HEADER HYDROLASE 02-OCT-07 2ZA5
TITLE CRYSTAL STRUCTURE OF HUMAN TRYPTASE WITH POTENT NON-PEPTIDE INHIBITOR
COMPND MOL_ID: 1;
COMPND 2 MOLECULE: TRYPTASE BETA 2;
COMPND 3 CHAIN: A, B, C, D;
COMPND 4 FRAGMENT: UNP RESIDUES 31-275;
COMPND 5 EC: 3.4.21.59;
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: PICHIA PASTORIS;
SOURCE 6 EXPRESSION_SYSTEM_TAXID: 4922;
SOURCE 7 EXPRESSION_SYSTEM_VECTOR_TYPE: PLASMID
KEYWDS TRYPTASE, SERINE PROTEASE, TETRAMER, HYDROLASE
EXPDTA X-RAY DIFFRACTION
AUTHOR J.C.SPURLINO,S.A.BARNAKOV,F.LEWANDOWSKI,C.MILLIGAN
REVDAT 5 01-NOV-23 2ZA5 1 REMARK
REVDAT 4 11-OCT-17 2ZA5 1 REMARK
REVDAT 3 24-FEB-09 2ZA5 1 VERSN
REVDAT 2 01-APR-08 2ZA5 1 JRNL
REVDAT 1 26-FEB-08 2ZA5 0
JRNL AUTH M.J.COSTANZO,S.C.YABUT,H.-C.ZHANG,K.B.WHITE,L.DE GARAVILLA,
JRNL AUTH 2 Y.WANG,L.K.MINOR,B.A.TOUNGE,A.N.BARNAKOV,F.LEWANDOWSKI,
JRNL AUTH 3 C.MILLIGAN,J.C.SPURLINO,W.M.ABRAHAM,V.BOSWELL-SMITH,
JRNL AUTH 4 C.P.PAGE,B.E.MARYANOFF
JRNL TITL POTENT, NONPEPTIDE INHIBITORS OF HUMAN MAST CELL TRYPTASE.
JRNL TITL 2 SYNTHESIS AND BIOLOGICAL EVALUATION OF NOVEL SPIROCYCLIC
JRNL TITL 3 PIPERIDINE AMIDE DERIVATIVES
JRNL REF BIOORG.MED.CHEM.LETT. V. 18 2114 2008
JRNL REFN ISSN 0960-894X
JRNL PMID 18272363
JRNL DOI 10.1016/J.BMCL.2008.01.093
REMARK 1
REMARK 1 REFERENCE 1
REMARK 1 AUTH M.J.COSTANZO,S.C.YABUT,H.R.ALMOND,P.ANDRADE-GORDON,
REMARK 1 AUTH 2 T.W.CORCORAN,L.DE GARAVILLA,J.A.KAUFFMAN,W.M.ABRAHAM,
REMARK 1 AUTH 3 R.RECACHA,D.CHATTOPADHYAY,B.E.MARYANOFF
REMARK 1 TITL POTENT, SMALL-MOLECULE INHIBITORS OF HUMAN MAST CELL
REMARK 1 TITL 2 TRYPTASE. ANTIASTHMATIC ACTION OF A DIPEPTIDE-BASED
REMARK 1 TITL 3 TRANSITION-STATE ANALOGUE CONTAINING A BENZOTHIAZOLE KETONE
REMARK 1 REF J.MED.CHEM. V. 46 3865 2003
REMARK 1 REFN ISSN 0022-2623
REMARK 1 PMID 12930148
REMARK 1 DOI 10.1021/JM030050P
REMARK 2
REMARK 2 RESOLUTION. 2.30 ANGSTROMS.
REMARK 3
REMARK 3 REFINEMENT.
REMARK 3 PROGRAM : PHENIX
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 : NULL
REMARK 3
REMARK 3 DATA USED IN REFINEMENT.
REMARK 3 RESOLUTION RANGE HIGH (ANGSTROMS) : 2.30
REMARK 3 RESOLUTION RANGE LOW (ANGSTROMS) : 19.92
REMARK 3 MIN(FOBS/SIGMA_FOBS) : NULL
REMARK 3 COMPLETENESS FOR RANGE (%) : 97.9
REMARK 3 NUMBER OF REFLECTIONS : 50943
REMARK 3
REMARK 3 FIT TO DATA USED IN REFINEMENT.
REMARK 3 R VALUE (WORKING + TEST SET) : 0.184
REMARK 3 R VALUE (WORKING SET) : 0.181
REMARK 3 FREE R VALUE : 0.233
REMARK 3 FREE R VALUE TEST SET SIZE (%) : 4.980
REMARK 3 FREE R VALUE TEST SET COUNT : 2464
REMARK 3
REMARK 3 FIT TO DATA USED IN REFINEMENT (IN BINS).
REMARK 3 BIN RESOLUTION RANGE COMPL. NWORK NFREE RWORK RFREE
REMARK 3
REMARK 3 BULK SOLVENT MODELLING.
REMARK 3 METHOD USED : FLAT BULK SOLVENT MODEL
REMARK 3 SOLVENT RADIUS : NULL
REMARK 3 SHRINKAGE RADIUS : 0.90
REMARK 3 K_SOL : 0.39
REMARK 3 B_SOL : 27.68
REMARK 3
REMARK 3 ERROR ESTIMATES.
REMARK 3 COORDINATE ERROR (MAXIMUM-LIKELIHOOD BASED) : NULL
REMARK 3 PHASE ERROR (DEGREES, MAXIMUM-LIKELIHOOD BASED) : NULL
REMARK 3
REMARK 3 B VALUES.
REMARK 3 FROM WILSON PLOT (A**2) : NULL
REMARK 3 MEAN B VALUE (OVERALL, A**2) : 21.16
REMARK 3 OVERALL ANISOTROPIC B VALUE.
REMARK 3 B11 (A**2) : 0.40600
REMARK 3 B22 (A**2) : 0.40600
REMARK 3 B33 (A**2) : -0.81100
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 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 : 0.009 NULL
REMARK 3 ANGLE : 1.264 NULL
REMARK 3 CHIRALITY : 0.085 NULL
REMARK 3 PLANARITY : 0.009 NULL
REMARK 3 DIHEDRAL : 24.209 NULL
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: NULL
REMARK 4
REMARK 4 2ZA5 COMPLIES WITH FORMAT V. 3.30, 13-JUL-11
REMARK 100
REMARK 100 THIS ENTRY HAS BEEN PROCESSED BY PDBJ ON 04-OCT-07.
REMARK 100 THE DEPOSITION ID IS D_1000027713.
REMARK 200
REMARK 200 EXPERIMENTAL DETAILS
REMARK 200 EXPERIMENT TYPE : X-RAY DIFFRACTION
REMARK 200 DATE OF DATA COLLECTION : NULL
REMARK 200 TEMPERATURE (KELVIN) : 100
REMARK 200 PH : 6.1
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) : 1.00
REMARK 200 MONOCHROMATOR : NULL
REMARK 200 OPTICS : NULL
REMARK 200
REMARK 200 DETECTOR TYPE : CCD
REMARK 200 DETECTOR MANUFACTURER : ADSC QUANTUM 210
REMARK 200 INTENSITY-INTEGRATION SOFTWARE : DENZO, HKL-2000
REMARK 200 DATA SCALING SOFTWARE : SCALEPACK, HKL-2000
REMARK 200
REMARK 200 NUMBER OF UNIQUE REFLECTIONS : 51904
REMARK 200 RESOLUTION RANGE HIGH (A) : 2.300
REMARK 200 RESOLUTION RANGE LOW (A) : 20.000
REMARK 200 REJECTION CRITERIA (SIGMA(I)) : NULL
REMARK 200
REMARK 200 OVERALL.
REMARK 200 COMPLETENESS FOR RANGE (%) : NULL
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) : NULL
REMARK 200 HIGHEST RESOLUTION SHELL, RANGE LOW (A) : NULL
REMARK 200 COMPLETENESS FOR SHELL (%) : NULL
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: NULL
REMARK 200 STARTING MODEL: PDB ENTRY 1A0L
REMARK 200
REMARK 200 REMARK: NULL
REMARK 280
REMARK 280 CRYSTAL
REMARK 280 SOLVENT CONTENT, VS (%): 53.52
REMARK 280 MATTHEWS COEFFICIENT, VM (ANGSTROMS**3/DA): 2.65
REMARK 280
REMARK 280 CRYSTALLIZATION CONDITIONS: PH 6.1, VAPOR DIFFUSION, SITTING DROP
REMARK 290
REMARK 290 CRYSTALLOGRAPHIC SYMMETRY
REMARK 290 SYMMETRY OPERATORS FOR SPACE GROUP: P 41
REMARK 290
REMARK 290 SYMOP SYMMETRY
REMARK 290 NNNMMM OPERATOR
REMARK 290 1555 X,Y,Z
REMARK 290 2555 -X,-Y,Z+1/2
REMARK 290 3555 -Y,X,Z+1/4
REMARK 290 4555 Y,-X,Z+3/4
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 85.14200
REMARK 290 SMTRY1 3 0.000000 -1.000000 0.000000 0.00000
REMARK 290 SMTRY2 3 1.000000 0.000000 0.000000 0.00000
REMARK 290 SMTRY3 3 0.000000 0.000000 1.000000 42.57100
REMARK 290 SMTRY1 4 0.000000 1.000000 0.000000 0.00000
REMARK 290 SMTRY2 4 -1.000000 0.000000 0.000000 0.00000
REMARK 290 SMTRY3 4 0.000000 0.000000 1.000000 127.71300
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: TETRAMERIC
REMARK 350 SOFTWARE DETERMINED QUATERNARY STRUCTURE: TETRAMERIC
REMARK 350 SOFTWARE USED: PISA
REMARK 350 TOTAL BURIED SURFACE AREA: 9680 ANGSTROM**2
REMARK 350 SURFACE AREA OF THE COMPLEX: 38030 ANGSTROM**2
REMARK 350 CHANGE IN SOLVENT FREE ENERGY: -30.8 KCAL/MOL
REMARK 350 APPLY THE FOLLOWING TO CHAINS: A, B, C, D
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 LYS A 259
REMARK 465 PRO A 260
REMARK 465 LYS B 259
REMARK 465 PRO B 260
REMARK 465 LYS C 259
REMARK 465 PRO C 260
REMARK 465 LYS D 259
REMARK 465 PRO D 260
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 LYS A 258 CA C O CB CG CD CE
REMARK 470 LYS A 258 NZ
REMARK 470 LYS B 258 CA C O CB CG CD CE
REMARK 470 LYS B 258 NZ
REMARK 470 LYS C 258 CA C O CB CG CD CE
REMARK 470 LYS C 258 NZ
REMARK 470 GLY D 18 N
REMARK 470 LYS D 258 CA C O CB CG CD CE
REMARK 470 LYS D 258 NZ
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 50 141.15 -170.30
REMARK 500 ARG A 76 131.49 -38.53
REMARK 500 TYR A 81 -23.40 76.57
REMARK 500 TYR A 99 -14.13 -149.75
REMARK 500 SER A 119 -156.80 -125.26
REMARK 500 PHE A 134 70.19 45.33
REMARK 500 PRO A 136 151.95 -47.11
REMARK 500 SER A 228 -61.35 -123.75
REMARK 500 TRP A 229 -166.62 -162.67
REMARK 500 ARG B 76 115.61 -38.39
REMARK 500 TYR B 81 -27.89 83.33
REMARK 500 TYR B 99 -18.82 -144.05
REMARK 500 SER B 119 -154.48 -133.55
REMARK 500 SER B 228 -64.84 -121.85
REMARK 500 TRP B 229 -165.65 -161.92
REMARK 500 ARG C 76 127.56 -37.46
REMARK 500 TYR C 81 -26.24 75.05
REMARK 500 TYR C 99 -19.78 -147.57
REMARK 500 SER C 119 -145.85 -136.43
REMARK 500 PHE C 134 77.91 58.56
REMARK 500 ASN C 199 -153.25 -152.40
REMARK 500 SER C 228 -64.49 -123.84
REMARK 500 TYR D 81 -20.79 80.40
REMARK 500 TYR D 99 -22.08 -142.29
REMARK 500 SER D 119 -161.02 -120.17
REMARK 500 PRO D 157 30.64 -86.54
REMARK 500 ASN D 199 -158.08 -141.62
REMARK 500 SER D 209 132.92 -34.36
REMARK 500 SER D 228 -69.40 -121.10
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 2FF B 1
REMARK 800
REMARK 800 SITE_IDENTIFIER: AC2
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: BINDING SITE FOR RESIDUE 2FF A 4
REMARK 800
REMARK 800 SITE_IDENTIFIER: AC3
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: BINDING SITE FOR RESIDUE 2FF D 3
REMARK 800
REMARK 800 SITE_IDENTIFIER: AC4
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: BINDING SITE FOR RESIDUE 2FF C 2
DBREF 2ZA5 A 16 260 UNP Q6B052 Q6B052_HUMAN 31 275
DBREF 2ZA5 B 16 260 UNP Q6B052 Q6B052_HUMAN 31 275
DBREF 2ZA5 C 16 260 UNP Q6B052 Q6B052_HUMAN 31 275
DBREF 2ZA5 D 16 260 UNP Q6B052 Q6B052_HUMAN 31 275
SEQRES 1 A 245 ILE VAL GLY GLY GLN GLU ALA PRO ARG SER LYS TRP PRO
SEQRES 2 A 245 TRP GLN VAL SER LEU ARG VAL HIS GLY PRO TYR TRP MET
SEQRES 3 A 245 HIS PHE CYS GLY GLY SER LEU ILE HIS PRO GLN TRP VAL
SEQRES 4 A 245 LEU THR ALA ALA HIS CYS VAL GLY PRO ASP VAL LYS ASP
SEQRES 5 A 245 LEU ALA ALA LEU ARG VAL GLN LEU ARG GLU GLN HIS LEU
SEQRES 6 A 245 TYR TYR GLN ASP GLN LEU LEU PRO VAL SER ARG ILE ILE
SEQRES 7 A 245 VAL HIS PRO GLN PHE TYR THR ALA GLN ILE GLY ALA ASP
SEQRES 8 A 245 ILE ALA LEU LEU GLU LEU GLU GLU PRO VAL LYS VAL SER
SEQRES 9 A 245 SER HIS VAL HIS THR VAL THR LEU PRO PRO ALA SER GLU
SEQRES 10 A 245 THR PHE PRO PRO GLY MET PRO CYS TRP VAL THR GLY TRP
SEQRES 11 A 245 GLY ASP VAL ASP ASN ASP GLU ARG LEU PRO PRO PRO PHE
SEQRES 12 A 245 PRO LEU LYS GLN VAL LYS VAL PRO ILE MET GLU ASN HIS
SEQRES 13 A 245 ILE CYS ASP ALA LYS TYR HIS LEU GLY ALA TYR THR GLY
SEQRES 14 A 245 ASP ASP VAL ARG ILE VAL ARG ASP ASP MET LEU CYS ALA
SEQRES 15 A 245 GLY ASN THR ARG ARG ASP SER CYS GLN GLY ASP SER GLY
SEQRES 16 A 245 GLY PRO LEU VAL CYS LYS VAL ASN GLY THR TRP LEU GLN
SEQRES 17 A 245 ALA GLY VAL VAL SER TRP GLY GLU GLY CYS ALA GLN PRO
SEQRES 18 A 245 ASN ARG PRO GLY ILE TYR THR ARG VAL THR TYR TYR LEU
SEQRES 19 A 245 ASP TRP ILE HIS HIS TYR VAL PRO LYS LYS PRO
SEQRES 1 B 245 ILE VAL GLY GLY GLN GLU ALA PRO ARG SER LYS TRP PRO
SEQRES 2 B 245 TRP GLN VAL SER LEU ARG VAL HIS GLY PRO TYR TRP MET
SEQRES 3 B 245 HIS PHE CYS GLY GLY SER LEU ILE HIS PRO GLN TRP VAL
SEQRES 4 B 245 LEU THR ALA ALA HIS CYS VAL GLY PRO ASP VAL LYS ASP
SEQRES 5 B 245 LEU ALA ALA LEU ARG VAL GLN LEU ARG GLU GLN HIS LEU
SEQRES 6 B 245 TYR TYR GLN ASP GLN LEU LEU PRO VAL SER ARG ILE ILE
SEQRES 7 B 245 VAL HIS PRO GLN PHE TYR THR ALA GLN ILE GLY ALA ASP
SEQRES 8 B 245 ILE ALA LEU LEU GLU LEU GLU GLU PRO VAL LYS VAL SER
SEQRES 9 B 245 SER HIS VAL HIS THR VAL THR LEU PRO PRO ALA SER GLU
SEQRES 10 B 245 THR PHE PRO PRO GLY MET PRO CYS TRP VAL THR GLY TRP
SEQRES 11 B 245 GLY ASP VAL ASP ASN ASP GLU ARG LEU PRO PRO PRO PHE
SEQRES 12 B 245 PRO LEU LYS GLN VAL LYS VAL PRO ILE MET GLU ASN HIS
SEQRES 13 B 245 ILE CYS ASP ALA LYS TYR HIS LEU GLY ALA TYR THR GLY
SEQRES 14 B 245 ASP ASP VAL ARG ILE VAL ARG ASP ASP MET LEU CYS ALA
SEQRES 15 B 245 GLY ASN THR ARG ARG ASP SER CYS GLN GLY ASP SER GLY
SEQRES 16 B 245 GLY PRO LEU VAL CYS LYS VAL ASN GLY THR TRP LEU GLN
SEQRES 17 B 245 ALA GLY VAL VAL SER TRP GLY GLU GLY CYS ALA GLN PRO
SEQRES 18 B 245 ASN ARG PRO GLY ILE TYR THR ARG VAL THR TYR TYR LEU
SEQRES 19 B 245 ASP TRP ILE HIS HIS TYR VAL PRO LYS LYS PRO
SEQRES 1 C 245 ILE VAL GLY GLY GLN GLU ALA PRO ARG SER LYS TRP PRO
SEQRES 2 C 245 TRP GLN VAL SER LEU ARG VAL HIS GLY PRO TYR TRP MET
SEQRES 3 C 245 HIS PHE CYS GLY GLY SER LEU ILE HIS PRO GLN TRP VAL
SEQRES 4 C 245 LEU THR ALA ALA HIS CYS VAL GLY PRO ASP VAL LYS ASP
SEQRES 5 C 245 LEU ALA ALA LEU ARG VAL GLN LEU ARG GLU GLN HIS LEU
SEQRES 6 C 245 TYR TYR GLN ASP GLN LEU LEU PRO VAL SER ARG ILE ILE
SEQRES 7 C 245 VAL HIS PRO GLN PHE TYR THR ALA GLN ILE GLY ALA ASP
SEQRES 8 C 245 ILE ALA LEU LEU GLU LEU GLU GLU PRO VAL LYS VAL SER
SEQRES 9 C 245 SER HIS VAL HIS THR VAL THR LEU PRO PRO ALA SER GLU
SEQRES 10 C 245 THR PHE PRO PRO GLY MET PRO CYS TRP VAL THR GLY TRP
SEQRES 11 C 245 GLY ASP VAL ASP ASN ASP GLU ARG LEU PRO PRO PRO PHE
SEQRES 12 C 245 PRO LEU LYS GLN VAL LYS VAL PRO ILE MET GLU ASN HIS
SEQRES 13 C 245 ILE CYS ASP ALA LYS TYR HIS LEU GLY ALA TYR THR GLY
SEQRES 14 C 245 ASP ASP VAL ARG ILE VAL ARG ASP ASP MET LEU CYS ALA
SEQRES 15 C 245 GLY ASN THR ARG ARG ASP SER CYS GLN GLY ASP SER GLY
SEQRES 16 C 245 GLY PRO LEU VAL CYS LYS VAL ASN GLY THR TRP LEU GLN
SEQRES 17 C 245 ALA GLY VAL VAL SER TRP GLY GLU GLY CYS ALA GLN PRO
SEQRES 18 C 245 ASN ARG PRO GLY ILE TYR THR ARG VAL THR TYR TYR LEU
SEQRES 19 C 245 ASP TRP ILE HIS HIS TYR VAL PRO LYS LYS PRO
SEQRES 1 D 245 ILE VAL GLY GLY GLN GLU ALA PRO ARG SER LYS TRP PRO
SEQRES 2 D 245 TRP GLN VAL SER LEU ARG VAL HIS GLY PRO TYR TRP MET
SEQRES 3 D 245 HIS PHE CYS GLY GLY SER LEU ILE HIS PRO GLN TRP VAL
SEQRES 4 D 245 LEU THR ALA ALA HIS CYS VAL GLY PRO ASP VAL LYS ASP
SEQRES 5 D 245 LEU ALA ALA LEU ARG VAL GLN LEU ARG GLU GLN HIS LEU
SEQRES 6 D 245 TYR TYR GLN ASP GLN LEU LEU PRO VAL SER ARG ILE ILE
SEQRES 7 D 245 VAL HIS PRO GLN PHE TYR THR ALA GLN ILE GLY ALA ASP
SEQRES 8 D 245 ILE ALA LEU LEU GLU LEU GLU GLU PRO VAL LYS VAL SER
SEQRES 9 D 245 SER HIS VAL HIS THR VAL THR LEU PRO PRO ALA SER GLU
SEQRES 10 D 245 THR PHE PRO PRO GLY MET PRO CYS TRP VAL THR GLY TRP
SEQRES 11 D 245 GLY ASP VAL ASP ASN ASP GLU ARG LEU PRO PRO PRO PHE
SEQRES 12 D 245 PRO LEU LYS GLN VAL LYS VAL PRO ILE MET GLU ASN HIS
SEQRES 13 D 245 ILE CYS ASP ALA LYS TYR HIS LEU GLY ALA TYR THR GLY
SEQRES 14 D 245 ASP ASP VAL ARG ILE VAL ARG ASP ASP MET LEU CYS ALA
SEQRES 15 D 245 GLY ASN THR ARG ARG ASP SER CYS GLN GLY ASP SER GLY
SEQRES 16 D 245 GLY PRO LEU VAL CYS LYS VAL ASN GLY THR TRP LEU GLN
SEQRES 17 D 245 ALA GLY VAL VAL SER TRP GLY GLU GLY CYS ALA GLN PRO
SEQRES 18 D 245 ASN ARG PRO GLY ILE TYR THR ARG VAL THR TYR TYR LEU
SEQRES 19 D 245 ASP TRP ILE HIS HIS TYR VAL PRO LYS LYS PRO
HET 2FF A 4 31
HET 2FF B 1 31
HET 2FF C 2 31
HET 2FF D 3 31
HETNAM 2FF (5-(AMINOMETHYL)-2H-SPIRO[BENZOFURAN-3,4'-PIPERIDINE]-
HETNAM 2 2FF 1'-YL)(5-(PHENYLETHYNYL)FURAN-2-YL)METHANONE
FORMUL 5 2FF 4(C26 H24 N2 O3)
FORMUL 9 HOH *431(H2 O)
HELIX 1 1 ALA A 57 GLY A 62 1 6
HELIX 2 2 ASP A 67 ALA A 69 5 3
HELIX 3 3 GLU A 169 LEU A 179 1 11
HELIX 4 4 TYR A 248 VAL A 256 1 9
HELIX 5 5 ALA B 57 GLY B 62 1 6
HELIX 6 6 ASP B 67 ALA B 69 5 3
HELIX 7 7 GLU B 169 LEU B 179 1 11
HELIX 8 8 TYR B 248 VAL B 256 1 9
HELIX 9 9 ALA C 57 GLY C 62 1 6
HELIX 10 10 ASP C 67 ALA C 69 5 3
HELIX 11 11 GLU C 169 LEU C 179 1 11
HELIX 12 12 TYR C 248 HIS C 254 1 7
HELIX 13 13 ALA D 57 VAL D 61 5 5
HELIX 14 14 ASP D 67 ALA D 69 5 3
HELIX 15 15 GLU D 169 LEU D 179 1 11
HELIX 16 16 TYR D 248 VAL D 256 1 9
SHEET 1 A 8 GLN A 20 GLU A 21 0
SHEET 2 A 8 LYS A 161 LYS A 164 -1 O GLN A 162 N GLN A 20
SHEET 3 A 8 CYS A 140 GLY A 144 -1 N VAL A 142 O VAL A 163
SHEET 4 A 8 PRO A 212 VAL A 217 -1 O VAL A 214 N TRP A 141
SHEET 5 A 8 THR A 220 TRP A 229 -1 O THR A 220 N VAL A 217
SHEET 6 A 8 GLY A 240 ARG A 244 -1 O THR A 243 N VAL A 226
SHEET 7 A 8 MET A 194 ALA A 197 -1 N LEU A 195 O TYR A 242
SHEET 8 A 8 ILE A 167 MET A 168 -1 N MET A 168 O CYS A 196
SHEET 1 B 7 LEU A 86 LEU A 87 0
SHEET 2 B 7 LEU A 71 GLN A 74 -1 N VAL A 73 O LEU A 87
SHEET 3 B 7 GLN A 30 VAL A 35 -1 N SER A 32 O GLN A 74
SHEET 4 B 7 MET A 41 HIS A 50 -1 O CYS A 44 N LEU A 33
SHEET 5 B 7 TRP A 53 THR A 56 -1 O TRP A 53 N HIS A 50
SHEET 6 B 7 ALA A 108 LEU A 112 -1 O ALA A 108 N THR A 56
SHEET 7 B 7 VAL A 89 VAL A 94 -1 N ILE A 93 O LEU A 109
SHEET 1 C 8 GLN B 20 GLU B 21 0
SHEET 2 C 8 LYS B 161 LYS B 164 -1 O GLN B 162 N GLN B 20
SHEET 3 C 8 CYS B 140 GLY B 144 -1 N VAL B 142 O VAL B 163
SHEET 4 C 8 PRO B 212 VAL B 217 -1 O VAL B 214 N TRP B 141
SHEET 5 C 8 THR B 220 TRP B 229 -1 O THR B 220 N VAL B 217
SHEET 6 C 8 GLY B 240 ARG B 244 -1 O ILE B 241 N TRP B 229
SHEET 7 C 8 MET B 194 ALA B 197 -1 N LEU B 195 O TYR B 242
SHEET 8 C 8 ILE B 167 MET B 168 -1 N MET B 168 O CYS B 196
SHEET 1 D 6 LEU B 71 GLN B 74 0
SHEET 2 D 6 GLN B 30 VAL B 35 -1 N SER B 32 O GLN B 74
SHEET 3 D 6 MET B 41 HIS B 50 -1 O CYS B 44 N LEU B 33
SHEET 4 D 6 TRP B 53 THR B 56 -1 O LEU B 55 N SER B 47
SHEET 5 D 6 ALA B 108 LEU B 112 -1 O LEU B 110 N VAL B 54
SHEET 6 D 6 VAL B 89 VAL B 94 -1 N SER B 90 O GLU B 111
SHEET 1 E 8 GLN C 20 GLU C 21 0
SHEET 2 E 8 LYS C 161 VAL C 165 -1 O GLN C 162 N GLN C 20
SHEET 3 E 8 CYS C 140 GLY C 144 -1 N CYS C 140 O VAL C 165
SHEET 4 E 8 PRO C 212 VAL C 217 -1 O VAL C 214 N TRP C 141
SHEET 5 E 8 THR C 220 TRP C 229 -1 O LEU C 222 N CYS C 215
SHEET 6 E 8 GLY C 240 ARG C 244 -1 O ILE C 241 N TRP C 229
SHEET 7 E 8 MET C 194 ALA C 197 -1 N LEU C 195 O TYR C 242
SHEET 8 E 8 ILE C 167 MET C 168 -1 N MET C 168 O CYS C 196
SHEET 1 F 7 GLN C 30 VAL C 35 0
SHEET 2 F 7 MET C 41 HIS C 50 -1 O CYS C 44 N LEU C 33
SHEET 3 F 7 TRP C 53 THR C 56 -1 O LEU C 55 N SER C 47
SHEET 4 F 7 ALA C 108 LEU C 112 -1 O ALA C 108 N THR C 56
SHEET 5 F 7 LEU C 87 VAL C 94 -1 N ILE C 93 O LEU C 109
SHEET 6 F 7 LEU C 71 GLN C 74 -1 N VAL C 73 O LEU C 87
SHEET 7 F 7 GLN C 30 VAL C 35 -1 N ARG C 34 O ARG C 72
SHEET 1 G 8 GLN D 20 GLU D 21 0
SHEET 2 G 8 LYS D 161 LYS D 164 -1 O GLN D 162 N GLN D 20
SHEET 3 G 8 CYS D 140 GLY D 144 -1 N VAL D 142 O VAL D 163
SHEET 4 G 8 PRO D 212 VAL D 217 -1 O VAL D 214 N TRP D 141
SHEET 5 G 8 THR D 220 TRP D 229 -1 O THR D 220 N VAL D 217
SHEET 6 G 8 GLY D 240 ARG D 244 -1 O ILE D 241 N TRP D 229
SHEET 7 G 8 MET D 194 ALA D 197 -1 N LEU D 195 O TYR D 242
SHEET 8 G 8 ILE D 167 MET D 168 -1 N MET D 168 O CYS D 196
SHEET 1 H 7 GLN D 30 VAL D 35 0
SHEET 2 H 7 MET D 41 HIS D 50 -1 O CYS D 44 N LEU D 33
SHEET 3 H 7 TRP D 53 THR D 56 -1 O LEU D 55 N SER D 47
SHEET 4 H 7 ALA D 108 LEU D 112 -1 O LEU D 110 N VAL D 54
SHEET 5 H 7 LEU D 87 VAL D 94 -1 N ILE D 93 O LEU D 109
SHEET 6 H 7 LEU D 71 GLN D 74 -1 N VAL D 73 O LEU D 87
SHEET 7 H 7 GLN D 30 VAL D 35 -1 N SER D 32 O GLN D 74
SSBOND 1 CYS A 44 CYS A 60 1555 1555 2.06
SSBOND 2 CYS A 140 CYS A 215 1555 1555 2.03
SSBOND 3 CYS A 173 CYS A 196 1555 1555 2.05
SSBOND 4 CYS A 205 CYS A 233 1555 1555 2.05
SSBOND 5 CYS B 44 CYS B 60 1555 1555 2.06
SSBOND 6 CYS B 140 CYS B 215 1555 1555 2.03
SSBOND 7 CYS B 173 CYS B 196 1555 1555 2.03
SSBOND 8 CYS B 205 CYS B 233 1555 1555 2.06
SSBOND 9 CYS C 44 CYS C 60 1555 1555 2.06
SSBOND 10 CYS C 140 CYS C 215 1555 1555 2.02
SSBOND 11 CYS C 173 CYS C 196 1555 1555 2.05
SSBOND 12 CYS C 205 CYS C 233 1555 1555 2.05
SSBOND 13 CYS D 44 CYS D 60 1555 1555 2.08
SSBOND 14 CYS D 140 CYS D 215 1555 1555 2.04
SSBOND 15 CYS D 173 CYS D 196 1555 1555 2.04
SSBOND 16 CYS D 205 CYS D 233 1555 1555 2.05
CISPEP 1 GLY A 62 PRO A 63 0 7.71
CISPEP 2 PRO A 156 PRO A 157 0 2.34
CISPEP 3 GLY B 62 PRO B 63 0 5.17
CISPEP 4 PRO B 156 PRO B 157 0 4.96
CISPEP 5 GLY C 62 PRO C 63 0 5.12
CISPEP 6 PRO C 156 PRO C 157 0 1.41
CISPEP 7 GLY D 62 PRO D 63 0 6.40
CISPEP 8 PRO D 156 PRO D 157 0 0.75
SITE 1 AC1 15 GLN B 102 TYR B 177 ILE B 189 ASP B 203
SITE 2 AC1 15 SER B 204 CYS B 205 GLN B 206 SER B 209
SITE 3 AC1 15 TRP B 229 GLY B 230 GLU B 231 GLY B 232
SITE 4 AC1 15 HOH B 305 ASP D 64 TYR D 99
SITE 1 AC2 14 TYR A 177 ASP A 203 SER A 204 CYS A 205
SITE 2 AC2 14 GLN A 206 SER A 209 TRP A 229 GLY A 230
SITE 3 AC2 14 GLU A 231 GLY A 232 ARG A 238 GLY A 240
SITE 4 AC2 14 HOH A 272 ASP C 64
SITE 1 AC3 13 ASP B 64 TYR D 177 ILE D 189 ASP D 203
SITE 2 AC3 13 SER D 204 CYS D 205 GLN D 206 SER D 209
SITE 3 AC3 13 TRP D 229 GLY D 230 GLU D 231 GLY D 232
SITE 4 AC3 13 ARG D 238
SITE 1 AC4 16 ASP A 64 GLN C 102 TYR C 177 ILE C 189
SITE 2 AC4 16 ASP C 203 SER C 204 CYS C 205 GLN C 206
SITE 3 AC4 16 SER C 209 TRP C 229 GLY C 230 GLU C 231
SITE 4 AC4 16 GLY C 232 ARG C 238 HOH C 263 HOH C 285
CRYST1 82.678 82.678 170.284 90.00 90.00 90.00 P 41 16
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 0.012095 0.000000 0.000000 0.00000
SCALE2 0.000000 0.012095 0.000000 0.00000
SCALE3 0.000000 0.000000 0.005873 0.00000
(ATOM LINES ARE NOT SHOWN.)
END