HEADER HYDROLASE/HYDROLASE INHIBITOR 17-AUG-11 3TGE
TITLE A NOVEL SERIES OF POTENT AND SELECTIVE PDE5 INHIBITOR1
COMPND MOL_ID: 1;
COMPND 2 MOLECULE: CGMP-SPECIFIC 3',5'-CYCLIC PHOSPHODIESTERASE;
COMPND 3 CHAIN: A;
COMPND 4 FRAGMENT: CATALYTIC DOMAIN RESIDUES 534-858;
COMPND 5 SYNONYM: CGMP-BINDING CGMP-SPECIFIC PHOSPHODIESTERASE, CGB-PDE;
COMPND 6 EC: 3.1.4.35;
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: PDE5A, PDE5;
SOURCE 6 EXPRESSION_SYSTEM: SPODOPTERA FRUGIPERDA;
SOURCE 7 EXPRESSION_SYSTEM_COMMON: FALL ARMYWORM;
SOURCE 8 EXPRESSION_SYSTEM_TAXID: 7108;
SOURCE 9 EXPRESSION_SYSTEM_CELL_LINE: SF9;
SOURCE 10 EXPRESSION_SYSTEM_VECTOR_TYPE: BACULOVIRUS
KEYWDS HYDROLASE-HYDROLASE INHIBITOR COMPLEX
EXPDTA X-RAY DIFFRACTION
AUTHOR S.HAN
REVDAT 3 28-FEB-24 3TGE 1 REMARK DBREF SEQADV LINK
REVDAT 2 16-AUG-17 3TGE 1 SOURCE REMARK
REVDAT 1 09-NOV-11 3TGE 0
JRNL AUTH R.O.HUGHES,T.MADDUX,D.JOSEPH ROGIER,S.LU,J.K.WALKER,
JRNL AUTH 2 E.JON JACOBSEN,J.M.RUMSEY,Y.ZHENG,A.MACINNES,B.R.BOND,S.HAN
JRNL TITL INVESTIGATION OF THE PYRAZINONES AS PDE5 INHIBITORS:
JRNL TITL 2 EVALUATION OF REGIOISOMERIC PROJECTIONS INTO THE SOLVENT
JRNL TITL 3 REGION.
JRNL REF BIOORG.MED.CHEM.LETT. V. 21 6348 2011
JRNL REFN ISSN 0960-894X
JRNL PMID 21955943
JRNL DOI 10.1016/J.BMCL.2011.08.106
REMARK 2
REMARK 2 RESOLUTION. 1.96 ANGSTROMS.
REMARK 3
REMARK 3 REFINEMENT.
REMARK 3 PROGRAM : BUSTER 2.11.1
REMARK 3 AUTHORS : BRICOGNE,BLANC,BRANDL,FLENSBURG,KELLER,
REMARK 3 : PACIOREK,ROVERSI,SHARFF,SMART,VONRHEIN,
REMARK 3 : WOMACK,MATTHEWS,TEN EYCK,TRONRUD
REMARK 3
REMARK 3 DATA USED IN REFINEMENT.
REMARK 3 RESOLUTION RANGE HIGH (ANGSTROMS) : 1.96
REMARK 3 RESOLUTION RANGE LOW (ANGSTROMS) : 19.33
REMARK 3 DATA CUTOFF (SIGMA(F)) : 0.000
REMARK 3 COMPLETENESS FOR RANGE (%) : 94.5
REMARK 3 NUMBER OF REFLECTIONS : 21674
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) : 0.180
REMARK 3 R VALUE (WORKING SET) : 0.179
REMARK 3 FREE R VALUE : 0.194
REMARK 3 FREE R VALUE TEST SET SIZE (%) : 5.120
REMARK 3 FREE R VALUE TEST SET COUNT : 1110
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 : 11
REMARK 3 BIN RESOLUTION RANGE HIGH (ANGSTROMS) : 1.96
REMARK 3 BIN RESOLUTION RANGE LOW (ANGSTROMS) : 2.06
REMARK 3 BIN COMPLETENESS (WORKING+TEST) (%) : 94.49
REMARK 3 REFLECTIONS IN BIN (WORKING + TEST SET) : 2755
REMARK 3 BIN R VALUE (WORKING + TEST SET) : 0.1836
REMARK 3 REFLECTIONS IN BIN (WORKING SET) : 2602
REMARK 3 BIN R VALUE (WORKING SET) : 0.1807
REMARK 3 BIN FREE R VALUE : 0.2323
REMARK 3 BIN FREE R VALUE TEST SET SIZE (%) : 5.55
REMARK 3 BIN FREE R VALUE TEST SET COUNT : 153
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 : 2619
REMARK 3 NUCLEIC ACID ATOMS : 0
REMARK 3 HETEROGEN ATOMS : 36
REMARK 3 SOLVENT ATOMS : 153
REMARK 3
REMARK 3 B VALUES.
REMARK 3 FROM WILSON PLOT (A**2) : 27.47
REMARK 3 MEAN B VALUE (OVERALL, A**2) : 28.16
REMARK 3 OVERALL ANISOTROPIC B VALUE.
REMARK 3 B11 (A**2) : 5.02910
REMARK 3 B22 (A**2) : 1.21490
REMARK 3 B33 (A**2) : -6.24400
REMARK 3 B12 (A**2) : 0.00000
REMARK 3 B13 (A**2) : -2.90270
REMARK 3 B23 (A**2) : 0.00000
REMARK 3
REMARK 3 ESTIMATED COORDINATE ERROR.
REMARK 3 ESD FROM LUZZATI PLOT (A) : 0.201
REMARK 3 DPI (BLOW EQ-10) BASED ON R VALUE (A) : 0.184
REMARK 3 DPI (BLOW EQ-9) BASED ON FREE R VALUE (A) : 0.138
REMARK 3 DPI (CRUICKSHANK) BASED ON R VALUE (A) : 0.186
REMARK 3 DPI (CRUICKSHANK) BASED ON FREE R VALUE (A) : 0.139
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 : 0.943
REMARK 3 CORRELATION COEFFICIENT FO-FC FREE : 0.942
REMARK 3
REMARK 3 NUMBER OF GEOMETRIC FUNCTION TERMS DEFINED : 15
REMARK 3 TERM COUNT WEIGHT FUNCTION.
REMARK 3 BOND LENGTHS : 2737 ; 2.000 ; HARMONIC
REMARK 3 BOND ANGLES : 3728 ; 2.000 ; HARMONIC
REMARK 3 TORSION ANGLES : 986 ; 2.000 ; SINUSOIDAL
REMARK 3 TRIGONAL CARBON PLANES : 80 ; 2.000 ; HARMONIC
REMARK 3 GENERAL PLANES : 409 ; 5.000 ; HARMONIC
REMARK 3 ISOTROPIC THERMAL FACTORS : 2737 ; 20.000 ; HARMONIC
REMARK 3 BAD NON-BONDED CONTACTS : 9 ; 5.000 ; SEMIHARMONIC
REMARK 3 IMPROPER TORSIONS : NULL ; NULL ; NULL
REMARK 3 PSEUDOROTATION ANGLES : NULL ; NULL ; NULL
REMARK 3 CHIRAL IMPROPER TORSION : 355 ; 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 : 3160 ; 4.000 ; SEMIHARMONIC
REMARK 3
REMARK 3 RMS DEVIATIONS FROM IDEAL VALUES.
REMARK 3 BOND LENGTHS (A) : 0.010
REMARK 3 BOND ANGLES (DEGREES) : 0.97
REMARK 3 PEPTIDE OMEGA TORSION ANGLES (DEGREES) : 2.81
REMARK 3 OTHER TORSION ANGLES (DEGREES) : 16.58
REMARK 3
REMARK 3 TLS DETAILS
REMARK 3 NUMBER OF TLS GROUPS : 1
REMARK 3
REMARK 3 TLS GROUP : 1
REMARK 3 SELECTION: CHAIN A
REMARK 3 ORIGIN FOR THE GROUP (A): 9.7242 -0.0660 19.9964
REMARK 3 T TENSOR
REMARK 3 T11: -0.0372 T22: -0.0502
REMARK 3 T33: -0.0658 T12: -0.0188
REMARK 3 T13: -0.0043 T23: -0.0048
REMARK 3 L TENSOR
REMARK 3 L11: 0.8265 L22: 0.8274
REMARK 3 L33: 0.7439 L12: -0.3002
REMARK 3 L13: -0.3514 L23: 0.3111
REMARK 3 S TENSOR
REMARK 3 S11: 0.0205 S12: 0.1116 S13: 0.0081
REMARK 3 S21: -0.0099 S22: -0.0111 S23: -0.0137
REMARK 3 S31: -0.0185 S32: -0.0564 S33: -0.0094
REMARK 3
REMARK 3 OTHER REFINEMENT REMARKS: NULL
REMARK 4
REMARK 4 3TGE COMPLIES WITH FORMAT V. 3.30, 13-JUL-11
REMARK 100
REMARK 100 THIS ENTRY HAS BEEN PROCESSED BY RCSB ON 25-AUG-11.
REMARK 100 THE DEPOSITION ID IS D_1000067449.
REMARK 200
REMARK 200 EXPERIMENTAL DETAILS
REMARK 200 EXPERIMENT TYPE : X-RAY DIFFRACTION
REMARK 200 DATE OF DATA COLLECTION : 20-NOV-05
REMARK 200 TEMPERATURE (KELVIN) : 100
REMARK 200 PH : 8.5
REMARK 200 NUMBER OF CRYSTALS USED : 1
REMARK 200
REMARK 200 SYNCHROTRON (Y/N) : Y
REMARK 200 RADIATION SOURCE : APS
REMARK 200 BEAMLINE : 17-ID
REMARK 200 X-RAY GENERATOR MODEL : NULL
REMARK 200 MONOCHROMATIC OR LAUE (M/L) : M
REMARK 200 WAVELENGTH OR RANGE (A) : 1.0
REMARK 200 MONOCHROMATOR : MIRRORS
REMARK 200 OPTICS : NULL
REMARK 200
REMARK 200 DETECTOR TYPE : CCD
REMARK 200 DETECTOR MANUFACTURER : ADSC QUANTUM 4
REMARK 200 INTENSITY-INTEGRATION SOFTWARE : HKL-2000
REMARK 200 DATA SCALING SOFTWARE : HKL-2000
REMARK 200
REMARK 200 NUMBER OF UNIQUE REFLECTIONS : 21675
REMARK 200 RESOLUTION RANGE HIGH (A) : 1.960
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 (%) : 94.7
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) : 1.96
REMARK 200 HIGHEST RESOLUTION SHELL, RANGE LOW (A) : 2.03
REMARK 200 COMPLETENESS FOR SHELL (%) : 99.1
REMARK 200 DATA REDUNDANCY IN SHELL : NULL
REMARK 200 R MERGE FOR SHELL (I) : 0.18500
REMARK 200 R SYM FOR SHELL (I) : NULL
REMARK 200 <I/SIGMA(I)> FOR SHELL : 5.400
REMARK 200
REMARK 200 DIFFRACTION PROTOCOL: SINGLE WAVELENGTH
REMARK 200 METHOD USED TO DETERMINE THE STRUCTURE: FOURIER SYNTHESIS
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 (%): 42.93
REMARK 280 MATTHEWS COEFFICIENT, VM (ANGSTROMS**3/DA): 2.16
REMARK 280
REMARK 280 CRYSTALLIZATION CONDITIONS: 0.2M MGSO4, 0.1M TRIS, 10-15% PEG3350,
REMARK 280 PH 8.5, EVAPORATION, TEMPERATURE 298K
REMARK 290
REMARK 290 CRYSTALLOGRAPHIC SYMMETRY
REMARK 290 SYMMETRY OPERATORS FOR SPACE GROUP: C 1 2 1
REMARK 290
REMARK 290 SYMOP SYMMETRY
REMARK 290 NNNMMM OPERATOR
REMARK 290 1555 X,Y,Z
REMARK 290 2555 -X,Y,-Z
REMARK 290 3555 X+1/2,Y+1/2,Z
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 0.00000
REMARK 290 SMTRY2 2 0.000000 1.000000 0.000000 0.00000
REMARK 290 SMTRY3 2 0.000000 0.000000 -1.000000 0.00000
REMARK 290 SMTRY1 3 1.000000 0.000000 0.000000 27.31500
REMARK 290 SMTRY2 3 0.000000 1.000000 0.000000 38.65550
REMARK 290 SMTRY3 3 0.000000 0.000000 1.000000 0.00000
REMARK 290 SMTRY1 4 -1.000000 0.000000 0.000000 27.31500
REMARK 290 SMTRY2 4 0.000000 1.000000 0.000000 38.65550
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 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 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 GLU A 534
REMARK 465 GLU A 535
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 630 -82.50 -78.47
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 MG A 865 MG
REMARK 620 N RES CSSEQI ATOM
REMARK 620 1 HOH A 30 O
REMARK 620 2 HOH A 47 O 83.9
REMARK 620 3 HOH A 83 O 90.2 81.9
REMARK 620 4 HOH A 533 O 105.8 102.0 163.9
REMARK 620 5 ASP A 654 OD1 87.5 166.8 88.0 90.0
REMARK 620 6 HOH A 859 O 153.2 69.9 80.9 85.8 117.0
REMARK 620 N 1 2 3 4 5
REMARK 620
REMARK 620 COORDINATION ANGLES FOR: M RES CSSEQI METAL
REMARK 620 ZN A 864 ZN
REMARK 620 N RES CSSEQI ATOM
REMARK 620 1 HOH A 533 O
REMARK 620 2 HIS A 617 NE2 146.3
REMARK 620 3 HIS A 653 NE2 103.8 109.8
REMARK 620 4 ASP A 654 OD2 86.7 91.4 90.0
REMARK 620 5 ASP A 764 OD1 92.7 88.9 90.5 179.3
REMARK 620 N 1 2 3 4
REMARK 800
REMARK 800 SITE
REMARK 800 SITE_IDENTIFIER: AC1
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: BINDING SITE FOR RESIDUE ZN A 864
REMARK 800
REMARK 800 SITE_IDENTIFIER: AC2
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: BINDING SITE FOR RESIDUE MG A 865
REMARK 800
REMARK 800 SITE_IDENTIFIER: AC3
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: BINDING SITE FOR RESIDUE TGE A 999
REMARK 900
REMARK 900 RELATED ENTRIES
REMARK 900 RELATED ID: 3TGG RELATED DB: PDB
REMARK 999
REMARK 999 SEQUENCE
REMARK 999 PDE5 LOOP SWAPPED RESIDUES 657-682 TAKEN FROM PDE5 AND INSERTED
REMARK 999 INTO THE EQUIVALENT REGION OF PDE5.
DBREF 3TGE A 534 656 UNP O76074 PDE5A_HUMAN 534 656
DBREF 3TGE A 657 681A PDB 3TGE 3TGE 657 681
DBREF 3TGE A 682 858 UNP O76074 PDE5A_HUMAN 682 858
SEQADV 3TGE GLU A 751 UNP O76074 GLN 751 CONFLICT
SEQRES 1 A 326 GLU GLU GLU THR ARG GLU LEU GLN SER LEU ALA ALA ALA
SEQRES 2 A 326 VAL VAL PRO SER ALA GLN THR LEU LYS ILE THR ASP PHE
SEQRES 3 A 326 SER PHE SER ASP PHE GLU LEU SER ASP LEU GLU THR ALA
SEQRES 4 A 326 LEU CYS THR ILE ARG MET PHE THR ASP LEU ASN LEU VAL
SEQRES 5 A 326 GLN ASN PHE GLN MET LYS HIS GLU VAL LEU CYS ARG TRP
SEQRES 6 A 326 ILE LEU SER VAL LYS LYS ASN TYR ARG LYS ASN VAL ALA
SEQRES 7 A 326 TYR HIS ASN TRP ARG HIS ALA PHE ASN THR ALA GLN CYS
SEQRES 8 A 326 MET PHE ALA ALA LEU LYS ALA GLY LYS ILE GLN ASN LYS
SEQRES 9 A 326 LEU THR ASP LEU GLU ILE LEU ALA LEU LEU ILE ALA ALA
SEQRES 10 A 326 LEU SER HIS ASP LEU ASP HIS PRO GLY VAL SER ASN GLN
SEQRES 11 A 326 PHE LEU ILE ASN THR ASN SER GLU LEU ALA LEU MET TYR
SEQRES 12 A 326 ASN ASP GLU SER VAL LEU GLU HIS HIS HIS PHE ASP GLN
SEQRES 13 A 326 CYS LEU MET ILE LEU ASN SER PRO GLY ASN GLN ILE LEU
SEQRES 14 A 326 SER GLY LEU SER ILE GLU GLU TYR LYS THR THR LEU LYS
SEQRES 15 A 326 ILE ILE LYS GLN ALA ILE LEU ALA THR ASP LEU ALA LEU
SEQRES 16 A 326 TYR ILE LYS ARG ARG GLY GLU PHE PHE GLU LEU ILE ARG
SEQRES 17 A 326 LYS ASN GLN PHE ASN LEU GLU ASP PRO HIS GLU LYS GLU
SEQRES 18 A 326 LEU PHE LEU ALA MET LEU MET THR ALA CYS ASP LEU SER
SEQRES 19 A 326 ALA ILE THR LYS PRO TRP PRO ILE GLN GLN ARG ILE ALA
SEQRES 20 A 326 GLU LEU VAL ALA THR GLU PHE PHE ASP GLN GLY ASP ARG
SEQRES 21 A 326 GLU ARG LYS GLU LEU ASN ILE GLU PRO THR ASP LEU MET
SEQRES 22 A 326 ASN ARG GLU LYS LYS ASN LYS ILE PRO SER MET GLN VAL
SEQRES 23 A 326 GLY PHE ILE ASP ALA ILE CYS LEU GLN LEU TYR GLU ALA
SEQRES 24 A 326 LEU THR HIS VAL SER GLU ASP CYS PHE PRO LEU LEU ASP
SEQRES 25 A 326 GLY CYS ARG LYS ASN ARG GLN LYS TRP GLN ALA LEU ALA
SEQRES 26 A 326 GLU
HET ZN A 864 1
HET MG A 865 1
HET TGE A 999 66
HETNAM ZN ZINC ION
HETNAM MG MAGNESIUM ION
HETNAM TGE 7-(6-METHOXYPYRIDIN-3-YL)-3-{[2-(MORPHOLIN-4-YL)
HETNAM 2 TGE ETHYL]AMINO}-1-(2-PROPOXYETHYL)PYRIDO[3,4-B]PYRAZIN-
HETNAM 3 TGE 2(1H)-ONE
FORMUL 2 ZN ZN 2+
FORMUL 3 MG MG 2+
FORMUL 4 TGE C24 H32 N6 O4
FORMUL 5 HOH *153(H2 O)
HELIX 1 1 GLU A 536 ALA A 546 1 11
HELIX 2 2 SER A 550 LYS A 555 1 6
HELIX 3 3 SER A 567 LEU A 582 1 16
HELIX 4 4 ASN A 583 PHE A 588 1 6
HELIX 5 5 LYS A 591 ASN A 605 1 15
HELIX 6 6 ASN A 614 ALA A 631 1 18
HELIX 7 7 ILE A 634 LEU A 638 5 5
HELIX 8 8 THR A 639 HIS A 653 1 15
HELIX 9 9 SER A 661 THR A 668 1 8
HELIX 10 10 SER A 670 TYR A 676 1 7
HELIX 11 11 SER A 680 SER A 695 1 17
HELIX 12 12 SER A 705 ALA A 722 1 18
HELIX 13 13 ASP A 724 LYS A 741 1 18
HELIX 14 14 ASP A 748 LEU A 765 1 18
HELIX 15 15 SER A 766 LYS A 770 5 5
HELIX 16 16 PRO A 771 ASN A 798 1 28
HELIX 17 17 THR A 802 ASN A 811 5 10
HELIX 18 18 LYS A 812 ILE A 824 1 13
HELIX 19 19 CYS A 825 SER A 836 1 12
HELIX 20 20 CYS A 839 GLU A 858 1 20
LINK O HOH A 30 MG MG A 865 1555 1555 2.11
LINK O HOH A 47 MG MG A 865 1555 1555 2.03
LINK O HOH A 83 MG MG A 865 1555 1555 2.24
LINK O HOH A 533 ZN ZN A 864 1555 1555 1.94
LINK O HOH A 533 MG MG A 865 1555 1555 2.19
LINK NE2 HIS A 617 ZN ZN A 864 1555 1555 1.99
LINK NE2 HIS A 653 ZN ZN A 864 1555 1555 1.98
LINK OD2 ASP A 654 ZN ZN A 864 1555 1555 2.14
LINK OD1 ASP A 654 MG MG A 865 1555 1555 1.94
LINK OD1 ASP A 764 ZN ZN A 864 1555 1555 2.22
LINK O HOH A 859 MG MG A 865 1555 1555 2.34
SITE 1 AC1 5 HOH A 533 HIS A 617 HIS A 653 ASP A 654
SITE 2 AC1 5 ASP A 764
SITE 1 AC2 6 HOH A 30 HOH A 47 HOH A 83 HOH A 533
SITE 2 AC2 6 ASP A 654 HOH A 859
SITE 1 AC3 12 HOH A 525 ALA A 545 ILE A 729 ALA A 767
SITE 2 AC3 12 ILE A 768 GLN A 775 ALA A 779 LEU A 804
SITE 3 AC3 12 MET A 816 GLN A 817 PHE A 820 HOH A 888
CRYST1 54.630 77.311 78.265 90.00 101.19 90.00 C 1 2 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 0.018305 0.000000 0.003621 0.00000
SCALE2 0.000000 0.012935 0.000000 0.00000
SCALE3 0.000000 0.000000 0.013025 0.00000
(ATOM LINES ARE NOT SHOWN.)
END
