HEADER TRANSFERASE/TRANSFERASE INHIBITOR 20-OCT-13 4N9B
TITLE FRAGMENT-BASED DESIGN OF 3-AMINOPYRIDINE-DERIVED AMIDES AS POTENT
TITLE 2 INHIBITORS OF HUMAN NICOTINAMIDE PHOSPHORIBOSYLTRANSFERASE (NAMPT)
COMPND MOL_ID: 1;
COMPND 2 MOLECULE: NICOTINAMIDE PHOSPHORIBOSYLTRANSFERASE;
COMPND 3 CHAIN: A, B;
COMPND 4 SYNONYM: NAMPRTASE, NAMPT, PRE-B-CELL COLONY-ENHANCING FACTOR 1, PRE-
COMPND 5 B CELL-ENHANCING FACTOR, VISFATIN;
COMPND 6 EC: 2.4.2.12;
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 GENE: NAMPT, PBEF, PBEF1;
SOURCE 6 EXPRESSION_SYSTEM: ESCHERICHIA COLI;
SOURCE 7 EXPRESSION_SYSTEM_TAXID: 562
KEYWDS TRANSFERASE-TRANSFERASE INHIBITOR COMPLEX
EXPDTA X-RAY DIFFRACTION
AUTHOR P.S.DRAGOVICH,G.ZHAO,T.BAUMEISTER,B.BRAVO,A.M.GIANNETTI,Y.HO,R.HUA,
AUTHOR 2 G.LI,X.LIANG,T.O'BRIEN,N.J.SKELTON,C.WANG,Q.ZHAI,A.OH,W.WANG,Y.WANG,
AUTHOR 3 Y.XIAO,P.YUEN,M.ZAK,X.ZHENG
REVDAT 3 20-SEP-23 4N9B 1 REMARK SEQADV
REVDAT 2 17-JUL-19 4N9B 1 REMARK
REVDAT 1 19-FEB-14 4N9B 0
JRNL AUTH P.S.DRAGOVICH,G.ZHAO,T.BAUMEISTER,B.BRAVO,A.M.GIANNETTI,
JRNL AUTH 2 Y.C.HO,R.HUA,G.LI,X.LIANG,X.MA,T.O'BRIEN,A.OH,N.J.SKELTON,
JRNL AUTH 3 C.WANG,W.WANG,Y.WANG,Y.XIAO,P.W.YUEN,M.ZAK,Q.ZHAO,X.ZHENG
JRNL TITL FRAGMENT-BASED DESIGN OF 3-AMINOPYRIDINE-DERIVED AMIDES AS
JRNL TITL 2 POTENT INHIBITORS OF HUMAN NICOTINAMIDE
JRNL TITL 3 PHOSPHORIBOSYLTRANSFERASE (NAMPT).
JRNL REF BIOORG.MED.CHEM.LETT. V. 24 954 2014
JRNL REFN ISSN 0960-894X
JRNL PMID 24433859
JRNL DOI 10.1016/J.BMCL.2013.12.062
REMARK 2
REMARK 2 RESOLUTION. 2.86 ANGSTROMS.
REMARK 3
REMARK 3 REFINEMENT.
REMARK 3 PROGRAM : PHENIX 1.7.3_928
REMARK 3 AUTHORS : PAUL ADAMS,PAVEL AFONINE,VINCENT CHEN,IAN
REMARK 3 : DAVIS,KRESHNA GOPAL,RALF GROSSE-KUNSTLEVE,
REMARK 3 : LI-WEI HUNG,ROBERT IMMORMINO,TOM IOERGER,
REMARK 3 : AIRLIE MCCOY,ERIK MCKEE,NIGEL MORIARTY,
REMARK 3 : REETAL PAI,RANDY READ,JANE RICHARDSON,
REMARK 3 : DAVID RICHARDSON,TOD ROMO,JIM SACCHETTINI,
REMARK 3 : NICHOLAS SAUTER,JACOB SMITH,LAURENT
REMARK 3 : STORONI,TOM TERWILLIGER,PETER ZWART
REMARK 3
REMARK 3 REFINEMENT TARGET : ML
REMARK 3
REMARK 3 DATA USED IN REFINEMENT.
REMARK 3 RESOLUTION RANGE HIGH (ANGSTROMS) : 2.86
REMARK 3 RESOLUTION RANGE LOW (ANGSTROMS) : 46.13
REMARK 3 MIN(FOBS/SIGMA_FOBS) : 0.000
REMARK 3 COMPLETENESS FOR RANGE (%) : 98.9
REMARK 3 NUMBER OF REFLECTIONS : 23903
REMARK 3
REMARK 3 FIT TO DATA USED IN REFINEMENT.
REMARK 3 R VALUE (WORKING + TEST SET) : 0.237
REMARK 3 R VALUE (WORKING SET) : 0.234
REMARK 3 FREE R VALUE : 0.284
REMARK 3 FREE R VALUE TEST SET SIZE (%) : 5.120
REMARK 3 FREE R VALUE TEST SET COUNT : 1224
REMARK 3
REMARK 3 FIT TO DATA USED IN REFINEMENT (IN BINS).
REMARK 3 BIN RESOLUTION RANGE COMPL. NWORK NFREE RWORK RFREE
REMARK 3 1 46.1318 - 5.9437 0.99 2574 142 0.2581 0.2867
REMARK 3 2 5.9437 - 4.7192 1.00 2575 128 0.2429 0.2655
REMARK 3 3 4.7192 - 4.1231 0.99 2544 138 0.2163 0.2690
REMARK 3 4 4.1231 - 3.7463 1.00 2530 122 0.2297 0.2779
REMARK 3 5 3.7463 - 3.4779 1.00 2528 145 0.2375 0.2907
REMARK 3 6 3.4779 - 3.2729 1.00 2533 130 0.2400 0.2912
REMARK 3 7 3.2729 - 3.1090 1.00 2557 132 0.2285 0.2976
REMARK 3 8 3.1090 - 2.9737 1.00 2506 144 0.2086 0.2914
REMARK 3 9 2.9737 - 2.8592 0.93 2332 143 0.2267 0.3174
REMARK 3
REMARK 3 BULK SOLVENT MODELLING.
REMARK 3 METHOD USED : FLAT BULK SOLVENT MODEL
REMARK 3 SOLVENT RADIUS : 1.10
REMARK 3 SHRINKAGE RADIUS : 0.86
REMARK 3 K_SOL : 0.32
REMARK 3 B_SOL : 0.00
REMARK 3
REMARK 3 ERROR ESTIMATES.
REMARK 3 COORDINATE ERROR (MAXIMUM-LIKELIHOOD BASED) : 0.400
REMARK 3 PHASE ERROR (DEGREES, MAXIMUM-LIKELIHOOD BASED) : 27.990
REMARK 3
REMARK 3 B VALUES.
REMARK 3 FROM WILSON PLOT (A**2) : NULL
REMARK 3 MEAN B VALUE (OVERALL, A**2) : NULL
REMARK 3 OVERALL ANISOTROPIC B VALUE.
REMARK 3 B11 (A**2) : 6.57670
REMARK 3 B22 (A**2) : 4.33110
REMARK 3 B33 (A**2) : 2.24270
REMARK 3 B12 (A**2) : 0.00000
REMARK 3 B13 (A**2) : 1.21290
REMARK 3 B23 (A**2) : 0.00000
REMARK 3
REMARK 3 TWINNING INFORMATION.
REMARK 3 FRACTION: NULL
REMARK 3 OPERATOR: NULL
REMARK 3
REMARK 3 DEVIATIONS FROM IDEAL VALUES.
REMARK 3 RMSD COUNT
REMARK 3 BOND : 0.002 7726
REMARK 3 ANGLE : 0.585 10466
REMARK 3 CHIRALITY : 0.041 1144
REMARK 3 PLANARITY : 0.003 1330
REMARK 3 DIHEDRAL : 11.097 2844
REMARK 3
REMARK 3 TLS DETAILS
REMARK 3 NUMBER OF TLS GROUPS : NULL
REMARK 3
REMARK 3 NCS DETAILS
REMARK 3 NUMBER OF NCS GROUPS : NULL
REMARK 3
REMARK 3 OTHER REFINEMENT REMARKS: HYDROGENS HAVE BEEN ADDED IN THE RIDING
REMARK 3 POSITIONS
REMARK 4
REMARK 4 4N9B COMPLIES WITH FORMAT V. 3.30, 13-JUL-11
REMARK 100
REMARK 100 THIS ENTRY HAS BEEN PROCESSED BY RCSB ON 22-OCT-13.
REMARK 100 THE DEPOSITION ID IS D_1000082914.
REMARK 200
REMARK 200 EXPERIMENTAL DETAILS
REMARK 200 EXPERIMENT TYPE : X-RAY DIFFRACTION
REMARK 200 DATE OF DATA COLLECTION : 05-APR-12
REMARK 200 TEMPERATURE (KELVIN) : 93
REMARK 200 PH : 8.6
REMARK 200 NUMBER OF CRYSTALS USED : 1
REMARK 200
REMARK 200 SYNCHROTRON (Y/N) : Y
REMARK 200 RADIATION SOURCE : SSRF
REMARK 200 BEAMLINE : BL17U
REMARK 200 X-RAY GENERATOR MODEL : NULL
REMARK 200 MONOCHROMATIC OR LAUE (M/L) : M
REMARK 200 WAVELENGTH OR RANGE (A) : 0.977408
REMARK 200 MONOCHROMATOR : DOUBLE CRYSTAL SI(111)
REMARK 200 OPTICS : NULL
REMARK 200
REMARK 200 DETECTOR TYPE : CCD
REMARK 200 DETECTOR MANUFACTURER : ADSC QUANTUM 315
REMARK 200 INTENSITY-INTEGRATION SOFTWARE : DENZO
REMARK 200 DATA SCALING SOFTWARE : SCALEPACK
REMARK 200
REMARK 200 NUMBER OF UNIQUE REFLECTIONS : 24001
REMARK 200 RESOLUTION RANGE HIGH (A) : 2.850
REMARK 200 RESOLUTION RANGE LOW (A) : 50.000
REMARK 200 REJECTION CRITERIA (SIGMA(I)) : 2.000
REMARK 200
REMARK 200 OVERALL.
REMARK 200 COMPLETENESS FOR RANGE (%) : 100.0
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) : 2.85
REMARK 200 HIGHEST RESOLUTION SHELL, RANGE LOW (A) : 2.95
REMARK 200 COMPLETENESS FOR SHELL (%) : 100.0
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: PHASER
REMARK 200 STARTING MODEL: PDB ENTRY 3DHF
REMARK 200
REMARK 200 REMARK: NULL
REMARK 280
REMARK 280 CRYSTAL
REMARK 280 SOLVENT CONTENT, VS (%): 47.05
REMARK 280 MATTHEWS COEFFICIENT, VM (ANGSTROMS**3/DA): 2.32
REMARK 280
REMARK 280 CRYSTALLIZATION CONDITIONS: CRYSTALS WERE GROWN FROM 0.2UL + 0.2UL
REMARK 280 DROPS CONTAINING 6MG/ML NAMPT, 0.1M SODIUM PHOSPHATE, 25-29%
REMARK 280 POLYETHYLENE GLYCOL 3350, 0.2M NACL, 1MM COMPOUND, PH 8.6, VAPOR
REMARK 280 DIFFUSION, HANGING DROP, TEMPERATURE 292K
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 53.15650
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: DIMERIC
REMARK 350 SOFTWARE DETERMINED QUATERNARY STRUCTURE: DIMERIC
REMARK 350 SOFTWARE USED: PISA
REMARK 350 TOTAL BURIED SURFACE AREA: 8900 ANGSTROM**2
REMARK 350 SURFACE AREA OF THE COMPLEX: 33070 ANGSTROM**2
REMARK 350 CHANGE IN SOLVENT FREE ENERGY: -56.0 KCAL/MOL
REMARK 350 APPLY THE FOLLOWING TO CHAINS: A, 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 1
REMARK 465 ASN A 2
REMARK 465 PRO A 3
REMARK 465 ALA A 4
REMARK 465 ALA A 5
REMARK 465 GLU A 6
REMARK 465 ALA A 7
REMARK 465 LYS A 43
REMARK 465 THR A 44
REMARK 465 GLU A 45
REMARK 465 ASN A 46
REMARK 465 SER A 47
REMARK 465 LYS A 48
REMARK 465 LEU A 49
REMARK 465 ARG A 50
REMARK 465 LYS A 51
REMARK 465 VAL A 52
REMARK 465 GLU A 487
REMARK 465 ALA A 488
REMARK 465 ALA A 489
REMARK 465 HIS A 490
REMARK 465 HIS A 491
REMARK 465 LEU A 492
REMARK 465 GLU A 493
REMARK 465 HIS A 494
REMARK 465 HIS A 495
REMARK 465 HIS A 496
REMARK 465 HIS A 497
REMARK 465 HIS A 498
REMARK 465 HIS A 499
REMARK 465 HIS A 500
REMARK 465 HIS A 501
REMARK 465 MET B 1
REMARK 465 ASN B 2
REMARK 465 PRO B 3
REMARK 465 ALA B 4
REMARK 465 ALA B 5
REMARK 465 GLU B 6
REMARK 465 ALA B 7
REMARK 465 LYS B 43
REMARK 465 THR B 44
REMARK 465 GLU B 45
REMARK 465 ASN B 46
REMARK 465 SER B 47
REMARK 465 LYS B 48
REMARK 465 LEU B 49
REMARK 465 ARG B 50
REMARK 465 LYS B 51
REMARK 465 VAL B 52
REMARK 465 GLU B 487
REMARK 465 ALA B 488
REMARK 465 ALA B 489
REMARK 465 HIS B 490
REMARK 465 HIS B 491
REMARK 465 LEU B 492
REMARK 465 GLU B 493
REMARK 465 HIS B 494
REMARK 465 HIS B 495
REMARK 465 HIS B 496
REMARK 465 HIS B 497
REMARK 465 HIS B 498
REMARK 465 HIS B 499
REMARK 465 HIS B 500
REMARK 465 HIS B 501
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 94 62.40 -113.62
REMARK 500 ASN A 97 71.57 -67.57
REMARK 500 CYS A 141 40.12 -108.95
REMARK 500 GLN A 154 -6.63 -58.71
REMARK 500 TYR A 231 -60.55 -130.82
REMARK 500 PHE A 269 62.71 -118.82
REMARK 500 TYR A 281 -56.87 -122.83
REMARK 500 GLU A 293 -59.97 -137.43
REMARK 500 ASP A 313 16.84 -151.65
REMARK 500 ASP A 416 79.50 -159.45
REMARK 500 TYR A 453 -166.34 -102.12
REMARK 500 ASP B 94 37.49 -98.88
REMARK 500 PHE B 96 119.45 -164.48
REMARK 500 CYS B 141 41.51 -101.57
REMARK 500 GLN B 154 -6.47 -58.31
REMARK 500 TYR B 231 -61.23 -127.90
REMARK 500 GLU B 293 -60.70 -135.58
REMARK 500 ASP B 313 14.10 -142.52
REMARK 500 ASP B 357 -166.47 -124.92
REMARK 500 ASP B 416 77.33 -152.01
REMARK 500 ASP B 420 89.01 -154.67
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 PO4 A 601
REMARK 800
REMARK 800 SITE_IDENTIFIER: AC2
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: BINDING SITE FOR RESIDUE 2HH A 602
REMARK 800
REMARK 800 SITE_IDENTIFIER: AC3
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: BINDING SITE FOR RESIDUE PO4 B 601
REMARK 800
REMARK 800 SITE_IDENTIFIER: AC4
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: BINDING SITE FOR RESIDUE 2HH B 602
REMARK 900
REMARK 900 RELATED ENTRIES
REMARK 900 RELATED ID: 4N9C RELATED DB: PDB
REMARK 900 RELATED ID: 4N9D RELATED DB: PDB
REMARK 900 RELATED ID: 4N9E RELATED DB: PDB
DBREF 4N9B A 1 491 UNP P43490 NAMPT_HUMAN 1 491
DBREF 4N9B B 1 491 UNP P43490 NAMPT_HUMAN 1 491
SEQADV 4N9B LEU A 492 UNP P43490 EXPRESSION TAG
SEQADV 4N9B GLU A 493 UNP P43490 EXPRESSION TAG
SEQADV 4N9B HIS A 494 UNP P43490 EXPRESSION TAG
SEQADV 4N9B HIS A 495 UNP P43490 EXPRESSION TAG
SEQADV 4N9B HIS A 496 UNP P43490 EXPRESSION TAG
SEQADV 4N9B HIS A 497 UNP P43490 EXPRESSION TAG
SEQADV 4N9B HIS A 498 UNP P43490 EXPRESSION TAG
SEQADV 4N9B HIS A 499 UNP P43490 EXPRESSION TAG
SEQADV 4N9B HIS A 500 UNP P43490 EXPRESSION TAG
SEQADV 4N9B HIS A 501 UNP P43490 EXPRESSION TAG
SEQADV 4N9B LEU B 492 UNP P43490 EXPRESSION TAG
SEQADV 4N9B GLU B 493 UNP P43490 EXPRESSION TAG
SEQADV 4N9B HIS B 494 UNP P43490 EXPRESSION TAG
SEQADV 4N9B HIS B 495 UNP P43490 EXPRESSION TAG
SEQADV 4N9B HIS B 496 UNP P43490 EXPRESSION TAG
SEQADV 4N9B HIS B 497 UNP P43490 EXPRESSION TAG
SEQADV 4N9B HIS B 498 UNP P43490 EXPRESSION TAG
SEQADV 4N9B HIS B 499 UNP P43490 EXPRESSION TAG
SEQADV 4N9B HIS B 500 UNP P43490 EXPRESSION TAG
SEQADV 4N9B HIS B 501 UNP P43490 EXPRESSION TAG
SEQRES 1 A 501 MET ASN PRO ALA ALA GLU ALA GLU PHE ASN ILE LEU LEU
SEQRES 2 A 501 ALA THR ASP SER TYR LYS VAL THR HIS TYR LYS GLN TYR
SEQRES 3 A 501 PRO PRO ASN THR SER LYS VAL TYR SER TYR PHE GLU CYS
SEQRES 4 A 501 ARG GLU LYS LYS THR GLU ASN SER LYS LEU ARG LYS VAL
SEQRES 5 A 501 LYS TYR GLU GLU THR VAL PHE TYR GLY LEU GLN TYR ILE
SEQRES 6 A 501 LEU ASN LYS TYR LEU LYS GLY LYS VAL VAL THR LYS GLU
SEQRES 7 A 501 LYS ILE GLN GLU ALA LYS ASP VAL TYR LYS GLU HIS PHE
SEQRES 8 A 501 GLN ASP ASP VAL PHE ASN GLU LYS GLY TRP ASN TYR ILE
SEQRES 9 A 501 LEU GLU LYS TYR ASP GLY HIS LEU PRO ILE GLU ILE LYS
SEQRES 10 A 501 ALA VAL PRO GLU GLY PHE VAL ILE PRO ARG GLY ASN VAL
SEQRES 11 A 501 LEU PHE THR VAL GLU ASN THR ASP PRO GLU CYS TYR TRP
SEQRES 12 A 501 LEU THR ASN TRP ILE GLU THR ILE LEU VAL GLN SER TRP
SEQRES 13 A 501 TYR PRO ILE THR VAL ALA THR ASN SER ARG GLU GLN LYS
SEQRES 14 A 501 LYS ILE LEU ALA LYS TYR LEU LEU GLU THR SER GLY ASN
SEQRES 15 A 501 LEU ASP GLY LEU GLU TYR LYS LEU HIS ASP PHE GLY TYR
SEQRES 16 A 501 ARG GLY VAL SER SER GLN GLU THR ALA GLY ILE GLY ALA
SEQRES 17 A 501 SER ALA HIS LEU VAL ASN PHE LYS GLY THR ASP THR VAL
SEQRES 18 A 501 ALA GLY LEU ALA LEU ILE LYS LYS TYR TYR GLY THR LYS
SEQRES 19 A 501 ASP PRO VAL PRO GLY TYR SER VAL PRO ALA ALA GLU HIS
SEQRES 20 A 501 SER THR ILE THR ALA TRP GLY LYS ASP HIS GLU LYS ASP
SEQRES 21 A 501 ALA PHE GLU HIS ILE VAL THR GLN PHE SER SER VAL PRO
SEQRES 22 A 501 VAL SER VAL VAL SER ASP SER TYR ASP ILE TYR ASN ALA
SEQRES 23 A 501 CYS GLU LYS ILE TRP GLY GLU ASP LEU ARG HIS LEU ILE
SEQRES 24 A 501 VAL SER ARG SER THR GLN ALA PRO LEU ILE ILE ARG PRO
SEQRES 25 A 501 ASP SER GLY ASN PRO LEU ASP THR VAL LEU LYS VAL LEU
SEQRES 26 A 501 GLU ILE LEU GLY LYS LYS PHE PRO VAL THR GLU ASN SER
SEQRES 27 A 501 LYS GLY TYR LYS LEU LEU PRO PRO TYR LEU ARG VAL ILE
SEQRES 28 A 501 GLN GLY ASP GLY VAL ASP ILE ASN THR LEU GLN GLU ILE
SEQRES 29 A 501 VAL GLU GLY MET LYS GLN LYS MET TRP SER ILE GLU ASN
SEQRES 30 A 501 ILE ALA PHE GLY SER GLY GLY GLY LEU LEU GLN LYS LEU
SEQRES 31 A 501 THR ARG ASP LEU LEU ASN CYS SER PHE LYS CYS SER TYR
SEQRES 32 A 501 VAL VAL THR ASN GLY LEU GLY ILE ASN VAL PHE LYS ASP
SEQRES 33 A 501 PRO VAL ALA ASP PRO ASN LYS ARG SER LYS LYS GLY ARG
SEQRES 34 A 501 LEU SER LEU HIS ARG THR PRO ALA GLY ASN PHE VAL THR
SEQRES 35 A 501 LEU GLU GLU GLY LYS GLY ASP LEU GLU GLU TYR GLY GLN
SEQRES 36 A 501 ASP LEU LEU HIS THR VAL PHE LYS ASN GLY LYS VAL THR
SEQRES 37 A 501 LYS SER TYR SER PHE ASP GLU ILE ARG LYS ASN ALA GLN
SEQRES 38 A 501 LEU ASN ILE GLU LEU GLU ALA ALA HIS HIS LEU GLU HIS
SEQRES 39 A 501 HIS HIS HIS HIS HIS HIS HIS
SEQRES 1 B 501 MET ASN PRO ALA ALA GLU ALA GLU PHE ASN ILE LEU LEU
SEQRES 2 B 501 ALA THR ASP SER TYR LYS VAL THR HIS TYR LYS GLN TYR
SEQRES 3 B 501 PRO PRO ASN THR SER LYS VAL TYR SER TYR PHE GLU CYS
SEQRES 4 B 501 ARG GLU LYS LYS THR GLU ASN SER LYS LEU ARG LYS VAL
SEQRES 5 B 501 LYS TYR GLU GLU THR VAL PHE TYR GLY LEU GLN TYR ILE
SEQRES 6 B 501 LEU ASN LYS TYR LEU LYS GLY LYS VAL VAL THR LYS GLU
SEQRES 7 B 501 LYS ILE GLN GLU ALA LYS ASP VAL TYR LYS GLU HIS PHE
SEQRES 8 B 501 GLN ASP ASP VAL PHE ASN GLU LYS GLY TRP ASN TYR ILE
SEQRES 9 B 501 LEU GLU LYS TYR ASP GLY HIS LEU PRO ILE GLU ILE LYS
SEQRES 10 B 501 ALA VAL PRO GLU GLY PHE VAL ILE PRO ARG GLY ASN VAL
SEQRES 11 B 501 LEU PHE THR VAL GLU ASN THR ASP PRO GLU CYS TYR TRP
SEQRES 12 B 501 LEU THR ASN TRP ILE GLU THR ILE LEU VAL GLN SER TRP
SEQRES 13 B 501 TYR PRO ILE THR VAL ALA THR ASN SER ARG GLU GLN LYS
SEQRES 14 B 501 LYS ILE LEU ALA LYS TYR LEU LEU GLU THR SER GLY ASN
SEQRES 15 B 501 LEU ASP GLY LEU GLU TYR LYS LEU HIS ASP PHE GLY TYR
SEQRES 16 B 501 ARG GLY VAL SER SER GLN GLU THR ALA GLY ILE GLY ALA
SEQRES 17 B 501 SER ALA HIS LEU VAL ASN PHE LYS GLY THR ASP THR VAL
SEQRES 18 B 501 ALA GLY LEU ALA LEU ILE LYS LYS TYR TYR GLY THR LYS
SEQRES 19 B 501 ASP PRO VAL PRO GLY TYR SER VAL PRO ALA ALA GLU HIS
SEQRES 20 B 501 SER THR ILE THR ALA TRP GLY LYS ASP HIS GLU LYS ASP
SEQRES 21 B 501 ALA PHE GLU HIS ILE VAL THR GLN PHE SER SER VAL PRO
SEQRES 22 B 501 VAL SER VAL VAL SER ASP SER TYR ASP ILE TYR ASN ALA
SEQRES 23 B 501 CYS GLU LYS ILE TRP GLY GLU ASP LEU ARG HIS LEU ILE
SEQRES 24 B 501 VAL SER ARG SER THR GLN ALA PRO LEU ILE ILE ARG PRO
SEQRES 25 B 501 ASP SER GLY ASN PRO LEU ASP THR VAL LEU LYS VAL LEU
SEQRES 26 B 501 GLU ILE LEU GLY LYS LYS PHE PRO VAL THR GLU ASN SER
SEQRES 27 B 501 LYS GLY TYR LYS LEU LEU PRO PRO TYR LEU ARG VAL ILE
SEQRES 28 B 501 GLN GLY ASP GLY VAL ASP ILE ASN THR LEU GLN GLU ILE
SEQRES 29 B 501 VAL GLU GLY MET LYS GLN LYS MET TRP SER ILE GLU ASN
SEQRES 30 B 501 ILE ALA PHE GLY SER GLY GLY GLY LEU LEU GLN LYS LEU
SEQRES 31 B 501 THR ARG ASP LEU LEU ASN CYS SER PHE LYS CYS SER TYR
SEQRES 32 B 501 VAL VAL THR ASN GLY LEU GLY ILE ASN VAL PHE LYS ASP
SEQRES 33 B 501 PRO VAL ALA ASP PRO ASN LYS ARG SER LYS LYS GLY ARG
SEQRES 34 B 501 LEU SER LEU HIS ARG THR PRO ALA GLY ASN PHE VAL THR
SEQRES 35 B 501 LEU GLU GLU GLY LYS GLY ASP LEU GLU GLU TYR GLY GLN
SEQRES 36 B 501 ASP LEU LEU HIS THR VAL PHE LYS ASN GLY LYS VAL THR
SEQRES 37 B 501 LYS SER TYR SER PHE ASP GLU ILE ARG LYS ASN ALA GLN
SEQRES 38 B 501 LEU ASN ILE GLU LEU GLU ALA ALA HIS HIS LEU GLU HIS
SEQRES 39 B 501 HIS HIS HIS HIS HIS HIS HIS
HET PO4 A 601 5
HET 2HH A 602 15
HET PO4 B 601 5
HET 2HH B 602 15
HETNAM PO4 PHOSPHATE ION
HETNAM 2HH 1-METHYL-N-(PYRIDIN-3-YL)-1H-PYRAZOLE-5-CARBOXAMIDE
FORMUL 3 PO4 2(O4 P 3-)
FORMUL 4 2HH 2(C10 H10 N4 O)
FORMUL 7 HOH *8(H2 O)
HELIX 1 1 ASN A 10 ALA A 14 5 5
HELIX 2 2 ASP A 16 GLN A 25 5 10
HELIX 3 3 GLY A 61 LEU A 70 1 10
HELIX 4 4 THR A 76 PHE A 91 1 16
HELIX 5 5 ASN A 97 TYR A 108 1 12
HELIX 6 6 ASP A 138 THR A 145 5 8
HELIX 7 7 ILE A 148 GLN A 154 1 7
HELIX 8 8 SER A 155 GLY A 181 1 27
HELIX 9 9 GLY A 185 TYR A 188 5 4
HELIX 10 10 SER A 200 LEU A 212 1 13
HELIX 11 11 VAL A 221 TYR A 231 1 11
HELIX 12 12 HIS A 247 ALA A 252 1 6
HELIX 13 13 HIS A 257 PHE A 269 1 13
HELIX 14 14 ASP A 282 LYS A 289 1 8
HELIX 15 15 LEU A 295 VAL A 300 1 6
HELIX 16 16 ASN A 316 LYS A 330 1 15
HELIX 17 17 ASP A 357 LYS A 371 1 15
HELIX 18 18 SER A 374 GLU A 376 5 3
HELIX 19 19 GLY A 383 GLN A 388 1 6
HELIX 20 20 ASP A 420 ARG A 424 5 5
HELIX 21 21 GLY A 446 GLU A 451 5 6
HELIX 22 22 SER A 472 ALA A 480 1 9
HELIX 23 23 ASN B 10 ALA B 14 5 5
HELIX 24 24 ASP B 16 GLN B 25 5 10
HELIX 25 25 GLY B 61 TYR B 69 1 9
HELIX 26 26 THR B 76 PHE B 91 1 16
HELIX 27 27 ASN B 97 TYR B 108 1 12
HELIX 28 28 ASP B 138 TYR B 142 5 5
HELIX 29 29 TRP B 143 ILE B 148 1 6
HELIX 30 30 ILE B 148 GLN B 154 1 7
HELIX 31 31 SER B 155 GLY B 181 1 27
HELIX 32 32 GLY B 185 TYR B 188 5 4
HELIX 33 33 SER B 200 LEU B 212 1 13
HELIX 34 34 VAL B 221 TYR B 231 1 11
HELIX 35 35 HIS B 247 ALA B 252 1 6
HELIX 36 36 HIS B 257 PHE B 269 1 13
HELIX 37 37 ASP B 282 LYS B 289 1 8
HELIX 38 38 LEU B 295 VAL B 300 1 6
HELIX 39 39 ASN B 316 LYS B 330 1 15
HELIX 40 40 ASP B 357 LYS B 371 1 15
HELIX 41 41 SER B 374 GLU B 376 5 3
HELIX 42 42 GLY B 383 GLN B 388 1 6
HELIX 43 43 ASP B 420 ARG B 424 5 5
HELIX 44 44 GLY B 446 GLU B 451 5 6
HELIX 45 45 SER B 472 ALA B 480 1 9
SHEET 1 A 7 LEU A 409 ASN A 412 0
SHEET 2 A 7 CYS A 397 THR A 406 -1 N VAL A 404 O ILE A 411
SHEET 3 A 7 THR A 30 CYS A 39 -1 N TYR A 34 O TYR A 403
SHEET 4 A 7 VAL A 130 ASN A 136 -1 O VAL A 134 N SER A 35
SHEET 5 A 7 ILE A 114 ALA A 118 -1 N LYS A 117 O THR A 133
SHEET 6 A 7 HIS A 459 LYS A 463 -1 O PHE A 462 N ILE A 116
SHEET 7 A 7 LYS A 466 VAL A 467 -1 O LYS A 466 N LYS A 463
SHEET 1 B 2 GLU A 56 VAL A 58 0
SHEET 2 B 2 VAL A 124 PRO A 126 -1 O ILE A 125 N THR A 57
SHEET 1 C 5 LEU A 190 ASP A 192 0
SHEET 2 C 5 ILE A 378 SER A 382 1 O PHE A 380 N HIS A 191
SHEET 3 C 5 LEU A 348 GLN A 352 1 N GLN A 352 O GLY A 381
SHEET 4 C 5 LEU A 308 ARG A 311 1 N LEU A 308 O ARG A 349
SHEET 5 C 5 VAL A 274 VAL A 277 1 N VAL A 274 O ILE A 309
SHEET 1 D 2 THR A 335 GLU A 336 0
SHEET 2 D 2 LYS A 342 LEU A 343 -1 O LEU A 343 N THR A 335
SHEET 1 E 2 SER A 431 ARG A 434 0
SHEET 2 E 2 PHE A 440 LEU A 443 -1 O LEU A 443 N SER A 431
SHEET 1 F 7 LEU B 409 ASN B 412 0
SHEET 2 F 7 CYS B 397 THR B 406 -1 N VAL B 404 O ILE B 411
SHEET 3 F 7 THR B 30 CYS B 39 -1 N TYR B 34 O TYR B 403
SHEET 4 F 7 VAL B 130 ASN B 136 -1 O VAL B 134 N SER B 35
SHEET 5 F 7 ILE B 114 ALA B 118 -1 N GLU B 115 O GLU B 135
SHEET 6 F 7 HIS B 459 LYS B 463 -1 O PHE B 462 N ILE B 116
SHEET 7 F 7 LYS B 466 VAL B 467 -1 O LYS B 466 N LYS B 463
SHEET 1 G 2 GLU B 56 VAL B 58 0
SHEET 2 G 2 VAL B 124 PRO B 126 -1 O ILE B 125 N THR B 57
SHEET 1 H 5 LEU B 190 ASP B 192 0
SHEET 2 H 5 ILE B 378 SER B 382 1 O PHE B 380 N HIS B 191
SHEET 3 H 5 LEU B 348 GLN B 352 1 N GLN B 352 O GLY B 381
SHEET 4 H 5 LEU B 308 ARG B 311 1 N ILE B 310 O ILE B 351
SHEET 5 H 5 VAL B 274 VAL B 277 1 N VAL B 274 O ILE B 309
SHEET 1 I 2 THR B 335 GLU B 336 0
SHEET 2 I 2 LYS B 342 LEU B 343 -1 O LEU B 343 N THR B 335
SHEET 1 J 2 SER B 431 ARG B 434 0
SHEET 2 J 2 PHE B 440 LEU B 443 -1 O LEU B 443 N SER B 431
SITE 1 AC1 3 ARG A 40 SER A 398 LYS A 400
SITE 1 AC2 10 PHE A 193 ARG A 196 ASP A 219 SER A 241
SITE 2 AC2 10 VAL A 242 ALA A 244 SER A 275 ARG A 311
SITE 3 AC2 10 ILE A 351 TYR B 18
SITE 1 AC3 5 ARG B 40 ARG B 392 SER B 398 LYS B 400
SITE 2 AC3 5 HOH B 703
SITE 1 AC4 10 TYR A 18 PHE B 193 ARG B 196 ASP B 219
SITE 2 AC4 10 SER B 241 VAL B 242 ALA B 244 SER B 275
SITE 3 AC4 10 ARG B 311 ILE B 351
CRYST1 60.132 106.313 83.264 90.00 96.27 90.00 P 1 21 1 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 0.016630 0.000000 0.001827 0.00000
SCALE2 0.000000 0.009406 0.000000 0.00000
SCALE3 0.000000 0.000000 0.012082 0.00000
(ATOM LINES ARE NOT SHOWN.)
END
