HEADER HYDROLASE/HYDROLASE INHIBITOR 16-FEB-15 4Y8Y
TITLE FACTOR XIA IN COMPLEX WITH THE INHIBITOR METHYL (4-{4-CHLORO-2-[(1S)-
TITLE 2 1-({(2E)-3-[5-CHLORO-2-(1H-TETRAZOL-1-YL)PHENYL]PROP-2-ENOYL}AMINO)-
TITLE 3 3-(MORPHOLIN-4-YL)-3-OXOPROPYL]-1H-IMIDAZOL-5-YL}PHENYL)CARBAMATE
COMPND MOL_ID: 1;
COMPND 2 MOLECULE: COAGULATION FACTOR XIA;
COMPND 3 CHAIN: A;
COMPND 4 FRAGMENT: LIGHT CHAIN (UNP RESIDUES 388-625);
COMPND 5 SYNONYM: FXI, PLASMA THROMBOPLASTIN ANTECEDENT, PTA;
COMPND 6 EC: 3.4.21.27;
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: F11;
SOURCE 6 EXPRESSION_SYSTEM: ESCHERICHIA COLI BL21(DE3);
SOURCE 7 EXPRESSION_SYSTEM_TAXID: 469008;
SOURCE 8 EXPRESSION_SYSTEM_VECTOR_TYPE: PLASMID;
SOURCE 9 EXPRESSION_SYSTEM_PLASMID: PET14B
KEYWDS HYDROLASE, SERINE PROTEASE, BLOOD COAGULATION FACTOR, PROTEIN
KEYWDS 2 INHIBITOR COMPLEX, HYDROLASE-HYDROLASE INHIBITOR COMPLEX
EXPDTA X-RAY DIFFRACTION
AUTHOR A.WEI
REVDAT 3 27-SEP-23 4Y8Y 1 COMPND HETNAM
REVDAT 2 18-APR-18 4Y8Y 1 COMPND SOURCE JRNL REMARK
REVDAT 2 2 1 HETNAM
REVDAT 1 27-MAY-15 4Y8Y 0
JRNL AUTH Z.HU,P.C.WONG,P.J.GILLIGAN,W.HAN,K.B.PABBISETTY,J.M.BOZARTH,
JRNL AUTH 2 E.J.CRAIN,T.HARPER,J.M.LUETTGEN,J.E.MYERS,V.RAMAMURTHY,
JRNL AUTH 3 K.A.ROSSI,S.SHERIFF,C.A.WATSON,A.WEI,J.J.ZHENG,D.A.SEIFFERT,
JRNL AUTH 4 R.R.WEXLER,M.L.QUAN
JRNL TITL DISCOVERY OF A POTENT PARENTERALLY ADMINISTERED FACTOR XIA
JRNL TITL 2 INHIBITOR WITH HYDROXYQUINOLIN-2(1H)-ONE AS THE P2' MOIETY.
JRNL REF ACS MED CHEM LETT V. 6 590 2015
JRNL REFN ISSN 1948-5875
JRNL PMID 26005539
JRNL DOI 10.1021/ACSMEDCHEMLETT.5B00066
REMARK 1
REMARK 1 REFERENCE 1
REMARK 1 AUTH M.L.QUAN,P.C.WONG,C.WANG,F.WOERNER,J.M.SMALLHEER,
REMARK 1 AUTH 2 F.A.BARBERA,J.M.BOZARTH,R.L.BROWN,M.R.HARPEL,J.M.LUETTGEN,
REMARK 1 AUTH 3 P.E.MORIN,T.PETERSON,V.RAMAMURTHY,A.R.RENDINA,K.A.ROSSI,
REMARK 1 AUTH 4 C.A.WATSON,A.WEI,G.ZHANG,D.SEIFFERT,R.R.WEXLER
REMARK 1 TITL TETRAHYDROQUINOLINE DERIVATIVES AS POTENT AND SELECTIVE
REMARK 1 TITL 2 FACTOR XIA INHIBITORS
REMARK 1 REF J.MED.CHEM. V. 57 955 2014
REMARK 1 REFN ISSN 0022-2623
REMARK 1 REFERENCE 2
REMARK 1 AUTH J.J.HANGELAND,T.J.FRIENDS,K.A.ROSSI,J.M.SMALLHEER,C.WANG,
REMARK 1 AUTH 2 Z.SUN,J.R.CORTE,T.FANG,P.C.WONG,A.R.RENDINA,F.A.BARBERA,
REMARK 1 AUTH 3 J.M.BOZARTH,J.M.LUETTGEN,C.A.WATSON,G.ZHANG,A.WEI,
REMARK 1 AUTH 4 V.RAMAMURTHY,P.E.MORIN,G.S.BISACCHI,S.SUBRAMANIAM,
REMARK 1 AUTH 5 P.ARUNACHALAM,A.MATHUR,D.A.SEIFFERT,R.R.WEXLER,M.L.QUAN
REMARK 1 TITL PHENYLIMIDAZOLES AS POTENT AND SELECTIVE INHIBITORS OF
REMARK 1 TITL 2 COAGULATION FACTOR XIA WITH IN VIVO ANTITHROMBOTIC ACTIVITY
REMARK 1 REF J.MED.CHEM. V. 57 9915 2014
REMARK 1 REFN ISSN 0022-2623
REMARK 1 REFERENCE 3
REMARK 1 AUTH J.R.CORTE,T.FANG,J.J.HANGELAND,T.J.FRIENDS,A.R.RENDINA,
REMARK 1 AUTH 2 J.M.LUETTGEN,J.M.BOZARTH,F.A.BARBERA,K.A.ROSSI,A.WEI,
REMARK 1 AUTH 3 V.RAMAMURTHY,P.E.MORIN,D.A.SEIFFERT,R.R.WEXLER,M.L.QUAN
REMARK 1 TITL PYRIDINE AND PYRIDINONE-BASED FACTOR XIA INHIBITORS
REMARK 1 REF BIOORG.MED.CHEM.LETT. V. 25 925 2015
REMARK 1 REFN ISSN 0960-894X
REMARK 1 REFERENCE 4
REMARK 1 AUTH D.J.PINTO,J.M.SMALLHEER,J.R.CORTE,E.J.AUSTIN,C.WANG,T.FANG,
REMARK 1 AUTH 2 L.M.SMITH,K.A.ROSSI,A.R.RENDINA,J.M.BOZARTH,G.ZHANG,A.WEI,
REMARK 1 AUTH 3 V.RAMAMURTHY,S.SHERIFF,J.E.MYERS,P.E.MORIN,J.M.LUETTGEN,
REMARK 1 AUTH 4 D.A.SEIFFERT,M.L.QUAN,R.R.WEXLER
REMARK 1 TITL STRUCTURE-BASED DESIGN OF INHIBITORS OF COAGULATION FACTOR
REMARK 1 TITL 2 XIA WITH NOVEL P1 MOIETIES.
REMARK 1 REF BIOORG.MED.CHEM.LETT. V. 25 1635 2015
REMARK 1 REFN ESSN 1464-3405
REMARK 1 PMID 25728130
REMARK 1 DOI 10.1016/J.BMCL.2015.01.028
REMARK 2
REMARK 2 RESOLUTION. 2.60 ANGSTROMS.
REMARK 3
REMARK 3 REFINEMENT.
REMARK 3 PROGRAM : BUSTER-TNT BUSTER 2.11.5
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) : 2.60
REMARK 3 RESOLUTION RANGE LOW (ANGSTROMS) : 28.79
REMARK 3 DATA CUTOFF (SIGMA(F)) : 0.000
REMARK 3 COMPLETENESS FOR RANGE (%) : 82.2
REMARK 3 NUMBER OF REFLECTIONS : 10081
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) : 0.201
REMARK 3 R VALUE (WORKING SET) : 0.196
REMARK 3 FREE R VALUE : 0.241
REMARK 3 FREE R VALUE TEST SET SIZE (%) : 10.400
REMARK 3 FREE R VALUE TEST SET COUNT : 1048
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 : 5
REMARK 3 BIN RESOLUTION RANGE HIGH (ANGSTROMS) : 2.60
REMARK 3 BIN RESOLUTION RANGE LOW (ANGSTROMS) : 2.91
REMARK 3 BIN COMPLETENESS (WORKING+TEST) (%) : 82.15
REMARK 3 REFLECTIONS IN BIN (WORKING + TEST SET) : 2181
REMARK 3 BIN R VALUE (WORKING + TEST SET) : 0.2828
REMARK 3 REFLECTIONS IN BIN (WORKING SET) : 1961
REMARK 3 BIN R VALUE (WORKING SET) : 0.2735
REMARK 3 BIN FREE R VALUE : 0.3615
REMARK 3 BIN FREE R VALUE TEST SET SIZE (%) : 10.09
REMARK 3 BIN FREE R VALUE TEST SET COUNT : 220
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 : 1850
REMARK 3 NUCLEIC ACID ATOMS : 0
REMARK 3 HETEROGEN ATOMS : 82
REMARK 3 SOLVENT ATOMS : 78
REMARK 3
REMARK 3 B VALUES.
REMARK 3 FROM WILSON PLOT (A**2) : 47.91
REMARK 3 MEAN B VALUE (OVERALL, A**2) : 23.33
REMARK 3 OVERALL ANISOTROPIC B VALUE.
REMARK 3 B11 (A**2) : -1.61100
REMARK 3 B22 (A**2) : -1.61100
REMARK 3 B33 (A**2) : 3.22200
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 ESTIMATED COORDINATE ERROR.
REMARK 3 ESD FROM LUZZATI PLOT (A) : 0.339
REMARK 3 DPI (BLOW EQ-10) BASED ON R VALUE (A) : 0.606
REMARK 3 DPI (BLOW EQ-9) BASED ON FREE R VALUE (A) : 0.299
REMARK 3 DPI (CRUICKSHANK) BASED ON R VALUE (A) : 0.553
REMARK 3 DPI (CRUICKSHANK) BASED ON FREE R VALUE (A) : 0.297
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 : 0.909
REMARK 3 CORRELATION COEFFICIENT FO-FC FREE : 0.854
REMARK 3
REMARK 3 NUMBER OF GEOMETRIC FUNCTION TERMS DEFINED : 15
REMARK 3 TERM COUNT WEIGHT FUNCTION.
REMARK 3 BOND LENGTHS : 2003 ; 2.000 ; HARMONIC
REMARK 3 BOND ANGLES : 2732 ; 2.000 ; HARMONIC
REMARK 3 TORSION ANGLES : 672 ; 2.000 ; SINUSOIDAL
REMARK 3 TRIGONAL CARBON PLANES : 40 ; 2.000 ; HARMONIC
REMARK 3 GENERAL PLANES : 329 ; 5.000 ; HARMONIC
REMARK 3 ISOTROPIC THERMAL FACTORS : 2003 ; 20.000 ; HARMONIC
REMARK 3 BAD NON-BONDED CONTACTS : NULL ; NULL ; NULL
REMARK 3 IMPROPER TORSIONS : NULL ; NULL ; NULL
REMARK 3 PSEUDOROTATION ANGLES : NULL ; NULL ; NULL
REMARK 3 CHIRAL IMPROPER TORSION : 249 ; 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 : 2283 ; 4.000 ; SEMIHARMONIC
REMARK 3
REMARK 3 RMS DEVIATIONS FROM IDEAL VALUES.
REMARK 3 BOND LENGTHS (A) : 0.010
REMARK 3 BOND ANGLES (DEGREES) : 1.21
REMARK 3 PEPTIDE OMEGA TORSION ANGLES (DEGREES) : 3.19
REMARK 3 OTHER TORSION ANGLES (DEGREES) : 18.61
REMARK 3
REMARK 3 TLS DETAILS
REMARK 3 NUMBER OF TLS GROUPS : NULL
REMARK 3
REMARK 3 OTHER REFINEMENT REMARKS: NULL
REMARK 4
REMARK 4 4Y8Y COMPLIES WITH FORMAT V. 3.30, 13-JUL-11
REMARK 100
REMARK 100 THIS ENTRY HAS BEEN PROCESSED BY RCSB ON 03-MAR-15.
REMARK 100 THE DEPOSITION ID IS D_1000206746.
REMARK 200
REMARK 200 EXPERIMENTAL DETAILS
REMARK 200 EXPERIMENT TYPE : X-RAY DIFFRACTION
REMARK 200 DATE OF DATA COLLECTION : 27-OCT-06
REMARK 200 TEMPERATURE (KELVIN) : 100.0
REMARK 200 PH : 4.6
REMARK 200 NUMBER OF CRYSTALS USED : 1
REMARK 200
REMARK 200 SYNCHROTRON (Y/N) : N
REMARK 200 RADIATION SOURCE : ROTATING ANODE
REMARK 200 BEAMLINE : NULL
REMARK 200 X-RAY GENERATOR MODEL : RIGAKU FR-E SUPERBRIGHT
REMARK 200 MONOCHROMATIC OR LAUE (M/L) : M
REMARK 200 WAVELENGTH OR RANGE (A) : 1.54
REMARK 200 MONOCHROMATOR : NULL
REMARK 200 OPTICS : MICROMAX CONFOCAL
REMARK 200
REMARK 200 DETECTOR TYPE : CCD
REMARK 200 DETECTOR MANUFACTURER : RIGAKU SATURN 92
REMARK 200 INTENSITY-INTEGRATION SOFTWARE : DENZO
REMARK 200 DATA SCALING SOFTWARE : SCALEPACK
REMARK 200
REMARK 200 NUMBER OF UNIQUE REFLECTIONS : 12254
REMARK 200 RESOLUTION RANGE HIGH (A) : 2.600
REMARK 200 RESOLUTION RANGE LOW (A) : 50.000
REMARK 200 REJECTION CRITERIA (SIGMA(I)) : 0.000
REMARK 200
REMARK 200 OVERALL.
REMARK 200 COMPLETENESS FOR RANGE (%) : 99.9
REMARK 200 DATA REDUNDANCY : 9.600
REMARK 200 R MERGE (I) : NULL
REMARK 200 R SYM (I) : 0.16300
REMARK 200 <I/SIGMA(I)> FOR THE DATA SET : 14.5000
REMARK 200
REMARK 200 IN THE HIGHEST RESOLUTION SHELL.
REMARK 200 HIGHEST RESOLUTION SHELL, RANGE HIGH (A) : 2.60
REMARK 200 HIGHEST RESOLUTION SHELL, RANGE LOW (A) : 2.69
REMARK 200 COMPLETENESS FOR SHELL (%) : 100.0
REMARK 200 DATA REDUNDANCY IN SHELL : 9.20
REMARK 200 R MERGE FOR SHELL (I) : 0.67400
REMARK 200 R SYM FOR SHELL (I) : NULL
REMARK 200 <I/SIGMA(I)> FOR SHELL : 3.000
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: PDB ENTRY 4TY7
REMARK 200
REMARK 200 REMARK: NULL
REMARK 280
REMARK 280 CRYSTAL
REMARK 280 SOLVENT CONTENT, VS (%): 65.69
REMARK 280 MATTHEWS COEFFICIENT, VM (ANGSTROMS**3/DA): 3.58
REMARK 280
REMARK 280 CRYSTALLIZATION CONDITIONS: 100 MM SODIUM ACETATE, PH 4.6, 26% W/V
REMARK 280 MEPEG2000, 200 MM AMMONIUM SULFATE, VAPOR DIFFUSION, HANGING
REMARK 280 DROP, TEMPERATURE 277K
REMARK 290
REMARK 290 CRYSTALLOGRAPHIC SYMMETRY
REMARK 290 SYMMETRY OPERATORS FOR SPACE GROUP: P 32 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+2/3
REMARK 290 3555 -X+Y,-X,Z+1/3
REMARK 290 4555 Y,X,-Z
REMARK 290 5555 X-Y,-Y,-Z+1/3
REMARK 290 6555 -X,-X+Y,-Z+2/3
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 70.66667
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 35.33333
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 35.33333
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 70.66667
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 TOTAL BURIED SURFACE AREA: 1670 ANGSTROM**2
REMARK 350 SURFACE AREA OF THE COMPLEX: 11140 ANGSTROM**2
REMARK 350 CHANGE IN SOLVENT FREE ENERGY: -9.0 KCAL/MOL
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 375
REMARK 375 SPECIAL POSITION
REMARK 375 THE FOLLOWING ATOMS ARE FOUND TO BE WITHIN 0.15 ANGSTROMS
REMARK 375 OF A SYMMETRY RELATED ATOM AND ARE ASSUMED TO BE ON SPECIAL
REMARK 375 POSITIONS.
REMARK 375
REMARK 375 ATOM RES CSSEQI
REMARK 375 S SO4 A 303 LIES ON A SPECIAL POSITION.
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 HIS A 246
REMARK 465 HIS A 247
REMARK 465 HIS A 248
REMARK 465 HIS A 249
REMARK 465 HIS A 250
REMARK 465 HIS A 251
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 78 CG CD OE1 OE2
REMARK 470 LYS A 126 CG CD CE NZ
REMARK 470 ASP A 128 CG OD1 OD2
REMARK 470 ARG A 129 CG CD NE CZ NH1 NH2
REMARK 470 ASN A 130 CG OD1 ND2
REMARK 470 ARG A 148 CG CD NE CZ NH1 NH2
REMARK 470 GLU A 185 CG CD OE1 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 135 79.43 -105.31
REMARK 500 ASP A 149 -153.39 -143.95
REMARK 500 TYR A 171 67.84 -119.60
REMARK 500 SER A 214 -75.40 -113.62
REMARK 500 ALA A 220 46.56 37.13
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 4D5 A 301
REMARK 800
REMARK 800 SITE_IDENTIFIER: AC2
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: binding site for residue SO4 A 302
REMARK 800
REMARK 800 SITE_IDENTIFIER: AC3
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: binding site for residue SO4 A 303
REMARK 800
REMARK 800 SITE_IDENTIFIER: AC4
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: binding site for residue EDO A 304
REMARK 800
REMARK 800 SITE_IDENTIFIER: AC5
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: binding site for residue EDO A 305
REMARK 800
REMARK 800 SITE_IDENTIFIER: AC6
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: binding site for residue EDO A 306
REMARK 800
REMARK 800 SITE_IDENTIFIER: AC7
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: binding site for residue EDO A 307
REMARK 800
REMARK 800 SITE_IDENTIFIER: AC8
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: binding site for residue EDO A 308
REMARK 800
REMARK 800 SITE_IDENTIFIER: AC9
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: binding site for residue EDO A 309
REMARK 800
REMARK 800 SITE_IDENTIFIER: AD1
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: binding site for residue EDO A 310
REMARK 900
REMARK 900 RELATED ENTRIES
REMARK 900 RELATED ID: 4Y8X RELATED DB: PDB
REMARK 900 RELATED ID: 4Y8Z RELATED DB: PDB
DBREF 4Y8Y A 16 245 UNP P03951 FA11_HUMAN 388 625
SEQADV 4Y8Y GLY A 113 UNP P03951 ASN 491 ENGINEERED MUTATION
SEQADV 4Y8Y GLY A 115 UNP P03951 THR 493 ENGINEERED MUTATION
SEQADV 4Y8Y HIS A 246 UNP P03951 EXPRESSION TAG
SEQADV 4Y8Y HIS A 247 UNP P03951 EXPRESSION TAG
SEQADV 4Y8Y HIS A 248 UNP P03951 EXPRESSION TAG
SEQADV 4Y8Y HIS A 249 UNP P03951 EXPRESSION TAG
SEQADV 4Y8Y HIS A 250 UNP P03951 EXPRESSION TAG
SEQADV 4Y8Y HIS A 251 UNP P03951 EXPRESSION TAG
SEQRES 1 A 244 ILE VAL GLY GLY THR ALA SER VAL ARG GLY GLU TRP PRO
SEQRES 2 A 244 TRP GLN VAL THR LEU HIS THR THR SER PRO THR GLN ARG
SEQRES 3 A 244 HIS LEU CYS GLY GLY SER ILE ILE GLY ASN GLN TRP ILE
SEQRES 4 A 244 LEU THR ALA ALA HIS CYS PHE TYR GLY VAL GLU SER PRO
SEQRES 5 A 244 LYS ILE LEU ARG VAL TYR SER GLY ILE LEU ASN GLN SER
SEQRES 6 A 244 GLU ILE LYS GLU ASP THR SER PHE PHE GLY VAL GLN GLU
SEQRES 7 A 244 ILE ILE ILE HIS ASP GLN TYR LYS MET ALA GLU SER GLY
SEQRES 8 A 244 TYR ASP ILE ALA LEU LEU LYS LEU GLU THR THR VAL GLY
SEQRES 9 A 244 TYR GLY ASP SER GLN ARG PRO ILE CYS LEU PRO SER LYS
SEQRES 10 A 244 GLY ASP ARG ASN VAL ILE TYR THR ASP CYS TRP VAL THR
SEQRES 11 A 244 GLY TRP GLY TYR ARG LYS LEU ARG ASP LYS ILE GLN ASN
SEQRES 12 A 244 THR LEU GLN LYS ALA LYS ILE PRO LEU VAL THR ASN GLU
SEQRES 13 A 244 GLU CYS GLN LYS ARG TYR ARG GLY HIS LYS ILE THR HIS
SEQRES 14 A 244 LYS MET ILE CYS ALA GLY TYR ARG GLU GLY GLY LYS ASP
SEQRES 15 A 244 ALA CYS LYS GLY ASP SER GLY GLY PRO LEU SER CYS LYS
SEQRES 16 A 244 HIS ASN GLU VAL TRP HIS LEU VAL GLY ILE THR SER TRP
SEQRES 17 A 244 GLY GLU GLY CYS ALA GLN ARG GLU ARG PRO GLY VAL TYR
SEQRES 18 A 244 THR ASN VAL VAL GLU TYR VAL ASP TRP ILE LEU GLU LYS
SEQRES 19 A 244 THR GLN ALA VAL HIS HIS HIS HIS HIS HIS
HET 4D5 A 301 71
HET SO4 A 302 5
HET SO4 A 303 5
HET EDO A 304 4
HET EDO A 305 4
HET EDO A 306 4
HET EDO A 307 4
HET EDO A 308 4
HET EDO A 309 4
HET EDO A 310 4
HETNAM 4D5 METHYL (4-{4-CHLORO-2-[(1S)-1-({(2E)-3-[5-CHLORO-2-(1H-
HETNAM 2 4D5 TETRAZOL-1-YL)PHENYL]PROP-2-ENOYL}AMINO)-3-(MORPHOLIN-
HETNAM 3 4D5 4-YL)-3-OXOPROPYL]-1H-IMIDAZOL-5-YL}PHENYL)CARBAMATE
HETNAM SO4 SULFATE ION
HETNAM EDO 1,2-ETHANEDIOL
HETSYN EDO ETHYLENE GLYCOL
FORMUL 2 4D5 C28 H27 CL2 N9 O5
FORMUL 3 SO4 2(O4 S 2-)
FORMUL 5 EDO 7(C2 H6 O2)
FORMUL 12 HOH *78(H2 O)
HELIX 1 AA1 ALA A 55 TYR A 58B 5 6
HELIX 2 AA2 SER A 62 LYS A 64 5 3
HELIX 3 AA3 ASN A 72 ILE A 76 5 5
HELIX 4 AA4 MET A 96 GLY A 100 5 5
HELIX 5 AA5 SER A 125 VAL A 131 5 7
HELIX 6 AA6 THR A 164 TYR A 171 1 9
HELIX 7 AA7 TYR A 234 GLN A 243 1 10
SHEET 1 AA1 8 THR A 20 ALA A 21 0
SHEET 2 AA1 8 GLN A 156 LYS A 159 -1 O LYS A 157 N THR A 20
SHEET 3 AA1 8 CYS A 136 GLY A 140 -1 N VAL A 138 O ALA A 158
SHEET 4 AA1 8 PRO A 198 HIS A 203 -1 O SER A 200 N TRP A 137
SHEET 5 AA1 8 VAL A 206 TRP A 215 -1 O VAL A 206 N HIS A 203
SHEET 6 AA1 8 GLY A 226 ASN A 230 -1 O VAL A 227 N TRP A 215
SHEET 7 AA1 8 MET A 180 ALA A 183 -1 N ILE A 181 O TYR A 228
SHEET 8 AA1 8 LEU A 162 VAL A 163 -1 N VAL A 163 O CYS A 182
SHEET 1 AA2 7 GLN A 30 THR A 35 0
SHEET 2 AA2 7 ARG A 39 GLY A 48 -1 O LEU A 41 N LEU A 33
SHEET 3 AA2 7 TRP A 51 THR A 54 -1 O LEU A 53 N SER A 45
SHEET 4 AA2 7 ALA A 104 LEU A 108 -1 O LEU A 106 N ILE A 52
SHEET 5 AA2 7 PHE A 83 ILE A 90 -1 N ILE A 89 O LEU A 105
SHEET 6 AA2 7 LEU A 65A TYR A 67 -1 N VAL A 66 O PHE A 83
SHEET 7 AA2 7 GLN A 30 THR A 35 -1 N HIS A 34 O ARG A 65B
SSBOND 1 CYS A 42 CYS A 58 1555 1555 2.02
SSBOND 2 CYS A 136 CYS A 201 1555 1555 2.05
SSBOND 3 CYS A 168 CYS A 182 1555 1555 2.02
SSBOND 4 CYS A 191 CYS A 219 1555 1555 2.04
CISPEP 1 SER A 36A PRO A 36B 0 -5.10
SITE 1 AC1 27 ARG A 39 HIS A 40 LEU A 41 HIS A 57
SITE 2 AC1 27 TYR A 58B GLY A 115 ASP A 116 LEU A 147
SITE 3 AC1 27 ILE A 151 ASP A 189 ALA A 190 CYS A 191
SITE 4 AC1 27 LYS A 192 GLY A 193 ASP A 194 SER A 195
SITE 5 AC1 27 TRP A 215 GLY A 216 GLY A 218 CYS A 219
SITE 6 AC1 27 GLY A 226 EDO A 304 EDO A 308 HOH A 426
SITE 7 AC1 27 HOH A 470 HOH A 473 HOH A 478
SITE 1 AC2 11 SER A 22 VAL A 23 ARG A 24 GLY A 25
SITE 2 AC2 11 GLU A 26 TRP A 27 ILE A 70 LEU A 71
SITE 3 AC2 11 LEU A 155 HOH A 412 HOH A 472
SITE 1 AC3 2 ARG A 170 ARG A 184B
SITE 1 AC4 3 LYS A 192 4D5 A 301 EDO A 308
SITE 1 AC5 4 ASN A 49 THR A 111 VAL A 112 TYR A 114
SITE 1 AC6 4 GLN A 73 SER A 74 ILE A 151 ASN A 153
SITE 1 AC7 2 ARG A 24 SER A 99
SITE 1 AC8 7 SER A 81 LEU A 147 GLY A 216 GLY A 218
SITE 2 AC8 7 4D5 A 301 EDO A 304 EDO A 309
SITE 1 AC9 5 GLU A 98 HIS A 174 GLY A 216 GLU A 217
SITE 2 AC9 5 EDO A 308
SITE 1 AD1 1 HIS A 178
CRYST1 79.200 79.200 106.000 90.00 90.00 120.00 P 32 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 0.012626 0.007290 0.000000 0.00000
SCALE2 0.000000 0.014580 0.000000 0.00000
SCALE3 0.000000 0.000000 0.009434 0.00000
(ATOM LINES ARE NOT SHOWN.)
END
