HEADER OXIDOREDUCTASE 13-NOV-07 3BCJ
TITLE CRYSTAL STRUCTURE OF ALDOSE REDUCTASE COMPLEXED WITH 2S4R
TITLE 2 (STEREOISOMER OF FIDARESTAT, 2S4S) AT 0.78 A
COMPND MOL_ID: 1;
COMPND 2 MOLECULE: ALDOSE REDUCTASE;
COMPND 3 CHAIN: A;
COMPND 4 FRAGMENT: HUMAN ALDOSE REDUCTASE;
COMPND 5 SYNONYM: AR, ALDEHYDE REDUCTASE;
COMPND 6 EC: 1.1.1.21;
COMPND 7 ENGINEERED: YES
SOURCE MOL_ID: 1;
SOURCE 2 ORGANISM_SCIENTIFIC: HOMO SAPIENS;
SOURCE 3 ORGANISM_COMMON: HUMAN;
SOURCE 4 ORGANISM_TAXID: 9606;
SOURCE 5 EXPRESSION_SYSTEM: ESCHERICHIA COLI BL21;
SOURCE 6 EXPRESSION_SYSTEM_TAXID: 511693;
SOURCE 7 EXPRESSION_SYSTEM_STRAIN: BL21;
SOURCE 8 EXPRESSION_SYSTEM_VECTOR_TYPE: PLASMID;
SOURCE 9 EXPRESSION_SYSTEM_PLASMID: PET15B
KEYWDS ALDO-KETO REDUCTASES, DIABETES, DRUG DESIGN, POLYL PATHWAY,
KEYWDS 2 ACETYLATION, CATARACT, CYTOPLASM, NADP, OXIDOREDUCTASE, POLYMORPHISM
EXPDTA X-RAY DIFFRACTION
AUTHOR H.T.ZHAO,O.EL-KABBANI
REVDAT 3 01-NOV-23 3BCJ 1 REMARK
REVDAT 2 24-FEB-09 3BCJ 1 VERSN
REVDAT 1 08-APR-08 3BCJ 0
JRNL AUTH H.T.ZHAO,I.HAZEMANN,A.MITSCHLER,V.CARBONE,A.JOACHIMIAK,
JRNL AUTH 2 S.GINELL,A.PODJARNY,O.EL-KABBANI
JRNL TITL UNUSUAL BINDING MODE OF THE 2S4R STEREOISOMER OF THE POTENT
JRNL TITL 2 ALDOSE REDUCTASE CYCLIC IMIDE INHIBITOR FIDARESTAT (2S4S) IN
JRNL TITL 3 THE 15 K CRYSTAL STRUCTURE OF THE TERNARY COMPLEX REFINED AT
JRNL TITL 4 0.78 A RESOLUTION: IMPLICATIONS FOR THE INHIBITION MECHANISM
JRNL REF J.MED.CHEM. V. 51 1478 2008
JRNL REFN ISSN 0022-2623
JRNL PMID 18284183
JRNL DOI 10.1021/JM701514K
REMARK 2
REMARK 2 RESOLUTION. 0.78 ANGSTROMS.
REMARK 3
REMARK 3 REFINEMENT.
REMARK 3 PROGRAM : SHELXL-97
REMARK 3 AUTHORS : G.M.SHELDRICK
REMARK 3
REMARK 3 DATA USED IN REFINEMENT.
REMARK 3 RESOLUTION RANGE HIGH (ANGSTROMS) : 0.78
REMARK 3 RESOLUTION RANGE LOW (ANGSTROMS) : 10.00
REMARK 3 DATA CUTOFF (SIGMA(F)) : 0.000
REMARK 3 COMPLETENESS FOR RANGE (%) : 92.5
REMARK 3 CROSS-VALIDATION METHOD : NULL
REMARK 3 FREE R VALUE TEST SET SELECTION : NULL
REMARK 3
REMARK 3 FIT TO DATA USED IN REFINEMENT (NO CUTOFF).
REMARK 3 R VALUE (WORKING + TEST SET, NO CUTOFF) : 0.105
REMARK 3 R VALUE (WORKING SET, NO CUTOFF) : 0.101
REMARK 3 FREE R VALUE (NO CUTOFF) : 0.110
REMARK 3 FREE R VALUE TEST SET SIZE (%, NO CUTOFF) : 5.000
REMARK 3 FREE R VALUE TEST SET COUNT (NO CUTOFF) : 16809
REMARK 3 TOTAL NUMBER OF REFLECTIONS (NO CUTOFF) : 319354
REMARK 3
REMARK 3 FIT/AGREEMENT OF MODEL FOR DATA WITH F>4SIG(F).
REMARK 3 R VALUE (WORKING + TEST SET, F>4SIG(F)) : 0.101
REMARK 3 R VALUE (WORKING SET, F>4SIG(F)) : NULL
REMARK 3 FREE R VALUE (F>4SIG(F)) : NULL
REMARK 3 FREE R VALUE TEST SET SIZE (%, F>4SIG(F)) : NULL
REMARK 3 FREE R VALUE TEST SET COUNT (F>4SIG(F)) : NULL
REMARK 3 TOTAL NUMBER OF REFLECTIONS (F>4SIG(F)) : 303890
REMARK 3
REMARK 3 NUMBER OF NON-HYDROGEN ATOMS USED IN REFINEMENT.
REMARK 3 PROTEIN ATOMS : 2525
REMARK 3 NUCLEIC ACID ATOMS : 0
REMARK 3 HETEROGEN ATOMS : 81
REMARK 3 SOLVENT ATOMS : 684
REMARK 3
REMARK 3 MODEL REFINEMENT.
REMARK 3 OCCUPANCY SUM OF NON-HYDROGEN ATOMS : 3204.1
REMARK 3 OCCUPANCY SUM OF HYDROGEN ATOMS : 2435.2
REMARK 3 NUMBER OF DISCRETELY DISORDERED RESIDUES : 109
REMARK 3 NUMBER OF LEAST-SQUARES PARAMETERS : 32941
REMARK 3 NUMBER OF RESTRAINTS : 8836
REMARK 3
REMARK 3 RMS DEVIATIONS FROM RESTRAINT TARGET VALUES.
REMARK 3 BOND LENGTHS (A) : 0.018
REMARK 3 ANGLE DISTANCES (A) : 0.035
REMARK 3 SIMILAR DISTANCES (NO TARGET VALUES) (A) : 0.000
REMARK 3 DISTANCES FROM RESTRAINT PLANES (A) : 0.031
REMARK 3 ZERO CHIRAL VOLUMES (A**3) : 0.111
REMARK 3 NON-ZERO CHIRAL VOLUMES (A**3) : 0.119
REMARK 3 ANTI-BUMPING DISTANCE RESTRAINTS (A) : 0.000
REMARK 3 RIGID-BOND ADP COMPONENTS (A**2) : 0.000
REMARK 3 SIMILAR ADP COMPONENTS (A**2) : 0.000
REMARK 3 APPROXIMATELY ISOTROPIC ADPS (A**2) : 0.000
REMARK 3
REMARK 3 BULK SOLVENT MODELING.
REMARK 3 METHOD USED: NULL
REMARK 3
REMARK 3 STEREOCHEMISTRY TARGET VALUES : ENGH & HUBER
REMARK 3 SPECIAL CASE: NULL
REMARK 3
REMARK 3 OTHER REFINEMENT REMARKS: THE CLOSE CONTACTS ARE DUE TO EITHER
REMARK 3 DOUBLE CONFORMATION OF AMINO ACID SIDE CHAINS OR PARTIAL
REMARK 3 OCCUPANCIES BY WATER MOLECULES OBSERVED AT VERY HIGH RESOLUTION.
REMARK 4
REMARK 4 3BCJ COMPLIES WITH FORMAT V. 3.30, 13-JUL-11
REMARK 100
REMARK 100 THIS ENTRY HAS BEEN PROCESSED BY PDBJ ON 16-NOV-07.
REMARK 100 THE DEPOSITION ID IS D_1000045352.
REMARK 200
REMARK 200 EXPERIMENTAL DETAILS
REMARK 200 EXPERIMENT TYPE : X-RAY DIFFRACTION
REMARK 200 DATE OF DATA COLLECTION : 01-MAR-05
REMARK 200 TEMPERATURE (KELVIN) : 15
REMARK 200 PH : 5
REMARK 200 NUMBER OF CRYSTALS USED : 1
REMARK 200
REMARK 200 SYNCHROTRON (Y/N) : Y
REMARK 200 RADIATION SOURCE : APS
REMARK 200 BEAMLINE : 19-ID
REMARK 200 X-RAY GENERATOR MODEL : NULL
REMARK 200 MONOCHROMATIC OR LAUE (M/L) : M
REMARK 200 WAVELENGTH OR RANGE (A) : 0.9
REMARK 200 MONOCHROMATOR : MIRRORS
REMARK 200 OPTICS : NULL
REMARK 200
REMARK 200 DETECTOR TYPE : CCD
REMARK 200 DETECTOR MANUFACTURER : CUSTOM-MADE
REMARK 200 INTENSITY-INTEGRATION SOFTWARE : HKL-2000
REMARK 200 DATA SCALING SOFTWARE : SCALEPACK
REMARK 200
REMARK 200 NUMBER OF UNIQUE REFLECTIONS : 336314
REMARK 200 RESOLUTION RANGE HIGH (A) : 0.780
REMARK 200 RESOLUTION RANGE LOW (A) : 99.000
REMARK 200 REJECTION CRITERIA (SIGMA(I)) : 2.000
REMARK 200
REMARK 200 OVERALL.
REMARK 200 COMPLETENESS FOR RANGE (%) : 97.3
REMARK 200 DATA REDUNDANCY : 2.120
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) : 0.78
REMARK 200 HIGHEST RESOLUTION SHELL, RANGE LOW (A) : 0.81
REMARK 200 COMPLETENESS FOR SHELL (%) : 93.3
REMARK 200 DATA REDUNDANCY IN SHELL : 2.00
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: SHELX
REMARK 200 STARTING MODEL: 1PWN
REMARK 200
REMARK 200 REMARK: NULL
REMARK 280
REMARK 280 CRYSTAL
REMARK 280 SOLVENT CONTENT, VS (%): 43.01
REMARK 280 MATTHEWS COEFFICIENT, VM (ANGSTROMS**3/DA): 2.16
REMARK 280
REMARK 280 CRYSTALLIZATION CONDITIONS: PEG 6000, AMMONIUM CITRATE, PH 5,
REMARK 280 VAPOR DIFFUSION, HANGING DROP, TEMPERATURE 277K
REMARK 290
REMARK 290 CRYSTALLOGRAPHIC SYMMETRY
REMARK 290 SYMMETRY OPERATORS FOR SPACE GROUP: P 1 21 1
REMARK 290
REMARK 290 SYMOP SYMMETRY
REMARK 290 NNNMMM OPERATOR
REMARK 290 1555 X,Y,Z
REMARK 290 2555 -X,Y+1/2,-Z
REMARK 290
REMARK 290 WHERE NNN -> OPERATOR NUMBER
REMARK 290 MMM -> TRANSLATION VECTOR
REMARK 290
REMARK 290 CRYSTALLOGRAPHIC SYMMETRY TRANSFORMATIONS
REMARK 290 THE FOLLOWING TRANSFORMATIONS OPERATE ON THE ATOM/HETATM
REMARK 290 RECORDS IN THIS ENTRY TO PRODUCE CRYSTALLOGRAPHICALLY
REMARK 290 RELATED MOLECULES.
REMARK 290 SMTRY1 1 1.000000 0.000000 0.000000 0.00000
REMARK 290 SMTRY2 1 0.000000 1.000000 0.000000 0.00000
REMARK 290 SMTRY3 1 0.000000 0.000000 1.000000 0.00000
REMARK 290 SMTRY1 2 -1.000000 0.000000 0.000000 0.00000
REMARK 290 SMTRY2 2 0.000000 1.000000 0.000000 33.32100
REMARK 290 SMTRY3 2 0.000000 0.000000 -1.000000 0.00000
REMARK 290
REMARK 290 REMARK: NULL
REMARK 300
REMARK 300 BIOMOLECULE: 1
REMARK 300 SEE REMARK 350 FOR THE AUTHOR PROVIDED AND/OR PROGRAM
REMARK 300 GENERATED ASSEMBLY INFORMATION FOR THE STRUCTURE IN
REMARK 300 THIS ENTRY. THE REMARK MAY ALSO PROVIDE INFORMATION ON
REMARK 300 BURIED SURFACE AREA.
REMARK 350
REMARK 350 COORDINATES FOR A COMPLETE MULTIMER REPRESENTING THE KNOWN
REMARK 350 BIOLOGICALLY SIGNIFICANT OLIGOMERIZATION STATE OF THE
REMARK 350 MOLECULE CAN BE GENERATED BY APPLYING BIOMT TRANSFORMATIONS
REMARK 350 GIVEN BELOW. BOTH NON-CRYSTALLOGRAPHIC AND
REMARK 350 CRYSTALLOGRAPHIC OPERATIONS ARE GIVEN.
REMARK 350
REMARK 350 BIOMOLECULE: 1
REMARK 350 AUTHOR DETERMINED BIOLOGICAL UNIT: MONOMERIC
REMARK 350 SOFTWARE DETERMINED QUATERNARY STRUCTURE: MONOMERIC
REMARK 350 SOFTWARE USED: PISA
REMARK 350 APPLY THE FOLLOWING TO CHAINS: A
REMARK 350 BIOMT1 1 1.000000 0.000000 0.000000 0.00000
REMARK 350 BIOMT2 1 0.000000 1.000000 0.000000 0.00000
REMARK 350 BIOMT3 1 0.000000 0.000000 1.000000 0.00000
REMARK 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 O HOH A 1097 O HOH A 1679 1.17
REMARK 500 C HIS A 312 O HOH A 1677 1.24
REMARK 500 O HOH A 1295 O HOH A 1684 1.28
REMARK 500 CE LYS A 239 O HOH A 1648 1.32
REMARK 500 NZ LYS A 154 O HOH A 1630 1.34
REMARK 500 O HOH A 1338 O HOH A 1660 1.41
REMARK 500 CB SER A 282 O HOH A 1621 1.42
REMARK 500 CB SER A 282 O HOH A 1673 1.43
REMARK 500 NE2 HIS A 163 O HOH A 1635 1.43
REMARK 500 CG MET A 0 O HOH A 1682 1.51
REMARK 500 OE1 GLN A 26 O HOH A 1613 1.51
REMARK 500 O HOH A 1326 O HOH A 1651 1.52
REMARK 500 O HIS A 312 O HOH A 1677 1.57
REMARK 500 NE2 GLN A 26 O HOH A 1609 1.59
REMARK 500 CB MET A 0 O HOH A 1682 1.61
REMARK 500 N GLU A 84 O HOH A 1605 1.65
REMARK 500 NZ LYS A 239 O HOH A 1648 1.67
REMARK 500 O4 CIT A 319 O HOH A 1663 1.68
REMARK 500 SD MET A 0 O HOH A 1682 1.68
REMARK 500 CG MET A 0 O HOH A 1682 1.69
REMARK 500 N GLU A 313 O HOH A 1677 1.70
REMARK 500 O HOH A 1443 O HOH A 1647 1.72
REMARK 500 O HOH A 1144 O HOH A 1660 1.73
REMARK 500 C HIS A 83 O HOH A 1605 1.73
REMARK 500 O HOH A 1337 O HOH A 1678 1.78
REMARK 500 CD ARG A 293 O HOH A 1655 1.79
REMARK 500 O HOH A 1658 O HOH A 1659 1.80
REMARK 500 O HOH A 1284 O HOH A 1618 1.82
REMARK 500 CB ARG A 293 O HOH A 1655 1.83
REMARK 500 O HOH A 1373 O HOH A 1667 1.86
REMARK 500 O HOH A 1404 O HOH A 1513 1.91
REMARK 500 O HOH A 1624 O HOH A 1653 1.95
REMARK 500 O HOH A 1412 O HOH A 1435 1.97
REMARK 500 OE2 GLU A 29 O HOH A 1269 1.99
REMARK 500 O HOH A 1517 O HOH A 1652 1.99
REMARK 500 O HOH A 1471 O HOH A 1617 2.01
REMARK 500 O HOH A 1014 O HOH A 1558 2.01
REMARK 500 SD MET A 0 O HOH A 1682 2.03
REMARK 500 O HOH A 1453 O HOH A 1497 2.03
REMARK 500 OD1 ASP A 102 O HOH A 1368 2.04
REMARK 500 OE2 GLU A 120 O HOH A 1138 2.04
REMARK 500 CD2 LEU A 99 CD1 LEU A 101 2.06
REMARK 500 CG2 ILE A 137 O HOH A 1641 2.07
REMARK 500 O HOH A 1621 O HOH A 1673 2.08
REMARK 500 NH2 ARG A 293 O HOH A 1627 2.08
REMARK 500 O GLU A 313 O HOH A 1677 2.10
REMARK 500 CD ARG A 293 O HOH A 1655 2.11
REMARK 500 O HOH A 1175 O HOH A 1558 2.11
REMARK 500 CD2 HIS A 163 O HOH A 1635 2.12
REMARK 500 CD1 LEU A 164 O HOH A 1438 2.13
REMARK 500
REMARK 500 THIS ENTRY HAS 64 CLOSE CONTACTS
REMARK 500
REMARK 500 REMARK: NULL
REMARK 500
REMARK 500 GEOMETRY AND STEREOCHEMISTRY
REMARK 500 SUBTOPIC: CLOSE CONTACTS
REMARK 500
REMARK 500 THE FOLLOWING ATOMS THAT ARE RELATED BY CRYSTALLOGRAPHIC
REMARK 500 SYMMETRY ARE IN CLOSE CONTACT. AN ATOM LOCATED WITHIN 0.15
REMARK 500 ANGSTROMS OF A SYMMETRY RELATED ATOM IS ASSUMED TO BE ON A
REMARK 500 SPECIAL POSITION AND IS, THEREFORE, LISTED IN REMARK 375
REMARK 500 INSTEAD OF REMARK 500. ATOMS WITH NON-BLANK ALTERNATE
REMARK 500 LOCATION INDICATORS ARE NOT INCLUDED IN THE CALCULATIONS.
REMARK 500
REMARK 500 DISTANCE CUTOFF:
REMARK 500 2.2 ANGSTROMS FOR CONTACTS NOT INVOLVING HYDROGEN ATOMS
REMARK 500 1.6 ANGSTROMS FOR CONTACTS INVOLVING HYDROGEN ATOMS
REMARK 500
REMARK 500 ATM1 RES C SSEQI ATM2 RES C SSEQI SSYMOP DISTANCE
REMARK 500 NH1 ARG A 293 O HOH A 1204 1655 0.71
REMARK 500 O HOH A 1627 O HOH A 1649 1655 1.60
REMARK 500 CZ ARG A 293 O HOH A 1204 1655 1.80
REMARK 500 O HOH A 1654 O HOH A 1665 1556 1.97
REMARK 500 O HOH A 1408 O HOH A 1502 2556 1.99
REMARK 500 O HOH A 1471 O HOH A 1499 2546 2.18
REMARK 500 NE2 GLN A 26 O HOH A 1457 2646 2.19
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 LYS A 100 40.50 74.81
REMARK 500
REMARK 500 REMARK: NULL
REMARK 500
REMARK 500 GEOMETRY AND STEREOCHEMISTRY
REMARK 500 SUBTOPIC: PLANAR GROUPS
REMARK 500
REMARK 500 PLANAR GROUPS IN THE FOLLOWING RESIDUES HAVE A TOTAL
REMARK 500 RMS DISTANCE OF ALL ATOMS FROM THE BEST-FIT PLANE
REMARK 500 BY MORE THAN AN EXPECTED VALUE OF 6*RMSD, WITH AN
REMARK 500 RMSD 0.02 ANGSTROMS, OR AT LEAST ONE ATOM HAS
REMARK 500 AN RMSD GREATER THAN THIS VALUE
REMARK 500 (M=MODEL NUMBER; RES=RESIDUE NAME; C=CHAIN IDENTIFIER;
REMARK 500 SSEQ=SEQUENCE NUMBER; I=INSERTION CODE).
REMARK 500
REMARK 500 M RES CSSEQI RMS TYPE
REMARK 500 ARG A 63 0.23 SIDE CHAIN
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 NAP A 318
REMARK 800
REMARK 800 SITE_IDENTIFIER: AC2
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: BINDING SITE FOR RESIDUE CIT A 319
REMARK 800
REMARK 800 SITE_IDENTIFIER: AC3
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: BINDING SITE FOR RESIDUE FIS A 320
REMARK 900
REMARK 900 RELATED ENTRIES
REMARK 900 RELATED ID: 1X98 RELATED DB: PDB
REMARK 900 SAME STRUCTURE AT 1.3 A
REMARK 900 RELATED ID: 1PWM RELATED DB: PDB
REMARK 900 SAME PROTEIN WITH FIDARESTAT (2S4S)
REMARK 999
REMARK 999 SEQUENCE
REMARK 999 FOR THIS CONFLICT, REFER TO REFERENCE 2 IN THE DATABASE,
REMARK 999 ALDR_HUMAN, P15121
DBREF 3BCJ A 0 315 UNP P15121 ALDR_HUMAN 1 316
SEQADV 3BCJ ILE A 4 UNP P15121 LEU 5 SEE REMARK 999
SEQRES 1 A 316 MET ALA SER ARG ILE LEU LEU ASN ASN GLY ALA LYS MET
SEQRES 2 A 316 PRO ILE LEU GLY LEU GLY THR TRP LYS SER PRO PRO GLY
SEQRES 3 A 316 GLN VAL THR GLU ALA VAL LYS VAL ALA ILE ASP VAL GLY
SEQRES 4 A 316 TYR ARG HIS ILE ASP CYS ALA HIS VAL TYR GLN ASN GLU
SEQRES 5 A 316 ASN GLU VAL GLY VAL ALA ILE GLN GLU LYS LEU ARG GLU
SEQRES 6 A 316 GLN VAL VAL LYS ARG GLU GLU LEU PHE ILE VAL SER LYS
SEQRES 7 A 316 LEU TRP CYS THR TYR HIS GLU LYS GLY LEU VAL LYS GLY
SEQRES 8 A 316 ALA CYS GLN LYS THR LEU SER ASP LEU LYS LEU ASP TYR
SEQRES 9 A 316 LEU ASP LEU TYR LEU ILE HIS TRP PRO THR GLY PHE LYS
SEQRES 10 A 316 PRO GLY LYS GLU PHE PHE PRO LEU ASP GLU SER GLY ASN
SEQRES 11 A 316 VAL VAL PRO SER ASP THR ASN ILE LEU ASP THR TRP ALA
SEQRES 12 A 316 ALA MET GLU GLU LEU VAL ASP GLU GLY LEU VAL LYS ALA
SEQRES 13 A 316 ILE GLY ILE SER ASN PHE ASN HIS LEU GLN VAL GLU MET
SEQRES 14 A 316 ILE LEU ASN LYS PRO GLY LEU LYS TYR LYS PRO ALA VAL
SEQRES 15 A 316 ASN GLN ILE GLU CYS HIS PRO TYR LEU THR GLN GLU LYS
SEQRES 16 A 316 LEU ILE GLN TYR CYS GLN SER LYS GLY ILE VAL VAL THR
SEQRES 17 A 316 ALA TYR SER PRO LEU GLY SER PRO ASP ARG PRO TRP ALA
SEQRES 18 A 316 LYS PRO GLU ASP PRO SER LEU LEU GLU ASP PRO ARG ILE
SEQRES 19 A 316 LYS ALA ILE ALA ALA LYS HIS ASN LYS THR THR ALA GLN
SEQRES 20 A 316 VAL LEU ILE ARG PHE PRO MET GLN ARG ASN LEU VAL VAL
SEQRES 21 A 316 ILE PRO LYS SER VAL THR PRO GLU ARG ILE ALA GLU ASN
SEQRES 22 A 316 PHE LYS VAL PHE ASP PHE GLU LEU SER SER GLN ASP MET
SEQRES 23 A 316 THR THR LEU LEU SER TYR ASN ARG ASN TRP ARG VAL CYS
SEQRES 24 A 316 ALA LEU LEU SER CYS THR SER HIS LYS ASP TYR PRO PHE
SEQRES 25 A 316 HIS GLU GLU PHE
HET NAP A 318 48
HET CIT A 319 13
HET FIS A 320 20
HETNAM NAP NADP NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE
HETNAM CIT CITRIC ACID
HETNAM FIS (2S,4R)-2-AMINOFORMYL-6-FLUORO-SPIRO[CHROMAN-4,4'-
HETNAM 2 FIS IMIDAZOLIDINE]-2',5'-DIONE
HETSYN NAP 2'-MONOPHOSPHOADENOSINE 5'-DIPHOSPHORIBOSE
HETSYN FIS FIDARESTAT(STEREOISOMER)
FORMUL 2 NAP C21 H28 N7 O17 P3
FORMUL 3 CIT C6 H8 O7
FORMUL 4 FIS C12 H10 F N3 O4
FORMUL 5 HOH *684(H2 O)
HELIX 1 1 PRO A 23 GLY A 38 1 16
HELIX 2 2 ALA A 45 GLN A 49 5 5
HELIX 3 3 ASN A 50 GLU A 64 1 15
HELIX 4 4 LYS A 68 LEU A 72 5 5
HELIX 5 5 TRP A 79 HIS A 83 5 5
HELIX 6 6 LEU A 87 LYS A 100 1 14
HELIX 7 7 ASN A 136 GLU A 150 1 15
HELIX 8 8 ASN A 162 ASN A 171 1 10
HELIX 9 9 GLN A 192 LYS A 202 1 11
HELIX 10 10 SER A 226 GLU A 229 5 4
HELIX 11 11 ASP A 230 HIS A 240 1 11
HELIX 12 12 THR A 243 ARG A 255 1 13
HELIX 13 13 THR A 265 LYS A 274 1 10
HELIX 14 14 SER A 281 SER A 290 1 10
HELIX 15 15 LEU A 300 THR A 304 5 5
SHEET 1 A 2 ARG A 3 LEU A 5 0
SHEET 2 A 2 LYS A 11 PRO A 13 -1 O MET A 12 N ILE A 4
SHEET 1 B 8 LEU A 17 GLY A 18 0
SHEET 2 B 8 HIS A 41 ASP A 43 1 O ASP A 43 N LEU A 17
SHEET 3 B 8 PHE A 73 LEU A 78 1 O VAL A 75 N ILE A 42
SHEET 4 B 8 LEU A 106 ILE A 109 1 O LEU A 108 N LEU A 78
SHEET 5 B 8 ILE A 156 SER A 159 1 O GLY A 157 N ILE A 109
SHEET 6 B 8 VAL A 181 GLU A 185 1 O VAL A 181 N ILE A 158
SHEET 7 B 8 VAL A 205 TYR A 209 1 O THR A 207 N ILE A 184
SHEET 8 B 8 VAL A 258 VAL A 259 1 O VAL A 258 N ALA A 208
SITE 1 AC1 35 GLY A 18 THR A 19 TRP A 20 LYS A 21
SITE 2 AC1 35 ASP A 43 TYR A 48 HIS A 110 SER A 159
SITE 3 AC1 35 ASN A 160 GLN A 183 TYR A 209 SER A 210
SITE 4 AC1 35 PRO A 211 LEU A 212 GLY A 213 SER A 214
SITE 5 AC1 35 PRO A 215 ASP A 216 ALA A 245 ILE A 260
SITE 6 AC1 35 PRO A 261 LYS A 262 SER A 263 THR A 265
SITE 7 AC1 35 ARG A 268 GLU A 271 ASN A 272 HOH A1128
SITE 8 AC1 35 HOH A1129 HOH A1155 HOH A1248 HOH A1451
SITE 9 AC1 35 HOH A1491 HOH A1531 HOH A1553
SITE 1 AC2 13 TRP A 20 TYR A 48 TRP A 79 HIS A 110
SITE 2 AC2 13 TRP A 111 CYS A 298 HOH A1302 HOH A1361
SITE 3 AC2 13 HOH A1445 HOH A1449 HOH A1450 HOH A1451
SITE 4 AC2 13 HOH A1663
SITE 1 AC3 14 TRP A 20 LYS A 21 PRO A 218 HOH A1220
SITE 2 AC3 14 HOH A1266 HOH A1267 HOH A1297 HOH A1304
SITE 3 AC3 14 HOH A1386 HOH A1450 HOH A1547 HOH A1548
SITE 4 AC3 14 HOH A1549 HOH A1590
CRYST1 49.200 66.642 47.280 90.00 91.67 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 0.020325 0.000000 0.000593 0.00000
SCALE2 0.000000 0.015006 0.000000 0.00000
SCALE3 0.000000 0.000000 0.021160 0.00000
(ATOM LINES ARE NOT SHOWN.)
END
