARK 3 H-BOND (X...Y) (A) : NULL ; NULL
REMARK 3 H-BOND (X-H...Y) (A) : NULL ; NULL
REMARK 3
REMARK 3 CONFORMATIONAL TORSION ANGLE RESTRAINTS.
REMARK 3 SPECIFIED (DEGREES) : NULL ; NULL
REMARK 3 PLANAR (DEGREES) : NULL ; NULL
REMARK 3 STAGGERED (DEGREES) : NULL ; NULL
REMARK 3 TRANSVERSE (DEGREES) : NULL ; 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 OTHER REFINEMENT REMARKS: HYDROGENS HAVE BEEN ADDED IN THE RIDING
REMARK 3 POSITIONS U VALUES : REFINED INDIVIDUALLY
REMARK 4
REMARK 4 6FMD COMPLIES WITH FORMAT V. 3.30, 13-JUL-11
REMARK 100
REMARK 100 THIS ENTRY HAS BEEN PROCESSED BY PDBE ON 31-JAN-18.
REMARK 100 THE DEPOSITION ID IS D_1200008579.
REMARK 200
REMARK 200 EXPERIMENTAL DETAILS
REMARK 200 EXPERIMENT TYPE : X-RAY DIFFRACTION
REMARK 200 DATE OF DATA COLLECTION : 08-APR-17
REMARK 200 TEMPERATURE (KELVIN) : 100
REMARK 200 PH : 5.2
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) : 0.97242
REMARK 200 MONOCHROMATOR : NULL
REMARK 200 OPTICS : NULL
REMARK 200
REMARK 200 DETECTOR TYPE : PIXEL
REMARK 200 DETECTOR MANUFACTURER : DECTRIS PILATUS 2M
REMARK 200 INTENSITY-INTEGRATION SOFTWARE : MOSFLM
REMARK 200 DATA SCALING SOFTWARE : SCALA 3.3.21
REMARK 200
REMARK 200 NUMBER OF UNIQUE REFLECTIONS : 79465
REMARK 200 RESOLUTION RANGE HIGH (A) : 1.580
REMARK 200 RESOLUTION RANGE LOW (A) : 78.324
REMARK 200 REJECTION CRITERIA (SIGMA(I)) : NULL
REMARK 200
REMARK 200 OVERALL.
REMARK 200 COMPLETENESS FOR RANGE (%) : 99.6
REMARK 200 DATA REDUNDANCY : 4.600
REMARK 200 R MERGE (I) : NULL
REMARK 200 R SYM (I) : 0.07100
REMARK 200 <I/SIGMA(I)> FOR THE DATA SET : 11.0000
REMARK 200
REMARK 200 IN THE HIGHEST RESOLUTION SHELL.
REMARK 200 HIGHEST RESOLUTION SHELL, RANGE HIGH (A) : 1.58
REMARK 200 HIGHEST RESOLUTION SHELL, RANGE LOW (A) : 1.67
REMARK 200 COMPLETENESS FOR SHELL (%) : 99.7
REMARK 200 DATA REDUNDANCY IN SHELL : 4.70
REMARK 200 R MERGE FOR SHELL (I) : 0.74000
REMARK 200 R SYM FOR SHELL (I) : 0.74000
REMARK 200 <I/SIGMA(I)> FOR SHELL : 1.000
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: 5MUT
REMARK 200
REMARK 200 REMARK: NULL
REMARK 280
REMARK 280 CRYSTAL
REMARK 280 SOLVENT CONTENT, VS (%): 63.47
REMARK 280 MATTHEWS COEFFICIENT, VM (ANGSTROMS**3/DA): 3.37
REMARK 280
REMARK 280 CRYSTALLIZATION CONDITIONS: 0.2M KBR, 0.2M KSCN, 0.1M NAAC PH 5.2,
REMARK 280 25% PEG 400, 2% PGA-LM, VAPOR DIFFUSION, HANGING DROP,
REMARK 280 TEMPERATURE 293K
REMARK 290
REMARK 290 CRYSTALLOGRAPHIC SYMMETRY
REMARK 290 SYMMETRY OPERATORS FOR SPACE GROUP: P 32 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+2/3
REMARK 290 3555 -X+Y,-X,Z+1/3
REMARK 290 4555 Y,X,-Z
REMARK 290 5555 X-Y,-Y,-Z+1/3
REMARK 290 6555 -X,-X+Y,-Z+2/3
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 81.63067
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 40.81533
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 40.81533
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 81.63067
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 TOTAL BURIED SURFACE AREA: 4790 ANGSTROM**2
REMARK 350 SURFACE AREA OF THE COMPLEX: 15040 ANGSTROM**2
REMARK 350 CHANGE IN SOLVENT FREE ENERGY: 13.0 KCAL/MOL
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 2
REMARK 465 ALA A 3
REMARK 465 TRP A 4
REMARK 465 ARG A 5
REMARK 465 HIS A 6
REMARK 465 LEU A 7
REMARK 465 LYS A 8
REMARK 465 LYS A 9
REMARK 465 ARG A 10
REMARK 465 ALA A 11
REMARK 465 GLN A 12
REMARK 465 ASP A 13
REMARK 465 ALA A 14
REMARK 465 VAL A 15
REMARK 465 ILE A 16
REMARK 465 ILE A 17
REMARK 465 LEU A 18
REMARK 465 GLY A 19
REMARK 465 GLY A 20
REMARK 465 GLY A 21
REMARK 465 GLY A 22
REMARK 465 LEU A 23
REMARK 465 LEU A 24
REMARK 465 PHE A 25
REMARK 465 ALA A 26
REMARK 465 SER A 27
REMARK 465 TYR A 28
REMARK 465 LEU A 29
REMARK 465 MET A 30
REMARK 465 ASN A 217
REMARK 465 THR A 218
REMARK 465 ALA A 219
REMARK 465 GLY A 220
REMARK 465 LEU A 221
REMARK 465 ARG A 222
REMARK 465 SER A 223
REMARK 465 LEU A 224
REMARK 465 GLN A 225
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 249 NE - CZ - NH1 ANGL. DEV. = 4.2 DEGREES
REMARK 500 ARG A 249 NE - CZ - NH2 ANGL. DEV. = -3.2 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 HIS A 41 -57.22 -126.04
REMARK 500 ASP A 99 78.62 -100.36
REMARK 500 ALA A 104 23.82 -140.76
REMARK 500 TYR A 356 -64.10 -144.36
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 DUH A 401
REMARK 800
REMARK 800 SITE_IDENTIFIER: AC2
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: binding site for residue CL A 402
REMARK 800
REMARK 800 SITE_IDENTIFIER: AC3
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: binding site for residue CL A 403
REMARK 800
REMARK 800 SITE_IDENTIFIER: AC4
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: binding site for residue FMN A 404
REMARK 800
REMARK 800 SITE_IDENTIFIER: AC5
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: binding site for residue ACT A 405
REMARK 800
REMARK 800 SITE_IDENTIFIER: AC6
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: binding site for residue ACT A 406
REMARK 800
REMARK 800 SITE_IDENTIFIER: AC7
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: binding site for residue ACT A 407
REMARK 800
REMARK 800 SITE_IDENTIFIER: AC8
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: binding site for residue ACT A 408
REMARK 800
REMARK 800 SITE_IDENTIFIER: AC9
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: binding site for residue ACT A 409
REMARK 800
REMARK 800 SITE_IDENTIFIER: AD1
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: binding site for residue ACT A 410
REMARK 800
REMARK 800 SITE_IDENTIFIER: AD2
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: binding site for residue ORO A 411
REMARK 800
REMARK 800 SITE_IDENTIFIER: AD3
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: binding site for residue GOL A 412
REMARK 800
REMARK 800 SITE_IDENTIFIER: AD4
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: binding site for residue GOL A 413
REMARK 800
REMARK 800 SITE_IDENTIFIER: AD5
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: binding site for residue GOL A 414
REMARK 800
REMARK 800 SITE_IDENTIFIER: AD6
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: binding site for residue GOL A 415
REMARK 800
REMARK 800 SITE_IDENTIFIER: AD7
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: binding site for residue PGE A 416
REMARK 800
REMARK 800 SITE_IDENTIFIER: AD8
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: binding site for residue PGE A 417
REMARK 800
REMARK 800 SITE_IDENTIFIER: AD9
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: binding site for residue PGE A 418
REMARK 800
REMARK 800 SITE_IDENTIFIER: AE1
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: binding site for residue PGE A 419
REMARK 800
REMARK 800 SITE_IDENTIFIER: AE2
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: binding site for residue PGE A 420
REMARK 800
REMARK 800 SITE_IDENTIFIER: AE3
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: binding site for residue PGE A 421
DBREF 6FMD A 2 396 UNP Q02127 PYRD_HUMAN 1 395
SEQRES 1 A 395 MET ALA TRP ARG HIS LEU LYS LYS ARG ALA GLN ASP ALA
SEQRES 2 A 395 VAL ILE ILE LEU GLY GLY GLY GLY LEU LEU PHE ALA SER
SEQRES 3 A 395 TYR LEU MET ALA THR GLY ASP GLU ARG PHE TYR ALA GLU
SEQRES 4 A 395 HIS LEU MET PRO THR LEU GLN GLY LEU LEU ASP PRO GLU
SEQRES 5 A 395 SER ALA HIS ARG LEU ALA VAL ARG PHE THR SER LEU GLY
SEQRES 6 A 395 LEU LEU PRO ARG ALA ARG PHE GLN ASP SER ASP MET LEU
SEQRES 7 A 395 GLU VAL ARG VAL LEU GLY HIS LYS PHE ARG ASN PRO VAL
SEQRES 8 A 395 GLY ILE ALA ALA GLY PHE ASP LYS HIS GLY GLU ALA VAL
SEQRES 9 A 395 ASP GLY LEU TYR LYS MET GLY PHE GLY PHE VAL GLU ILE
SEQRES 10 A 395 GLY SER VAL THR PRO LYS PRO GLN GLU GLY ASN PRO ARG
SEQRES 11 A 395 PRO ARG VAL PHE ARG LEU PRO GLU ASP GLN ALA VAL ILE
SEQRES 12 A 395 ASN ARG TYR GLY PHE ASN SER HIS GLY LEU SER VAL VAL
SEQRES 13 A 395 GLU HIS ARG LEU ARG ALA ARG GLN GLN LYS GLN ALA LYS
SEQRES 14 A 395 LEU THR GLU ASP GLY LEU PRO LEU GLY VAL ASN LEU GLY
SEQRES 15 A 395 LYS ASN LYS THR SER VAL ASP ALA ALA GLU ASP TYR ALA
SEQRES 16 A 395 GLU GLY VAL ARG VAL LEU GLY PRO LEU ALA ASP TYR LEU
SEQRES 17 A 395 VAL VAL ASN VAL SER SER PRO ASN THR ALA GLY LEU ARG
SEQRES 18 A 395 SER LEU GLN GLY LYS ALA GLU LEU ARG ARG LEU LEU THR
SEQRES 19 A 395 LYS VAL LEU GLN GLU ARG ASP GLY LEU ARG ARG VAL HIS
SEQRES 20 A 395 ARG PRO ALA VAL LEU VAL LYS ILE ALA PRO ASP LEU THR
SEQRES 21 A 395 SER GLN ASP LYS GLU ASP ILE ALA SER VAL VAL LYS GLU
SEQRES 22 A 395 LEU GLY ILE ASP GLY LEU ILE VAL THR ASN THR THR VAL
SEQRES 23 A 395 SER ARG PRO ALA GLY LEU GLN GLY ALA LEU ARG SER GLU
SEQRES 24 A 395 THR GLY GLY LEU SER GLY LYS PRO LEU ARG ASP LEU SER
SEQRES 25 A 395 THR GLN THR ILE ARG GLU MET TYR ALA LEU THR GLN GLY
SEQRES 26 A 395 ARG VAL PRO ILE ILE GLY VAL GLY GLY VAL SER SER GLY
SEQRES 27 A 395 GLN ASP ALA LEU GLU LYS ILE ARG ALA GLY ALA SER LEU
SEQRES 28 A 395 VAL GLN LEU TYR THR ALA LEU THR PHE TRP GLY PRO PRO
SEQRES 29 A 395 VAL VAL GLY LYS VAL LYS ARG GLU LEU GLU ALA LEU LEU
SEQRES 30 A 395 LYS GLU GLN GLY PHE GLY GLY VAL THR ASP ALA ILE GLY
SEQRES 31 A 395 ALA ASP HIS ARG ARG
HET DUH A 401 29
HET CL A 402 1
HET CL A 403 1
HET FMN A 404 31
HET ACT A 405 4
HET ACT A 406 4
HET ACT A 407 4
HET ACT A 408 4
HET ACT A 409 4
HET ACT A 410 4
HET ORO A 411 11
HET GOL A 412 6
HET GOL A 413 6
HET GOL A 414 6
HET GOL A 415 6
HET PGE A 416 10
HET PGE A 417 10
HET PGE A 418 10
HET PGE A 419 10
HET PGE A 420 10
HET PGE A 421 10
HETNAM DUH 2-OXIDANYL-~{N}-[2,3,5,6-TETRAKIS(FLUORANYL)-4-PHENYL-
HETNAM 2 DUH PHENYL]PYRAZOLO[1,5-A]PYRIDINE-3-CARBOXAMIDE
HETNAM CL CHLORIDE ION
HETNAM FMN FLAVIN MONONUCLEOTIDE
HETNAM ACT ACETATE ION
HETNAM ORO OROTIC ACID
HETNAM GOL GLYCEROL
HETNAM PGE TRIETHYLENE GLYCOL
HETSYN FMN RIBOFLAVIN MONOPHOSPHATE
HETSYN GOL GLYCERIN; PROPANE-1,2,3-TRIOL
FORMUL 2 DUH C20 H11 F4 N3 O2
FORMUL 3 CL 2(CL 1-)
FORMUL 5 FMN C17 H21 N4 O9 P
FORMUL 6 ACT 6(C2 H3 O2 1-)
FORMUL 12 ORO C5 H4 N2 O4
FORMUL 13 GOL 4(C3 H8 O3)
FORMUL 17 PGE 6(C6 H14 O4)
FORMUL 23 HOH *155(H2 O)
HELIX 1 AA1 THR A 32 HIS A 41 1 10
HELIX 2 AA2 HIS A 41 LEU A 50 1 10
HELIX 3 AA3 ASP A 51 LEU A 65 1 15
HELIX 4 AA4 SER A 76 GLU A 80 5 5
HELIX 5 AA5 ALA A 104 MET A 111 1 8
HELIX 6 AA6 PRO A 138 ASP A 140 5 3
HELIX 7 AA7 GLY A 153 ALA A 163 1 11
HELIX 8 AA8 ARG A 164 ASP A 174 1 11
HELIX 9 AA9 ASP A 190 GLY A 203 1 14
HELIX 10 AB1 PRO A 204 ALA A 206 5 3
HELIX 11 AB2 LYS A 227 GLY A 243 1 17
HELIX 12 AB3 LEU A 244 ARG A 249 5 6
HELIX 13 AB4 THR A 261 GLY A 276 1 16
HELIX 14 AB5 LEU A 309 THR A 324 1 16
HELIX 15 AB6 SER A 338 GLY A 349 1 12
HELIX 16 AB7 TYR A 356 GLY A 363 1 8
HELIX 17 AB8 PRO A 365 GLN A 381 1 17
HELIX 18 AB9 GLY A 385 ILE A 390 1 6
HELIX 19 AC1 GLY A 391 ARG A 396 5 6
SHEET 1 AA1 2 VAL A 81 VAL A 83 0
SHEET 2 AA1 2 HIS A 86 PHE A 88 -1 O PHE A 88 N VAL A 81
SHEET 1 AA2 9 VAL A 92 ILE A 94 0
SHEET 2 AA2 9 PHE A 115 VAL A 121 1 O PHE A 115 N ILE A 94
SHEET 3 AA2 9 LEU A 178 LEU A 182 1 O GLY A 179 N VAL A 116
SHEET 4 AA2 9 TYR A 208 VAL A 213 1 O VAL A 210 N LEU A 182
SHEET 5 AA2 9 ALA A 251 ILE A 256 1 O LYS A 255 N VAL A 213
SHEET 6 AA2 9 GLY A 279 VAL A 282 1 O ILE A 281 N VAL A 254
SHEET 7 AA2 9 ILE A 330 VAL A 333 1 O ILE A 331 N VAL A 282
SHEET 8 AA2 9 LEU A 352 LEU A 355 1 O LEU A 352 N GLY A 332
SHEET 9 AA2 9 VAL A 92 ILE A 94 1 N GLY A 93 O VAL A 353
SHEET 1 AA3 3 VAL A 134 LEU A 137 0
SHEET 2 AA3 3 ALA A 142 ASN A 145 -1 O ALA A 142 N LEU A 137
SHEET 3 AA3 3 GLY A 303 GLY A 306 -1 O GLY A 303 N ASN A 145
CISPEP 1 GLY A 119 SER A 120 0 5.30
CISPEP 2 ARG A 131 PRO A 132 0 0.19
CISPEP 3 VAL A 282 THR A 283 0 12.28
SITE 1 AC1 17 MET A 43 LEU A 46 GLN A 47 PRO A 52
SITE 2 AC1 17 ALA A 55 HIS A 56 ALA A 59 PHE A 62
SITE 3 AC1 17 LEU A 67 LEU A 68 VAL A 134 ARG A 136
SITE 4 AC1 17 TYR A 356 LEU A 359 THR A 360 PRO A 364
SITE 5 AC1 17 HOH A 597
SITE 1 AC2 4 GLN A 165 PRO A 204 ARG A 298 SER A 299
SITE 1 AC3 3 ARG A 245 THR A 301 GLY A 302
SITE 1 AC4 25 ALA A 95 ALA A 96 GLY A 97 LYS A 100
SITE 2 AC4 25 GLY A 119 SER A 120 ASN A 145 ASN A 181
SITE 3 AC4 25 ASN A 212 LYS A 255 THR A 283 ASN A 284
SITE 4 AC4 25 THR A 285 SER A 305 GLY A 306 LEU A 309
SITE 5 AC4 25 VAL A 333 GLY A 334 GLY A 335 LEU A 355
SITE 6 AC4 25 TYR A 356 THR A 357 ORO A 411 HOH A 522
SITE 7 AC4 25 HOH A 533
SITE 1 AC5 5 ALA A 169 THR A 172 LEU A 205 ASP A 207
SITE 2 AC5 5 HOH A 517
SITE 1 AC6 3 ARG A 241 ASP A 242 LEU A 275
SITE 1 AC7 1 ARG A 246
SITE 1 AC8 7 LYS A 307 PRO A 308 ASP A 311 THR A 314
SITE 2 AC8 7 GLN A 315 ARG A 318 HOH A 507
SITE 1 AC9 1 HIS A 41
SITE 1 AD1 4 GLN A 239 ASP A 242 GLY A 243 HOH A 503
SITE 1 AD2 9 LYS A 100 ASN A 145 TYR A 147 GLY A 148
SITE 2 AD2 9 PHE A 149 ASN A 212 ASN A 284 THR A 285
SITE 3 AD2 9 FMN A 404
SITE 1 AD3 4 GLY A 276 ARG A 327 HOH A 526 HOH A 565
SITE 1 AD4 3 TYR A 109 LYS A 110 HOH A 603
SITE 1 AD5 3 GLU A 127 ASN A 129 ARG A 131
SITE 1 AD6 3 LYS A 124 SER A 155 GLU A 197
SITE 1 AD7 6 HIS A 101 GLN A 126 GLU A 127 ASN A 150
SITE 2 AD7 6 SER A 151 PGE A 417
SITE 1 AD8 3 HIS A 152 ARG A 160 PGE A 416
SITE 1 AD9 4 ASP A 51 SER A 54 ARG A 57 HOH A 505
SITE 1 AE1 3 ARG A 82 GLY A 326 SER A 351
SITE 1 AE2 6 ARG A 246 ARG A 249 ASP A 278 HOH A 521
SITE 2 AE2 6 HOH A 567 HOH A 574
SITE 1 AE3 4 ARG A 245 VAL A 287 SER A 288 ARG A 289
CRYST1 90.441 90.441 122.446 90.00 90.00 120.00 P 32 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 0.011057 0.006384 0.000000 0.00000
SCALE2 0.000000 0.012767 0.000000 0.00000
SCALE3 0.000000 0.000000 0.008167 0.00000
(ATOM LINES ARE NOT SHOWN.)
END
