HEADER HYDROLASE/HYDROLASE INHIBITOR 02-OCT-05 2C2Z
TITLE CRYSTAL STRUCTURE OF CASPASE-8 IN COMPLEX WITH AZA-PEPTIDE MICHAEL
TITLE 2 ACCEPTOR INHIBITOR
COMPND MOL_ID: 1;
COMPND 2 MOLECULE: CASPASE-8 P18 SUBUNIT;
COMPND 3 CHAIN: A;
COMPND 4 FRAGMENT: ALPHA SUB-UNIT, RESIDUES 218-374;
COMPND 5 EC: 3.4.22.-;
COMPND 6 ENGINEERED: YES;
COMPND 7 MOL_ID: 2;
COMPND 8 MOLECULE: CASPASE-8 P10 SUBUNIT;
COMPND 9 CHAIN: B;
COMPND 10 FRAGMENT: BETA-SUBUNIT, RESIDUES 376-479;
COMPND 11 EC: 3.4.22.-;
COMPND 12 ENGINEERED: YES;
COMPND 13 MOL_ID: 3;
COMPND 14 MOLECULE: AZA-PEPTIDE INHIBITOR (5S, 8R, 11S)-8-(2-CARBOXYETHYL)
COMPND 15 -14-[4-(3,4-DIHYDROQUINOLIN-1(2H)-YL)-4-OXOBUTANOYL]
COMPND 16 -11-[(1R)-1-HYDROXYETHYL]-5-(2-METHYLPROPYL)-3,6,9,12-TETRAOXO
COMPND 17 -1-PHENYL-2-OXA-4,7,10,13,14-PENTAAZAHEXADECAN-16-OIC ACID;
COMPND 18 CHAIN: C;
COMPND 19 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;
SOURCE 6 EXPRESSION_SYSTEM_TAXID: 469008;
SOURCE 7 EXPRESSION_SYSTEM_STRAIN: BL21(DE3);
SOURCE 8 EXPRESSION_SYSTEM_VECTOR_TYPE: PLASMID;
SOURCE 9 EXPRESSION_SYSTEM_PLASMID: PET11D;
SOURCE 10 MOL_ID: 2;
SOURCE 11 ORGANISM_SCIENTIFIC: HOMO SAPIENS;
SOURCE 12 ORGANISM_COMMON: HUMAN;
SOURCE 13 ORGANISM_TAXID: 9606;
SOURCE 14 EXPRESSION_SYSTEM: ESCHERICHIA COLI;
SOURCE 15 EXPRESSION_SYSTEM_TAXID: 469008;
SOURCE 16 EXPRESSION_SYSTEM_STRAIN: BL21(DE3);
SOURCE 17 EXPRESSION_SYSTEM_VECTOR_TYPE: PLASMID;
SOURCE 18 EXPRESSION_SYSTEM_PLASMID: PET11D;
SOURCE 19 MOL_ID: 3;
SOURCE 20 SYNTHETIC: YES;
SOURCE 21 ORGANISM_SCIENTIFIC: SYNTHETIC CONSTRUCT;
SOURCE 22 ORGANISM_TAXID: 32630
KEYWDS HYDROLASE-HYDROLASE INHIBITOR COMPLEX, APOPTOSIS, CYSTEINE-PROTEASE,
KEYWDS 2 ICE, THIOL PROTEASE, ZYMOGEN, CPP32, YAMA, AZA-PEPTIDE, MICHAEL
KEYWDS 3 ACCEPTOR, AZA-ASP, CLAN CD
EXPDTA X-RAY DIFFRACTION
AUTHOR R.GANESAN,S.JELAKOVIC,O.D.EKICI,Z.Z.LI,K.E.JAMES,J.L.ASGIAN,
AUTHOR 2 A.J.CAMPBELL,J.MIKOLAJCZYK,G.S.SALVESEN,J.C.POWERS,M.G.GRUETTER
REVDAT 5 08-FEB-17 2C2Z 1 SOURCE
REVDAT 4 20-JUL-11 2C2Z 1 COMPND REVDAT REMARK
REVDAT 3 13-JUL-11 2C2Z 1 VERSN
REVDAT 2 24-FEB-09 2C2Z 1 VERSN
REVDAT 1 20-SEP-06 2C2Z 0
JRNL AUTH O.D.EKICI,Z.Z.LI,A.J.CAMPBELL,K.E.JAMES,J.L.ASGIAN,
JRNL AUTH 2 J.MIKOLAJCZYK,G.S.SALVESEN,R.GANESAN,S.JELAKOVIC,
JRNL AUTH 3 M.G.GRUTTER,J.C.POWERS
JRNL TITL DESIGN, SYNTHESIS, AND EVALUATION OF AZA-PEPTIDE MICHAEL
JRNL TITL 2 ACCEPTORS AS SELECTIVE AND POTENT INHIBITORS OF CASPASES-2,
JRNL TITL 3 -3, -6, -7, -8, -9, AND - 10.
JRNL REF J.MED.CHEM. V. 49 5728 2006
JRNL REFN ISSN 0022-2623
JRNL PMID 16970398
JRNL DOI 10.1021/JM0601405
REMARK 2
REMARK 2 RESOLUTION. 1.95 ANGSTROMS.
REMARK 3
REMARK 3 REFINEMENT.
REMARK 3 PROGRAM : CNS 1.1
REMARK 3 AUTHORS : BRUNGER,ADAMS,CLORE,DELANO,GROS,GROSSE-
REMARK 3 : KUNSTLEVE,JIANG,KUSZEWSKI,NILGES,PANNU,
REMARK 3 : READ,RICE,SIMONSON,WARREN
REMARK 3
REMARK 3 REFINEMENT TARGET : NULL
REMARK 3
REMARK 3 DATA USED IN REFINEMENT.
REMARK 3 RESOLUTION RANGE HIGH (ANGSTROMS) : 1.95
REMARK 3 RESOLUTION RANGE LOW (ANGSTROMS) : 10.00
REMARK 3 DATA CUTOFF (SIGMA(F)) : 0.000
REMARK 3 DATA CUTOFF HIGH (ABS(F)) : 2150768.420
REMARK 3 DATA CUTOFF LOW (ABS(F)) : NULL
REMARK 3 COMPLETENESS (WORKING+TEST) (%) : 99.5
REMARK 3 NUMBER OF REFLECTIONS : 21815
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 SET) : 0.171
REMARK 3 FREE R VALUE : 0.187
REMARK 3 FREE R VALUE TEST SET SIZE (%) : 3.000
REMARK 3 FREE R VALUE TEST SET COUNT : 648
REMARK 3 ESTIMATED ERROR OF FREE R VALUE : 0.007
REMARK 3
REMARK 3 FIT IN THE HIGHEST RESOLUTION BIN.
REMARK 3 TOTAL NUMBER OF BINS USED : 6
REMARK 3 BIN RESOLUTION RANGE HIGH (A) : 1.95
REMARK 3 BIN RESOLUTION RANGE LOW (A) : 2.07
REMARK 3 BIN COMPLETENESS (WORKING+TEST) (%) : 100.00
REMARK 3 REFLECTIONS IN BIN (WORKING SET) : 3473
REMARK 3 BIN R VALUE (WORKING SET) : 0.1800
REMARK 3 BIN FREE R VALUE : 0.1980
REMARK 3 BIN FREE R VALUE TEST SET SIZE (%) : 2.90
REMARK 3 BIN FREE R VALUE TEST SET COUNT : 104
REMARK 3 ESTIMATED ERROR OF BIN FREE R VALUE : 0.019
REMARK 3
REMARK 3 NUMBER OF NON-HYDROGEN ATOMS USED IN REFINEMENT.
REMARK 3 PROTEIN ATOMS : 1968
REMARK 3 NUCLEIC ACID ATOMS : 0
REMARK 3 HETEROGEN ATOMS : 8
REMARK 3 SOLVENT ATOMS : 324
REMARK 3
REMARK 3 B VALUES.
REMARK 3 FROM WILSON PLOT (A**2) : 8.00
REMARK 3 MEAN B VALUE (OVERALL, A**2) : 19.50
REMARK 3 OVERALL ANISOTROPIC B VALUE.
REMARK 3 B11 (A**2) : 2.75000
REMARK 3 B22 (A**2) : 2.75000
REMARK 3 B33 (A**2) : -5.50000
REMARK 3 B12 (A**2) : -0.09000
REMARK 3 B13 (A**2) : 0.00000
REMARK 3 B23 (A**2) : 0.00000
REMARK 3
REMARK 3 ESTIMATED COORDINATE ERROR.
REMARK 3 ESD FROM LUZZATI PLOT (A) : 0.18
REMARK 3 ESD FROM SIGMAA (A) : 0.07
REMARK 3 LOW RESOLUTION CUTOFF (A) : 5.00
REMARK 3
REMARK 3 CROSS-VALIDATED ESTIMATED COORDINATE ERROR.
REMARK 3 ESD FROM C-V LUZZATI PLOT (A) : 0.20
REMARK 3 ESD FROM C-V SIGMAA (A) : 0.07
REMARK 3
REMARK 3 RMS DEVIATIONS FROM IDEAL VALUES.
REMARK 3 BOND LENGTHS (A) : 0.006
REMARK 3 BOND ANGLES (DEGREES) : 1.30
REMARK 3 DIHEDRAL ANGLES (DEGREES) : 22.70
REMARK 3 IMPROPER ANGLES (DEGREES) : 0.83
REMARK 3
REMARK 3 ISOTROPIC THERMAL MODEL : RESTRAINED
REMARK 3
REMARK 3 ISOTROPIC THERMAL FACTOR RESTRAINTS. RMS SIGMA
REMARK 3 MAIN-CHAIN BOND (A**2) : NULL ; NULL
REMARK 3 MAIN-CHAIN ANGLE (A**2) : NULL ; NULL
REMARK 3 SIDE-CHAIN BOND (A**2) : NULL ; NULL
REMARK 3 SIDE-CHAIN ANGLE (A**2) : NULL ; NULL
REMARK 3
REMARK 3 BULK SOLVENT MODELING.
REMARK 3 METHOD USED : FLAT MODEL
REMARK 3 KSOL : 0.45
REMARK 3 BSOL : 63.50
REMARK 3
REMARK 3 NCS MODEL : NULL
REMARK 3
REMARK 3 NCS RESTRAINTS. RMS SIGMA/WEIGHT
REMARK 3 GROUP 1 POSITIONAL (A) : NULL ; NULL
REMARK 3 GROUP 1 B-FACTOR (A**2) : NULL ; NULL
REMARK 3
REMARK 3 PARAMETER FILE 1 : PROTEIN_REP.PARAM
REMARK 3 PARAMETER FILE 2 : WATER_REP.PARAM
REMARK 3 PARAMETER FILE 3 : DTD.PAR
REMARK 3 PARAMETER FILE 4 : NULL
REMARK 3 TOPOLOGY FILE 1 : PROTEIN.TOP
REMARK 3 TOPOLOGY FILE 2 : WATER.TOP
REMARK 3 TOPOLOGY FILE 3 : DTD.TOP
REMARK 3 TOPOLOGY FILE 4 : NULL
REMARK 3
REMARK 3 OTHER REFINEMENT REMARKS: MISSING RESIDUES A216-222, A372-374,
REMARK 3 B374-389
REMARK 4
REMARK 4 2C2Z COMPLIES WITH FORMAT V. 3.30, 13-JUL-11
REMARK 100
REMARK 100 THIS ENTRY HAS BEEN PROCESSED BY PDBE ON 03-OCT-05.
REMARK 100 THE PDBE ID CODE IS EBI-25835.
REMARK 200
REMARK 200 EXPERIMENTAL DETAILS
REMARK 200 EXPERIMENT TYPE : X-RAY DIFFRACTION
REMARK 200 DATE OF DATA COLLECTION : 21-APR-05
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 : SLS
REMARK 200 BEAMLINE : X06SA
REMARK 200 X-RAY GENERATOR MODEL : NULL
REMARK 200 MONOCHROMATIC OR LAUE (M/L) : M
REMARK 200 WAVELENGTH OR RANGE (A) : 0.90001
REMARK 200 MONOCHROMATOR : NULL
REMARK 200 OPTICS : NULL
REMARK 200
REMARK 200 DETECTOR TYPE : CCD
REMARK 200 DETECTOR MANUFACTURER : MARRESEARCH
REMARK 200 INTENSITY-INTEGRATION SOFTWARE : XDS
REMARK 200 DATA SCALING SOFTWARE : XSCALE
REMARK 200
REMARK 200 NUMBER OF UNIQUE REFLECTIONS : 22937
REMARK 200 RESOLUTION RANGE HIGH (A) : 1.920
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 (%) : 98.9
REMARK 200 DATA REDUNDANCY : 7.800
REMARK 200 R MERGE (I) : 0.05000
REMARK 200 R SYM (I) : NULL
REMARK 200 <I/SIGMA(I)> FOR THE DATA SET : 29.6100
REMARK 200
REMARK 200 IN THE HIGHEST RESOLUTION SHELL.
REMARK 200 HIGHEST RESOLUTION SHELL, RANGE HIGH (A) : 1.92
REMARK 200 HIGHEST RESOLUTION SHELL, RANGE LOW (A) : 2.02
REMARK 200 COMPLETENESS FOR SHELL (%) : 99.6
REMARK 200 DATA REDUNDANCY IN SHELL : 7.55
REMARK 200 R MERGE FOR SHELL (I) : 0.09000
REMARK 200 R SYM FOR SHELL (I) : NULL
REMARK 200 <I/SIGMA(I)> FOR SHELL : 20.380
REMARK 200
REMARK 200 DIFFRACTION PROTOCOL: SINGLE WAVELENGTH
REMARK 200 METHOD USED TO DETERMINE THE STRUCTURE: OTHER
REMARK 200 SOFTWARE USED: NULL
REMARK 200 STARTING MODEL: NULL
REMARK 200
REMARK 200 REMARK: NULL
REMARK 280
REMARK 280 CRYSTAL
REMARK 280 SOLVENT CONTENT, VS (%): 48.00
REMARK 280 MATTHEWS COEFFICIENT, VM (ANGSTROMS**3/DA): 2.36
REMARK 280
REMARK 280 CRYSTALLIZATION CONDITIONS: 1.4M SODIUM CITRATE, 100MM HEPES PH 8.0
REMARK 290
REMARK 290 CRYSTALLOGRAPHIC SYMMETRY
REMARK 290 SYMMETRY OPERATORS FOR SPACE GROUP: P 31 2 1
REMARK 290
REMARK 290 SYMOP SYMMETRY
REMARK 290 NNNMMM OPERATOR
REMARK 290 1555 X,Y,Z
REMARK 290 2555 -Y,X-Y,Z+1/3
REMARK 290 3555 -X+Y,-X,Z+2/3
REMARK 290 4555 Y,X,-Z
REMARK 290 5555 X-Y,-Y,-Z+2/3
REMARK 290 6555 -X,-X+Y,-Z+1/3
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 -0.500000 -0.866025 0.000000 0.00000
REMARK 290 SMTRY2 2 0.866025 -0.500000 0.000000 0.00000
REMARK 290 SMTRY3 2 0.000000 0.000000 1.000000 43.31333
REMARK 290 SMTRY1 3 -0.500000 0.866025 0.000000 0.00000
REMARK 290 SMTRY2 3 -0.866025 -0.500000 0.000000 0.00000
REMARK 290 SMTRY3 3 0.000000 0.000000 1.000000 86.62667
REMARK 290 SMTRY1 4 -0.500000 0.866025 0.000000 0.00000
REMARK 290 SMTRY2 4 0.866025 0.500000 0.000000 0.00000
REMARK 290 SMTRY3 4 0.000000 0.000000 -1.000000 0.00000
REMARK 290 SMTRY1 5 1.000000 0.000000 0.000000 0.00000
REMARK 290 SMTRY2 5 0.000000 -1.000000 0.000000 0.00000
REMARK 290 SMTRY3 5 0.000000 0.000000 -1.000000 86.62667
REMARK 290 SMTRY1 6 -0.500000 -0.866025 0.000000 0.00000
REMARK 290 SMTRY2 6 -0.866025 0.500000 0.000000 0.00000
REMARK 290 SMTRY3 6 0.000000 0.000000 -1.000000 43.31333
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: HEXAMERIC
REMARK 350 SOFTWARE DETERMINED QUATERNARY STRUCTURE: HEXAMERIC
REMARK 350 SOFTWARE USED: PQS
REMARK 350 APPLY THE FOLLOWING TO CHAINS: A, C, 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 350 BIOMT1 2 -0.500000 -0.866025 0.000000 0.00000
REMARK 350 BIOMT2 2 -0.866025 0.500000 0.000000 0.00000
REMARK 350 BIOMT3 2 0.000000 0.000000 -1.000000 43.31333
REMARK 400
REMARK 400 COMPOUND
REMARK 400 THE INITIAL LIGAND USED IN THE EXPERIMENT WAS CBZ-LETAD-CH=CH-CO-
REMARK 400 TETRAHYDROQUINOLINE. UPON REACTION, THE DOUBLE BOND OPENED UP AND
REMARK 400 FORMED A COVALENT BOND BETWEEN ATOM C10 OF RESIDUE MX5 5 OF CHAIN C
REMARK 400 AND ATOM SG OF CYS 360 OF CHAIN A.
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 216
REMARK 465 GLY A 217
REMARK 465 GLU A 218
REMARK 465 SER A 219
REMARK 465 GLN A 220
REMARK 465 THR A 221
REMARK 465 LEU A 222
REMARK 465 THR A 373
REMARK 465 ASP A 374
REMARK 465 MET B 374
REMARK 465 ALA B 375
REMARK 465 GLU B 376
REMARK 465 GLU B 377
REMARK 465 GLN B 378
REMARK 465 PRO B 379
REMARK 465 TYR B 380
REMARK 465 LEU B 381
REMARK 465 GLU B 382
REMARK 465 MET B 383
REMARK 465 ASP B 384
REMARK 465 LEU B 385
REMARK 465 SER B 386
REMARK 465 SER B 387
REMARK 465 PRO B 388
REMARK 465 GLN B 389
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 GLU A 372 CA C O CB CG CD OE1
REMARK 470 GLU A 372 OE2
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 286 79.98 46.66
REMARK 500 ASN B 408 -15.71 78.02
REMARK 500 GLU B 417 -31.95 -133.52
REMARK 500
REMARK 500 REMARK: NULL
REMARK 525
REMARK 525 SOLVENT
REMARK 525
REMARK 525 THE SOLVENT MOLECULES HAVE CHAIN IDENTIFIERS THAT
REMARK 525 INDICATE THE POLYMER CHAIN WITH WHICH THEY ARE MOST
REMARK 525 CLOSELY ASSOCIATED. THE REMARK LISTS ALL THE SOLVENT
REMARK 525 MOLECULES WHICH ARE MORE THAN 5A AWAY FROM THE
REMARK 525 NEAREST POLYMER CHAIN (M = MODEL NUMBER;
REMARK 525 RES=RESIDUE NAME; C=CHAIN IDENTIFIER; SSEQ=SEQUENCE
REMARK 525 NUMBER; I=INSERTION CODE):
REMARK 525
REMARK 525 M RES CSSEQI
REMARK 525 HOH A2172 DISTANCE = 5.84 ANGSTROMS
REMARK 525 HOH B2027 DISTANCE = 5.31 ANGSTROMS
REMARK 525 HOH B2034 DISTANCE = 5.07 ANGSTROMS
REMARK 525 HOH B2100 DISTANCE = 5.52 ANGSTROMS
REMARK 800
REMARK 800 SITE
REMARK 800 SITE_IDENTIFIER: AC1
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: BINDING SITE FOR RESIDUE DTD B 1480
REMARK 800
REMARK 800 SITE_IDENTIFIER: AC2
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: BINDING SITE FOR CHAIN C OF AZA-PEPTIDE
REMARK 800 INHIBITOR (5S,8R,11S)-8-(2-CARBOXYETHYL)-14-[4-(3,4-
REMARK 800 DIHYDROQUINOLIN-1(2H)-YL)-4-OXOBUTANOYL]-11-[(1R)-1-HYDROXYETHYL]
REMARK 800 -5-(2-METHYLPROPYL)-3,6,9,12-TETRAOXO-1-PHENYL-2-OXA-4,7,10,13,
REMARK 800 14-PENTAAZAHEXADECAN-16-OIC ACID
REMARK 900
REMARK 900 RELATED ENTRIES
REMARK 900 RELATED ID: 1F9E RELATED DB: PDB
REMARK 900 CASPASE-8 SPECIFICITY PROBED AT SUBSITE S4 :
REMARK 900 CRYSTALSTRUCTURE OF THE CASPASE-8-Z-DEVD -CHO
REMARK 900 RELATED ID: 1I4E RELATED DB: PDB
REMARK 900 CRYSTAL STRUCTURE OF THE CASPASE-8/P35 COMPLEX
REMARK 900 RELATED ID: 1QDU RELATED DB: PDB
REMARK 900 CRYSTAL STRUCTURE OF THE COMPLEX OF CASPASE -8 WITH THE
REMARK 900 TRIPEPTIDE KETONE INHIBITOR ZEVD-DCBMK
REMARK 900 RELATED ID: 1QTN RELATED DB: PDB
REMARK 900 CRYSTAL STRUCTURE OF THE COMPLEX OF CASPASE -8 WITH THE
REMARK 900 TETRAPEPTIDE INHIBITOR ACE-IETD -ALDEHYDE
REMARK 900 RELATED ID: 2FUN RELATED DB: PDB
REMARK 900 ALTERNATIVE P35-CASPASE-8 COMPLEX
DBREF 2C2Z A 216 217 PDB 2C2Z 2C2Z 216 217
DBREF 2C2Z A 218 374 UNP Q14790 CASP8_HUMAN 218 374
DBREF 2C2Z B 374 375 PDB 2C2Z 2C2Z 374 375
DBREF 2C2Z B 376 479 UNP Q14790 CASP8_HUMAN 376 479
DBREF 2C2Z C 1 5 PDB 2C2Z 2C2Z 1 5
SEQRES 1 A 159 MET GLY GLU SER GLN THR LEU ASP LYS VAL TYR GLN MET
SEQRES 2 A 159 LYS SER LYS PRO ARG GLY TYR CYS LEU ILE ILE ASN ASN
SEQRES 3 A 159 HIS ASN PHE ALA LYS ALA ARG GLU LYS VAL PRO LYS LEU
SEQRES 4 A 159 HIS SER ILE ARG ASP ARG ASN GLY THR HIS LEU ASP ALA
SEQRES 5 A 159 GLY ALA LEU THR THR THR PHE GLU GLU LEU HIS PHE GLU
SEQRES 6 A 159 ILE LYS PRO HIS ASP ASP CYS THR VAL GLU GLN ILE TYR
SEQRES 7 A 159 GLU ILE LEU LYS ILE TYR GLN LEU MET ASP HIS SER ASN
SEQRES 8 A 159 MET ASP CYS PHE ILE CYS CYS ILE LEU SER HIS GLY ASP
SEQRES 9 A 159 LYS GLY ILE ILE TYR GLY THR ASP GLY GLN GLU ALA PRO
SEQRES 10 A 159 ILE TYR GLU LEU THR SER GLN PHE THR GLY LEU LYS CYS
SEQRES 11 A 159 PRO SER LEU ALA GLY LYS PRO LYS VAL PHE PHE ILE GLN
SEQRES 12 A 159 ALA CYS GLN GLY ASP ASN TYR GLN LYS GLY ILE PRO VAL
SEQRES 13 A 159 GLU THR ASP
SEQRES 1 B 106 MET ALA GLU GLU GLN PRO TYR LEU GLU MET ASP LEU SER
SEQRES 2 B 106 SER PRO GLN THR ARG TYR ILE PRO ASP GLU ALA ASP PHE
SEQRES 3 B 106 LEU LEU GLY MET ALA THR VAL ASN ASN CYS VAL SER TYR
SEQRES 4 B 106 ARG ASN PRO ALA GLU GLY THR TRP TYR ILE GLN SER LEU
SEQRES 5 B 106 CYS GLN SER LEU ARG GLU ARG CYS PRO ARG GLY ASP ASP
SEQRES 6 B 106 ILE LEU THR ILE LEU THR GLU VAL ASN TYR GLU VAL SER
SEQRES 7 B 106 ASN LYS ASP ASP LYS LYS ASN MET GLY LYS GLN MET PRO
SEQRES 8 B 106 GLN PRO THR PHE THR LEU ARG LYS LYS LEU VAL PHE PRO
SEQRES 9 B 106 SER ASP
SEQRES 1 C 5 PHQ LEU GLU THR MX5
HET PHQ C 1 10
HET MX5 C 5 22
HET DTD B1480 8
HETNAM PHQ BENZYL CHLOROCARBONATE
HETNAM MX5 {1-[4-(3,4-DIHYDROQUINOLIN-1(2H)-YL)-4-
HETNAM 2 MX5 OXOBUTANOYL]HYDRAZINO}ACETIC ACID
HETNAM DTD DITHIANE DIOL
HETSYN MX5 {N-[(E)-4-(3,4-DIHYDRO-2H-QUINOLIN-1-YL)-4-OXO-BUT-2-
HETSYN 2 MX5 ENOYL]-HYDRAZINO}-ACETIC ACID
FORMUL 3 PHQ C8 H7 CL O2
FORMUL 3 MX5 C15 H19 N3 O4
FORMUL 4 DTD C4 H8 O2 S2
FORMUL 5 HOH *324(H2 O)
HELIX 1 1 PHE A 244 VAL A 251 1 8
HELIX 2 2 PRO A 252 HIS A 255 5 4
HELIX 3 3 GLY A 262 LEU A 277 1 16
HELIX 4 4 THR A 288 MET A 302 1 15
HELIX 5 5 ILE A 333 SER A 338 1 6
HELIX 6 6 GLN A 339 THR A 341 5 3
HELIX 7 7 CYS A 345 ALA A 349 5 5
HELIX 8 8 TRP B 420 CYS B 433 1 14
HELIX 9 9 PRO B 434 GLY B 436 5 3
HELIX 10 10 ASP B 438 ASN B 452 1 15
HELIX 11 11 LYS B 456 MET B 459 5 4
SHEET 1 AA 6 GLU A 280 ASP A 285 0
SHEET 2 AA 6 TYR A 235 ASN A 240 1 O CYS A 236 N LYS A 282
SHEET 3 AA 6 PHE A 310 LEU A 315 1 O ILE A 311 N LEU A 237
SHEET 4 AA 6 LYS A 353 GLN A 358 1 O VAL A 354 N CYS A 312
SHEET 5 AA 6 PHE B 399 MET B 403 1 O LEU B 400 N PHE A 355
SHEET 6 AA 6 GLN B 465 PHE B 468 -1 O GLN B 465 N MET B 403
SHEET 1 AB 3 GLY A 318 ASP A 319 0
SHEET 2 AB 3 ILE A 322 TYR A 324 -1 O ILE A 322 N ASP A 319
SHEET 3 AB 3 GLU A 330 PRO A 332 -1 O ALA A 331 N ILE A 323
SHEET 1 BA 2 ARG B 413 ASN B 414 0
SHEET 2 BA 2 GLY B 418 THR B 419 -1 O GLY B 418 N ASN B 414
LINK C1 PHQ C 1 N LEU C 2 1555 1555 1.32
LINK C THR C 4 N20 MX5 C 5 1555 1555 1.31
LINK SG CYS A 360 C10 MX5 C 5 1555 1555 1.87
CISPEP 1 LYS A 231 PRO A 232 0 0.13
SITE 1 AC1 10 TYR A 334 THR A 337 HOH A2168 GLU B 396
SITE 2 AC1 10 PHE B 399 LEU B 401 GLN B 465 THR B 469
SITE 3 AC1 10 HOH B2103 HOH B2104
SITE 1 AC2 28 LEU A 254 ARG A 260 SER A 316 HIS A 317
SITE 2 AC2 28 GLY A 318 TYR A 324 LEU A 343 LYS A 344
SITE 3 AC2 28 GLN A 358 ALA A 359 CYS A 360 HOH A2051
SITE 4 AC2 28 SER B 411 TYR B 412 ARG B 413 ASN B 414
SITE 5 AC2 28 PRO B 415 ALA B 416 THR B 419 TRP B 420
SITE 6 AC2 28 HOH B2037 HOH C2216 HOH C2217 HOH C2218
SITE 7 AC2 28 HOH C2220 HOH C2221 HOH C2222 HOH C2224
CRYST1 62.520 62.520 129.940 90.00 90.00 120.00 P 31 2 1 6
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 0.015995 0.009235 0.000000 0.00000
SCALE2 0.000000 0.018469 0.000000 0.00000
SCALE3 0.000000 0.000000 0.007696 0.00000
(ATOM LINES ARE NOT SHOWN.)
END