HEADER OXIDOREDUCTASE 17-DEC-01 1KMV
TITLE HUMAN DIHYDROFOLATE REDUCTASE COMPLEXED WITH NADPH AND (Z)-6-(2-[2,5-
TITLE 2 DIMETHOXYPHENYL]ETHEN-1-YL)-2,4-DIAMINO-5-METHYLPYRIDO[2,3-
TITLE 3 D]PYRIMIDINE (SRI-9662), A LIPOPHILIC ANTIFOLATE
COMPND MOL_ID: 1;
COMPND 2 MOLECULE: DIHYDROFOLATE REDUCTASE;
COMPND 3 CHAIN: A;
COMPND 4 SYNONYM: DHFR;
COMPND 5 EC: 1.5.1.3;
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 EXPRESSION_SYSTEM: ESCHERICHIA COLI BL21(DE3);
SOURCE 6 EXPRESSION_SYSTEM_TAXID: 469008;
SOURCE 7 EXPRESSION_SYSTEM_STRAIN: BL21(DE3);
SOURCE 8 EXPRESSION_SYSTEM_CELLULAR_LOCATION: CYTOPLASM;
SOURCE 9 EXPRESSION_SYSTEM_VECTOR_TYPE: PLASMID;
SOURCE 10 EXPRESSION_SYSTEM_VECTOR: PET11A;
SOURCE 11 EXPRESSION_SYSTEM_PLASMID: PDFR
KEYWDS OXIDOREDUCTASE, ANTIPARASITIC DRUGS, REDUCTASE, LIPOPHILIC
KEYWDS 2 ANTIFOLATES
EXPDTA X-RAY DIFFRACTION
AUTHOR A.E.KLON,A.HEROUX,L.J.ROSS,V.PATHAK,C.A.JOHNSON,J.R.PIPER,D.W.BORHANI
REVDAT 5 03-APR-24 1KMV 1 REMARK
REVDAT 4 14-FEB-24 1KMV 1 REMARK
REVDAT 3 24-FEB-09 1KMV 1 VERSN
REVDAT 2 01-APR-03 1KMV 1 JRNL
REVDAT 1 10-JUL-02 1KMV 0
JRNL AUTH A.E.KLON,A.HEROUX,L.J.ROSS,V.PATHAK,C.A.JOHNSON,J.R.PIPER,
JRNL AUTH 2 D.W.BORHANI
JRNL TITL ATOMIC STRUCTURES OF HUMAN DIHYDROFOLATE REDUCTASE COMPLEXED
JRNL TITL 2 WITH NADPH AND TWO LIPOPHILIC ANTIFOLATES AT 1.09 A AND 1.05
JRNL TITL 3 A RESOLUTION.
JRNL REF J.MOL.BIOL. V. 320 677 2002
JRNL REFN ISSN 0022-2836
JRNL PMID 12096917
JRNL DOI 10.1016/S0022-2836(02)00469-2
REMARK 2
REMARK 2 RESOLUTION. 1.05 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) : 1.05
REMARK 3 RESOLUTION RANGE LOW (ANGSTROMS) : 20.00
REMARK 3 DATA CUTOFF (SIGMA(F)) : 0.000
REMARK 3 COMPLETENESS FOR RANGE (%) : 97.5
REMARK 3 CROSS-VALIDATION METHOD : THROUGHOUT
REMARK 3 FREE R VALUE TEST SET SELECTION : 5% OF THE REFLECTIONS WERE
REMARK 3 RANDOMLY SELECTED FOR THE
REMARK 3 TEST SET.
REMARK 3
REMARK 3 FIT TO DATA USED IN REFINEMENT (NO CUTOFF).
REMARK 3 R VALUE (WORKING + TEST SET, NO CUTOFF) : NULL
REMARK 3 R VALUE (WORKING SET, NO CUTOFF) : 0.130
REMARK 3 FREE R VALUE (NO CUTOFF) : 0.181
REMARK 3 FREE R VALUE TEST SET SIZE (%, NO CUTOFF) : 5.000
REMARK 3 FREE R VALUE TEST SET COUNT (NO CUTOFF) : 4325
REMARK 3 TOTAL NUMBER OF REFLECTIONS (NO CUTOFF) : 86271
REMARK 3
REMARK 3 FIT/AGREEMENT OF MODEL FOR DATA WITH F>4SIG(F).
REMARK 3 R VALUE (WORKING + TEST SET, F>4SIG(F)) : NULL
REMARK 3 R VALUE (WORKING SET, F>4SIG(F)) : 0.123
REMARK 3 FREE R VALUE (F>4SIG(F)) : 0.173
REMARK 3 FREE R VALUE TEST SET SIZE (%, F>4SIG(F)) : 5.000
REMARK 3 FREE R VALUE TEST SET COUNT (F>4SIG(F)) : 3436
REMARK 3 TOTAL NUMBER OF REFLECTIONS (F>4SIG(F)) : 68227
REMARK 3
REMARK 3 NUMBER OF NON-HYDROGEN ATOMS USED IN REFINEMENT.
REMARK 3 PROTEIN ATOMS : 1471
REMARK 3 NUCLEIC ACID ATOMS : 0
REMARK 3 HETEROGEN ATOMS : 82
REMARK 3 SOLVENT ATOMS : 338
REMARK 3
REMARK 3 MODEL REFINEMENT.
REMARK 3 OCCUPANCY SUM OF NON-HYDROGEN ATOMS : 1843.1
REMARK 3 OCCUPANCY SUM OF HYDROGEN ATOMS : 1412.0
REMARK 3 NUMBER OF DISCRETELY DISORDERED RESIDUES : 17
REMARK 3 NUMBER OF LEAST-SQUARES PARAMETERS : 17886
REMARK 3 NUMBER OF RESTRAINTS : 21912
REMARK 3
REMARK 3 RMS DEVIATIONS FROM RESTRAINT TARGET VALUES.
REMARK 3 BOND LENGTHS (A) : 0.017
REMARK 3 ANGLE DISTANCES (A) : 0.035
REMARK 3 SIMILAR DISTANCES (NO TARGET VALUES) (A) : 0.000
REMARK 3 DISTANCES FROM RESTRAINT PLANES (A) : 0.029
REMARK 3 ZERO CHIRAL VOLUMES (A**3) : 0.081
REMARK 3 NON-ZERO CHIRAL VOLUMES (A**3) : 0.086
REMARK 3 ANTI-BUMPING DISTANCE RESTRAINTS (A) : 0.031
REMARK 3 RIGID-BOND ADP COMPONENTS (A**2) : 0.006
REMARK 3 SIMILAR ADP COMPONENTS (A**2) : 0.058
REMARK 3 APPROXIMATELY ISOTROPIC ADPS (A**2) : 0.105
REMARK 3
REMARK 3 BULK SOLVENT MODELING.
REMARK 3 METHOD USED: MOEWS & KRETSINGER, J.MOL.BIOL.91(1973)201-228
REMARK 3
REMARK 3 STEREOCHEMISTRY TARGET VALUES : ENGH & HUBER
REMARK 3 SPECIAL CASE: NULL
REMARK 3
REMARK 3 OTHER REFINEMENT REMARKS: REFINEMENT BEGAN WITH RIGID-BODY
REMARK 3 MINIMIZATION (X-PLOR) USING THE COORDINATES AND
REMARK 3 ISOTROPIC TEMPERATURE FACTORS OF HDHFR AND NADPH FROM THE
REMARK 3 HDHFR/NADPH/SRI-9439 TERNARY COMPLEX (PDB ENTRY 1KMS),
REMARK 3 WITH THE CIS PEPTIDE BONDS RESTRAINED. ALTERNATING
REMARK 3 BETWEEN REFINEMENT IN X-PLOR AND MANUAL REBUILDING IN O
REMARK 3 RESULTED IN A FREE R-FACTOR OF 23.9%. SRI-9662 WAS ADDED
REMARK 3 AFTER ITS DENSITY BECAME APPARENT IN THE 2FO-FC AND FO-FC
REMARK 3 MAPS. REFINEMENT CONTINUED WITH THE ADDITION OF RIDING
REMARK 3 HYDROGEN ATOMS AND ANISOTROPIC TEMPERATURE FACTORS IN
REMARK 3 REFMAC AND ARP, RESULTING IN A FREE R-FACTOR OF 19.6%.
REMARK 3 MOST OF THE SIDE CHAINS WITH ALTERNATE CONFORMATIONS WERE
REMARK 3 MODELED AT THIS POINT. REFINEMENT WAS COMPLETED USING
REMARK 3 SHELXL. REFINEMENT OF THE ANISOTROPIC DISPLACEMENT
REMARK 3 PARAMETERS, ADDITION OF RIDING HYDROGENS, AND REMOVAL OF
REMARK 3 ALL RESTRAINTS ON THE PTERIDINE RING OF SRI-9662 RESULTED
REMARK 3 IN A FREE R-FACTOR OF 18.1%. SEVERAL LARGE PEAKS OF
REMARK 3 POSITIVE DIFFERENCE DENSITY WERE LOCATED IN THE NADPH
REMARK 3 BINDING SITE, THE LARGEST BEING 0.7 A AWAY FROM THE C7N
REMARK 3 CARBON ATOM, AND WERE ASSIGNED TO DMSO AT PARTIAL
REMARK 3 OCCUPANCY. HOH 607, 608, AND 609 ARE LOCATED IN THE
REMARK 3 NDP BINDING SITE, ARE PRESENT ONLY WHEN NDP IS NOT, AND ARE THUS
REMARK 3 INCLUDED IN
REMARK 3 ALTERNATE CONFORMATION B, ALONG WITH THE DMSO MOLECULE (NDP IS
REMARK 3 MODELED AS ALTERNATE CONFORMATION A).
REMARK 4
REMARK 4 1KMV COMPLIES WITH FORMAT V. 3.30, 13-JUL-11
REMARK 100
REMARK 100 THIS ENTRY HAS BEEN PROCESSED BY RCSB ON 07-JAN-02.
REMARK 100 THE DEPOSITION ID IS D_1000015122.
REMARK 200
REMARK 200 EXPERIMENTAL DETAILS
REMARK 200 EXPERIMENT TYPE : X-RAY DIFFRACTION
REMARK 200 DATE OF DATA COLLECTION : 18-JUN-98
REMARK 200 TEMPERATURE (KELVIN) : 100.0
REMARK 200 PH : 8.00
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) : 0.90
REMARK 200 MONOCHROMATOR : SI (111)
REMARK 200 OPTICS : PT-COATED MIRROR
REMARK 200
REMARK 200 DETECTOR TYPE : CCD
REMARK 200 DETECTOR MANUFACTURER : BRANDEIS - B4
REMARK 200 INTENSITY-INTEGRATION SOFTWARE : MOSFLM
REMARK 200 DATA SCALING SOFTWARE : CCP4 (SCALA)
REMARK 200
REMARK 200 NUMBER OF UNIQUE REFLECTIONS : 86349
REMARK 200 RESOLUTION RANGE HIGH (A) : 1.050
REMARK 200 RESOLUTION RANGE LOW (A) : 20.000
REMARK 200 REJECTION CRITERIA (SIGMA(I)) : 0.000
REMARK 200
REMARK 200 OVERALL.
REMARK 200 COMPLETENESS FOR RANGE (%) : 97.5
REMARK 200 DATA REDUNDANCY : 3.600
REMARK 200 R MERGE (I) : 0.05300
REMARK 200 R SYM (I) : 0.05300
REMARK 200 <I/SIGMA(I)> FOR THE DATA SET : 9.6000
REMARK 200
REMARK 200 IN THE HIGHEST RESOLUTION SHELL.
REMARK 200 HIGHEST RESOLUTION SHELL, RANGE HIGH (A) : 1.05
REMARK 200 HIGHEST RESOLUTION SHELL, RANGE LOW (A) : 1.09
REMARK 200 COMPLETENESS FOR SHELL (%) : 83.8
REMARK 200 DATA REDUNDANCY IN SHELL : 2.10
REMARK 200 R MERGE FOR SHELL (I) : 0.23100
REMARK 200 R SYM FOR SHELL (I) : 0.23100
REMARK 200 <I/SIGMA(I)> FOR SHELL : 2.800
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: UNPUBLISHED HUMAN DHFR STRUCTURE.
REMARK 200
REMARK 200 REMARK: NULL
REMARK 280
REMARK 280 CRYSTAL
REMARK 280 SOLVENT CONTENT, VS (%): 45.00
REMARK 280 MATTHEWS COEFFICIENT, VM (ANGSTROMS**3/DA): 2.20
REMARK 280
REMARK 280 CRYSTALLIZATION CONDITIONS: THE TERNARY COMPLEX OF DHFR WITH NADPH
REMARK 280 AND SRI-9662 WAS FORMED BY MIXING HUMAN DHFR (20 MG/ML IN 25 MM
REMARK 280 KPO4 (PH 7.0), 0.1 MM EDTA, AND 3 MM NAN3) WITH 60 MM NADPH,
REMARK 280 FOLLOWED 15 MINUTES LATER BY 60 MM OF INHIBITOR IN DMSO (FINAL
REMARK 280 CONCENTRATIONS OF 2 MM NADPH AND 2 MM INHIBITOR). THIS COMPLEX
REMARK 280 SOLUTION WAS MIXED WITH AN EQUAL VOLUME OF PRECIPITANT
REMARK 280 CONTAINING 24-33% PEG 4000, 0.2 M LI2SO4, 0.1 M TRIS CL (PH 7.9-
REMARK 280 8.4), 5% GLYCEROL, AND EQUILIBRATED WITH THE PRECIPITANT BY
REMARK 280 HANGING DROP VAPOR DIFFUSION AT 277 K. THE CRYSTAL GREW IN ABOUT
REMARK 280 3 WEEKS. THE CRYSTAL WAS FLASH-COOLED DIRECTLY IN LIQUID
REMARK 280 NITROGEN AFTER HARVESTING INTO MOTHER LIQUOR CONTAINING 10%
REMARK 280 GLYCEROL., PH 8.00, VAPOR DIFFUSION, HANGING DROP
REMARK 290
REMARK 290 CRYSTALLOGRAPHIC SYMMETRY
REMARK 290 SYMMETRY OPERATORS FOR SPACE GROUP: P 21 21 21
REMARK 290
REMARK 290 SYMOP SYMMETRY
REMARK 290 NNNMMM OPERATOR
REMARK 290 1555 X,Y,Z
REMARK 290 2555 -X+1/2,-Y,Z+1/2
REMARK 290 3555 -X,Y+1/2,-Z+1/2
REMARK 290 4555 X+1/2,-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 20.65000
REMARK 290 SMTRY2 2 0.000000 -1.000000 0.000000 0.00000
REMARK 290 SMTRY3 2 0.000000 0.000000 1.000000 41.34000
REMARK 290 SMTRY1 3 -1.000000 0.000000 0.000000 0.00000
REMARK 290 SMTRY2 3 0.000000 1.000000 0.000000 27.49500
REMARK 290 SMTRY3 3 0.000000 0.000000 -1.000000 41.34000
REMARK 290 SMTRY1 4 1.000000 0.000000 0.000000 20.65000
REMARK 290 SMTRY2 4 0.000000 -1.000000 0.000000 27.49500
REMARK 290 SMTRY3 4 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 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 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 ASP A 21 CG OD1 OD2
REMARK 470 LYS A 63 NZ
REMARK 470 LYS A 68 CE
REMARK 470 ARG A 77 CD NE NH1 NH2
REMARK 470 GLU A 78 CG CD OE1 OE2
REMARK 470 LYS A 98 NZ
REMARK 470 GLU A 101 CD OE1 OE2
REMARK 470 GLU A 123 CD OE1 OE2
REMARK 470 GLU A 143 CD OE1 OE2
REMARK 470 ASP A 186 CA C O CB CG OD1 OD2
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 28 NE - CZ - NH1 ANGL. DEV. = 6.9 DEGREES
REMARK 500 ARG A 28 NE - CZ - NH2 ANGL. DEV. = -3.8 DEGREES
REMARK 500 ARG A 32 NE - CZ - NH2 ANGL. DEV. = -3.7 DEGREES
REMARK 500 MET A 37 CG - SD - CE ANGL. DEV. = -11.3 DEGREES
REMARK 500 ARG A 65 NE - CZ - NH1 ANGL. DEV. = 3.2 DEGREES
REMARK 500 ASP A 95 CB - CG - OD2 ANGL. DEV. = 5.6 DEGREES
REMARK 500 ASP A 110 CB - CG - OD2 ANGL. DEV. = 5.5 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 110 -94.41 -100.68
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 SO4 A 204
REMARK 800
REMARK 800 SITE_IDENTIFIER: AC2
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: BINDING SITE FOR RESIDUE LII A 201
REMARK 800
REMARK 800 SITE_IDENTIFIER: AC3
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: BINDING SITE FOR RESIDUE NDP A 202
REMARK 800
REMARK 800 SITE_IDENTIFIER: AC4
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: BINDING SITE FOR RESIDUE DMS A 203
REMARK 900
REMARK 900 RELATED ENTRIES
REMARK 900 RELATED ID: 1KMS RELATED DB: PDB
REMARK 900 HUMAN DIHYDROFOLATE REDUCTASE COMPLEXED WITH NADPH AND 6- ([5-
REMARK 900 QUINOLYLAMINO]METHYL)-2,4-DIAMINO-5-METHYLPYRIDO[2,3- D]PYRIMIDINE
REMARK 900 (SRI-9439), A LIPOPHILIC ANTIFOLATE
DBREF 1KMV A 1 186 UNP P00374 DYR_HUMAN 1 186
SEQRES 1 A 186 VAL GLY SER LEU ASN CYS ILE VAL ALA VAL SER GLN ASN
SEQRES 2 A 186 MET GLY ILE GLY LYS ASN GLY ASP LEU PRO TRP PRO PRO
SEQRES 3 A 186 LEU ARG ASN GLU PHE ARG TYR PHE GLN ARG MET THR THR
SEQRES 4 A 186 THR SER SER VAL GLU GLY LYS GLN ASN LEU VAL ILE MET
SEQRES 5 A 186 GLY LYS LYS THR TRP PHE SER ILE PRO GLU LYS ASN ARG
SEQRES 6 A 186 PRO LEU LYS GLY ARG ILE ASN LEU VAL LEU SER ARG GLU
SEQRES 7 A 186 LEU LYS GLU PRO PRO GLN GLY ALA HIS PHE LEU SER ARG
SEQRES 8 A 186 SER LEU ASP ASP ALA LEU LYS LEU THR GLU GLN PRO GLU
SEQRES 9 A 186 LEU ALA ASN LYS VAL ASP MET VAL TRP ILE VAL GLY GLY
SEQRES 10 A 186 SER SER VAL TYR LYS GLU ALA MET ASN HIS PRO GLY HIS
SEQRES 11 A 186 LEU LYS LEU PHE VAL THR ARG ILE MET GLN ASP PHE GLU
SEQRES 12 A 186 SER ASP THR PHE PHE PRO GLU ILE ASP LEU GLU LYS TYR
SEQRES 13 A 186 LYS LEU LEU PRO GLU TYR PRO GLY VAL LEU SER ASP VAL
SEQRES 14 A 186 GLN GLU GLU LYS GLY ILE LYS TYR LYS PHE GLU VAL TYR
SEQRES 15 A 186 GLU LYS ASN ASP
HET SO4 A 204 5
HET LII A 201 25
HET NDP A 202 48
HET DMS A 203 4
HETNAM SO4 SULFATE ION
HETNAM LII (Z)-6-(2-[2,5-DIMETHOXYPHENYL]ETHEN-1-YL)-2,4-DIAMINO-
HETNAM 2 LII 5-METHYLPYRIDO[2,3-D]PYRIMIDINE
HETNAM NDP NADPH DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE
HETNAM 2 NDP PHOSPHATE
HETNAM DMS DIMETHYL SULFOXIDE
HETSYN LII SRI-9662
FORMUL 2 SO4 O4 S 2-
FORMUL 3 LII C18 H19 N5 O2
FORMUL 4 NDP C21 H30 N7 O17 P3
FORMUL 5 DMS C2 H6 O S
FORMUL 6 HOH *338(H2 O)
HELIX 1 1 LEU A 27 THR A 40 1 14
HELIX 2 2 LYS A 54 ILE A 60 1 7
HELIX 3 3 PRO A 61 ARG A 65 5 5
HELIX 4 4 SER A 92 GLN A 102 1 11
HELIX 5 5 GLY A 117 ASN A 126 1 10
SHEET 1 A 8 PHE A 88 SER A 90 0
SHEET 2 A 8 ILE A 71 LEU A 75 1 N VAL A 74 O PHE A 88
SHEET 3 A 8 GLN A 47 GLY A 53 1 N VAL A 50 O ILE A 71
SHEET 4 A 8 VAL A 109 ILE A 114 1 O TRP A 113 N LEU A 49
SHEET 5 A 8 LEU A 4 VAL A 10 1 N ASN A 5 O ILE A 114
SHEET 6 A 8 LEU A 131 ILE A 138 1 O PHE A 134 N CYS A 6
SHEET 7 A 8 ILE A 175 LYS A 184 -1 O TYR A 182 N LEU A 133
SHEET 8 A 8 LYS A 157 LEU A 158 -1 N LYS A 157 O GLU A 183
SHEET 1 B 8 PHE A 88 SER A 90 0
SHEET 2 B 8 ILE A 71 LEU A 75 1 N VAL A 74 O PHE A 88
SHEET 3 B 8 GLN A 47 GLY A 53 1 N VAL A 50 O ILE A 71
SHEET 4 B 8 VAL A 109 ILE A 114 1 O TRP A 113 N LEU A 49
SHEET 5 B 8 LEU A 4 VAL A 10 1 N ASN A 5 O ILE A 114
SHEET 6 B 8 LEU A 131 ILE A 138 1 O PHE A 134 N CYS A 6
SHEET 7 B 8 ILE A 175 LYS A 184 -1 O TYR A 182 N LEU A 133
SHEET 8 B 8 GLN A 170 GLU A 172 -1 N GLN A 170 O TYR A 177
SHEET 1 C 2 GLY A 15 GLY A 17 0
SHEET 2 C 2 THR A 146 PHE A 147 -1 N THR A 146 O GLY A 17
CISPEP 1 ARG A 65 PRO A 66 0 -9.10
CISPEP 2 GLY A 116 GLY A 117 0 6.07
SITE 1 AC1 5 ARG A 28 LYS A 68 GLY A 69 HOH A 370
SITE 2 AC1 5 HOH A 590
SITE 1 AC2 15 ILE A 7 VAL A 8 ALA A 9 GLU A 30
SITE 2 AC2 15 PHE A 31 PHE A 34 SER A 59 PRO A 61
SITE 3 AC2 15 VAL A 115 TYR A 121 NDP A 202 DMS A 203
SITE 4 AC2 15 HOH A 302 HOH A 441 HOH A 627
SITE 1 AC3 38 VAL A 8 ALA A 9 ILE A 16 GLY A 17
SITE 2 AC3 38 LYS A 18 GLY A 20 ASP A 21 LEU A 22
SITE 3 AC3 38 TRP A 24 GLY A 53 LYS A 54 LYS A 55
SITE 4 AC3 38 THR A 56 SER A 59 LEU A 75 SER A 76
SITE 5 AC3 38 ARG A 77 GLU A 78 ARG A 91 VAL A 115
SITE 6 AC3 38 GLY A 117 SER A 118 SER A 119 VAL A 120
SITE 7 AC3 38 TYR A 121 GLU A 123 THR A 146 LII A 201
SITE 8 AC3 38 HOH A 317 HOH A 339 HOH A 395 HOH A 549
SITE 9 AC3 38 HOH A 596 HOH A 603 HOH A 604 HOH A 607
SITE 10 AC3 38 HOH A 608 HOH A 609
SITE 1 AC4 7 VAL A 8 ALA A 9 ILE A 16 LEU A 22
SITE 2 AC4 7 VAL A 115 TYR A 121 LII A 201
CRYST1 41.300 54.990 82.680 90.00 90.00 90.00 P 21 21 21 4
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 0.024213 0.000000 0.000000 0.00000
SCALE2 0.000000 0.018185 0.000000 0.00000
SCALE3 0.000000 0.000000 0.012095 0.00000
(ATOM LINES ARE NOT SHOWN.)
END
