HEADER HYDROLASE/HYDROLASE INHIBITOR 01-JUL-16 5KOQ
TITLE DISCOVERY OF TAK-272: A NOVEL, POTENT AND ORALLY ACTIVE RENIN IN-
TITLE 2 HIBITOR
CAVEAT 5KOQ NAG B 401 HAS WRONG CHIRALITY AT ATOM C1
COMPND MOL_ID: 1;
COMPND 2 MOLECULE: RENIN;
COMPND 3 CHAIN: A, B;
COMPND 4 FRAGMENT: UNP RESIDUES 70-406;
COMPND 5 SYNONYM: ANGIOTENSINOGENASE;
COMPND 6 EC: 3.4.23.15;
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: REN;
SOURCE 6 EXPRESSION_SYSTEM: HOMO SAPIENS;
SOURCE 7 EXPRESSION_SYSTEM_COMMON: HUMAN;
SOURCE 8 EXPRESSION_SYSTEM_TAXID: 9606;
SOURCE 9 EXPRESSION_SYSTEM_CELL_LINE: HEK 293
KEYWDS PROTEIN-INHIBITOR COMPLEX, HYDROLASE-HYDROLASE INHIBITOR COMPLEX
EXPDTA X-RAY DIFFRACTION
AUTHOR G.P.SNELL,C.A.BEHNKE,K.OKADA,O.HIDEYUKI,B.-C.SANG,W.LANE
REVDAT 4 29-JUL-20 5KOQ 1 COMPND REMARK HETNAM LINK
REVDAT 4 2 1 SITE
REVDAT 3 16-NOV-16 5KOQ 1 JRNL
REVDAT 2 09-NOV-16 5KOQ 1 JRNL
REVDAT 1 02-NOV-16 5KOQ 0
JRNL AUTH Y.IMAEDA,M.TAWADA,S.SUZUKI,M.TOMIMOTO,M.KONDO,N.TARUI,
JRNL AUTH 2 T.SANADA,R.KANAGAWA,G.SNELL,C.A.BEHNKE,K.KUBO,T.KUROITA
JRNL TITL STRUCTURE-BASED DESIGN OF A NEW SERIES OF
JRNL TITL 2 N-(PIPERIDIN-3-YL)PYRIMIDINE-5-CARBOXAMIDES AS RENIN
JRNL TITL 3 INHIBITORS.
JRNL REF BIOORG.MED.CHEM. V. 24 5771 2016
JRNL REFN ESSN 1464-3391
JRNL PMID 27687967
JRNL DOI 10.1016/J.BMC.2016.09.030
REMARK 1
REMARK 1 REFERENCE 1
REMARK 1 AUTH Y.IMAEDA,H.TOKUHARA,Y.FUKASE,R.KANAGAWA,Y.KAJIMOTO,
REMARK 1 AUTH 2 K.KUSUMOTO,M.KONDO,G.SNELL,C.A.BEHNKE,T.KUROITA
REMARK 1 TITL DISCOVERY OF TAK-272: A NOVEL, POTENT, AND ORALLY ACTIVE
REMARK 1 TITL 2 RENIN INHIBITOR.
REMARK 1 REF ACS MED.CHEM.LETT. V. 7 933 2016
REMARK 1 REFN ISSN 1948-5875
REMARK 1 PMID 27774132
REMARK 1 DOI 10.1021/ACSMEDCHEMLETT.6B00251
REMARK 2
REMARK 2 RESOLUTION. 2.70 ANGSTROMS.
REMARK 3
REMARK 3 REFINEMENT.
REMARK 3 PROGRAM : REFMAC 5.8.0135
REMARK 3 AUTHORS : MURSHUDOV,SKUBAK,LEBEDEV,PANNU,STEINER,
REMARK 3 : NICHOLLS,WINN,LONG,VAGIN
REMARK 3
REMARK 3 REFINEMENT TARGET : NULL
REMARK 3
REMARK 3 DATA USED IN REFINEMENT.
REMARK 3 RESOLUTION RANGE HIGH (ANGSTROMS) : 2.70
REMARK 3 RESOLUTION RANGE LOW (ANGSTROMS) : 50.00
REMARK 3 DATA CUTOFF (SIGMA(F)) : 0.000
REMARK 3 COMPLETENESS FOR RANGE (%) : 99.1
REMARK 3 NUMBER OF REFLECTIONS : 23173
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) : 0.206
REMARK 3 R VALUE (WORKING SET) : 0.204
REMARK 3 FREE R VALUE : 0.252
REMARK 3 FREE R VALUE TEST SET SIZE (%) : 5.100
REMARK 3 FREE R VALUE TEST SET COUNT : 1244
REMARK 3
REMARK 3 FIT IN THE HIGHEST RESOLUTION BIN.
REMARK 3 TOTAL NUMBER OF BINS USED : 20
REMARK 3 BIN RESOLUTION RANGE HIGH (A) : 2.70
REMARK 3 BIN RESOLUTION RANGE LOW (A) : 2.77
REMARK 3 REFLECTION IN BIN (WORKING SET) : 1710
REMARK 3 BIN COMPLETENESS (WORKING+TEST) (%) : 99.50
REMARK 3 BIN R VALUE (WORKING SET) : 0.2800
REMARK 3 BIN FREE R VALUE SET COUNT : 88
REMARK 3 BIN FREE R VALUE : 0.3500
REMARK 3
REMARK 3 NUMBER OF NON-HYDROGEN ATOMS USED IN REFINEMENT.
REMARK 3 PROTEIN ATOMS : 5062
REMARK 3 NUCLEIC ACID ATOMS : 0
REMARK 3 HETEROGEN ATOMS : 95
REMARK 3 SOLVENT ATOMS : 87
REMARK 3
REMARK 3 B VALUES.
REMARK 3 FROM WILSON PLOT (A**2) : NULL
REMARK 3 MEAN B VALUE (OVERALL, A**2) : 66.23
REMARK 3 OVERALL ANISOTROPIC B VALUE.
REMARK 3 B11 (A**2) : 0.00000
REMARK 3 B22 (A**2) : 0.00000
REMARK 3 B33 (A**2) : 0.00000
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 OVERALL COORDINATE ERROR.
REMARK 3 ESU BASED ON R VALUE (A): 0.868
REMARK 3 ESU BASED ON FREE R VALUE (A): 0.330
REMARK 3 ESU BASED ON MAXIMUM LIKELIHOOD (A): 0.255
REMARK 3 ESU FOR B VALUES BASED ON MAXIMUM LIKELIHOOD (A**2): 25.441
REMARK 3
REMARK 3 CORRELATION COEFFICIENTS.
REMARK 3 CORRELATION COEFFICIENT FO-FC : 0.945
REMARK 3 CORRELATION COEFFICIENT FO-FC FREE : 0.909
REMARK 3
REMARK 3 RMS DEVIATIONS FROM IDEAL VALUES COUNT RMS WEIGHT
REMARK 3 BOND LENGTHS REFINED ATOMS (A): 5284 ; 0.008 ; 0.019
REMARK 3 BOND LENGTHS OTHERS (A): NULL ; NULL ; NULL
REMARK 3 BOND ANGLES REFINED ATOMS (DEGREES): 7182 ; 1.272 ; 1.965
REMARK 3 BOND ANGLES OTHERS (DEGREES): NULL ; NULL ; NULL
REMARK 3 TORSION ANGLES, PERIOD 1 (DEGREES): 664 ; 6.843 ; 5.000
REMARK 3 TORSION ANGLES, PERIOD 2 (DEGREES): 212 ;35.837 ;24.245
REMARK 3 TORSION ANGLES, PERIOD 3 (DEGREES): 794 ;15.466 ;15.000
REMARK 3 TORSION ANGLES, PERIOD 4 (DEGREES): 17 ;12.963 ;15.000
REMARK 3 CHIRAL-CENTER RESTRAINTS (A**3): 810 ; 0.080 ; 0.200
REMARK 3 GENERAL PLANES REFINED ATOMS (A): 3958 ; 0.004 ; 0.021
REMARK 3 GENERAL PLANES OTHERS (A): NULL ; NULL ; NULL
REMARK 3 NON-BONDED CONTACTS REFINED ATOMS (A): NULL ; NULL ; NULL
REMARK 3 NON-BONDED CONTACTS OTHERS (A): NULL ; NULL ; NULL
REMARK 3 NON-BONDED TORSION REFINED ATOMS (A): NULL ; NULL ; NULL
REMARK 3 NON-BONDED TORSION OTHERS (A): NULL ; NULL ; NULL
REMARK 3 H-BOND (X...Y) REFINED ATOMS (A): NULL ; NULL ; NULL
REMARK 3 H-BOND (X...Y) OTHERS (A): NULL ; NULL ; NULL
REMARK 3 POTENTIAL METAL-ION REFINED ATOMS (A): NULL ; NULL ; NULL
REMARK 3 POTENTIAL METAL-ION OTHERS (A): NULL ; NULL ; NULL
REMARK 3 SYMMETRY VDW REFINED ATOMS (A): NULL ; NULL ; NULL
REMARK 3 SYMMETRY VDW OTHERS (A): NULL ; NULL ; NULL
REMARK 3 SYMMETRY H-BOND REFINED ATOMS (A): NULL ; NULL ; NULL
REMARK 3 SYMMETRY H-BOND OTHERS (A): NULL ; NULL ; NULL
REMARK 3 SYMMETRY METAL-ION REFINED ATOMS (A): NULL ; NULL ; NULL
REMARK 3 SYMMETRY METAL-ION OTHERS (A): NULL ; NULL ; NULL
REMARK 3
REMARK 3 ISOTROPIC THERMAL FACTOR RESTRAINTS. COUNT RMS WEIGHT
REMARK 3 MAIN-CHAIN BOND REFINED ATOMS (A**2): 2668 ; 0.948 ; 4.564
REMARK 3 MAIN-CHAIN BOND OTHER ATOMS (A**2): NULL ; NULL ; NULL
REMARK 3 MAIN-CHAIN ANGLE REFINED ATOMS (A**2): 3328 ; 1.663 ; 6.845
REMARK 3 MAIN-CHAIN ANGLE OTHER ATOMS (A**2): NULL ; NULL ; NULL
REMARK 3 SIDE-CHAIN BOND REFINED ATOMS (A**2): 2616 ; 1.007 ; 4.637
REMARK 3 SIDE-CHAIN BOND OTHER ATOMS (A**2): NULL ; NULL ; NULL
REMARK 3 SIDE-CHAIN ANGLE REFINED ATOMS (A**2): NULL ; NULL ; NULL
REMARK 3 SIDE-CHAIN ANGLE OTHER ATOMS (A**2): NULL ; NULL ; NULL
REMARK 3 LONG RANGE B REFINED ATOMS (A**2): NULL ; NULL ; NULL
REMARK 3 LONG RANGE B OTHER ATOMS (A**2): NULL ; NULL ; NULL
REMARK 3
REMARK 3 ANISOTROPIC THERMAL FACTOR RESTRAINTS. COUNT RMS WEIGHT
REMARK 3 RIGID-BOND RESTRAINTS (A**2): NULL ; NULL ; NULL
REMARK 3 SPHERICITY; FREE ATOMS (A**2): NULL ; NULL ; NULL
REMARK 3 SPHERICITY; BONDED ATOMS (A**2): NULL ; NULL ; NULL
REMARK 3
REMARK 3 NCS RESTRAINTS STATISTICS
REMARK 3 NUMBER OF DIFFERENT NCS GROUPS : NULL
REMARK 3
REMARK 3 TLS DETAILS
REMARK 3 NUMBER OF TLS GROUPS : 2
REMARK 3
REMARK 3 TLS GROUP : 1
REMARK 3 NUMBER OF COMPONENTS GROUP : 10
REMARK 3 COMPONENTS C SSSEQI TO C SSSEQI
REMARK 3 RESIDUE RANGE : A 5 A 78
REMARK 3 RESIDUE RANGE : A 79 A 91
REMARK 3 RESIDUE RANGE : A 92 A 154
REMARK 3 RESIDUE RANGE : A 155 A 248
REMARK 3 RESIDUE RANGE : A 249 A 265
REMARK 3 RESIDUE RANGE : A 266 A 280
REMARK 3 RESIDUE RANGE : A 281 A 298
REMARK 3 RESIDUE RANGE : A 299 A 302
REMARK 3 RESIDUE RANGE : A 303 A 312
REMARK 3 RESIDUE RANGE : A 313 A 340
REMARK 3 ORIGIN FOR THE GROUP (A): -40.4103 3.6437 11.1455
REMARK 3 T TENSOR
REMARK 3 T11: 0.0827 T22: 0.1115
REMARK 3 T33: 0.0416 T12: -0.0288
REMARK 3 T13: 0.0174 T23: -0.0053
REMARK 3 L TENSOR
REMARK 3 L11: 3.5579 L22: 2.1718
REMARK 3 L33: 1.0379 L12: -1.7515
REMARK 3 L13: 0.5688 L23: -0.4553
REMARK 3 S TENSOR
REMARK 3 S11: 0.2323 S12: 0.3019 S13: 0.0516
REMARK 3 S21: -0.1464 S22: -0.2071 S23: -0.2396
REMARK 3 S31: -0.0300 S32: 0.3065 S33: -0.0253
REMARK 3
REMARK 3 TLS GROUP : 2
REMARK 3 NUMBER OF COMPONENTS GROUP : 10
REMARK 3 COMPONENTS C SSSEQI TO C SSSEQI
REMARK 3 RESIDUE RANGE : B 4 B 78
REMARK 3 RESIDUE RANGE : B 79 B 91
REMARK 3 RESIDUE RANGE : B 92 B 154
REMARK 3 RESIDUE RANGE : B 155 B 248
REMARK 3 RESIDUE RANGE : B 249 B 265
REMARK 3 RESIDUE RANGE : B 266 B 280
REMARK 3 RESIDUE RANGE : B 281 B 298
REMARK 3 RESIDUE RANGE : B 299 B 302
REMARK 3 RESIDUE RANGE : B 303 B 312
REMARK 3 RESIDUE RANGE : B 313 B 340
REMARK 3 ORIGIN FOR THE GROUP (A): -17.1994 -12.4726 34.0571
REMARK 3 T TENSOR
REMARK 3 T11: 0.0361 T22: 0.1440
REMARK 3 T33: 0.1382 T12: 0.0267
REMARK 3 T13: -0.0353 T23: -0.0815
REMARK 3 L TENSOR
REMARK 3 L11: 2.9321 L22: 2.9053
REMARK 3 L33: 3.0385 L12: 1.4714
REMARK 3 L13: -0.4448 L23: -0.6123
REMARK 3 S TENSOR
REMARK 3 S11: 0.0056 S12: 0.1624 S13: -0.3420
REMARK 3 S21: -0.1001 S22: 0.0340 S23: -0.2871
REMARK 3 S31: 0.2492 S32: 0.1791 S33: -0.0396
REMARK 3
REMARK 3 BULK SOLVENT MODELLING.
REMARK 3 METHOD USED : NULL
REMARK 3 PARAMETERS FOR MASK CALCULATION
REMARK 3 VDW PROBE RADIUS : 1.20
REMARK 3 ION PROBE RADIUS : 0.80
REMARK 3 SHRINKAGE RADIUS : 0.80
REMARK 3
REMARK 3 OTHER REFINEMENT REMARKS: U VALUES : WITH TLS ADDED
REMARK 4
REMARK 4 5KOQ COMPLIES WITH FORMAT V. 3.30, 13-JUL-11
REMARK 100
REMARK 100 THIS ENTRY HAS BEEN PROCESSED BY RCSB ON 06-JUL-16.
REMARK 100 THE DEPOSITION ID IS D_1000222510.
REMARK 200
REMARK 200 EXPERIMENTAL DETAILS
REMARK 200 EXPERIMENT TYPE : X-RAY DIFFRACTION
REMARK 200 DATE OF DATA COLLECTION : 28-FEB-07
REMARK 200 TEMPERATURE (KELVIN) : 100
REMARK 200 PH : 7.6
REMARK 200 NUMBER OF CRYSTALS USED : 1
REMARK 200
REMARK 200 SYNCHROTRON (Y/N) : Y
REMARK 200 RADIATION SOURCE : ALS
REMARK 200 BEAMLINE : 5.0.3
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 : SI(220)
REMARK 200 OPTICS : NULL
REMARK 200
REMARK 200 DETECTOR TYPE : CCD
REMARK 200 DETECTOR MANUFACTURER : ADSC QUANTUM 4R
REMARK 200 INTENSITY-INTEGRATION SOFTWARE : HKL-2000
REMARK 200 DATA SCALING SOFTWARE : HKL-2000
REMARK 200
REMARK 200 NUMBER OF UNIQUE REFLECTIONS : 24640
REMARK 200 RESOLUTION RANGE HIGH (A) : 2.700
REMARK 200 RESOLUTION RANGE LOW (A) : 50.000
REMARK 200 REJECTION CRITERIA (SIGMA(I)) : NULL
REMARK 200
REMARK 200 OVERALL.
REMARK 200 COMPLETENESS FOR RANGE (%) : 100.0
REMARK 200 DATA REDUNDANCY : 5.900
REMARK 200 R MERGE (I) : 0.07100
REMARK 200 R SYM (I) : NULL
REMARK 200 <I/SIGMA(I)> FOR THE DATA SET : 11.6000
REMARK 200
REMARK 200 IN THE HIGHEST RESOLUTION SHELL.
REMARK 200 HIGHEST RESOLUTION SHELL, RANGE HIGH (A) : 2.70
REMARK 200 HIGHEST RESOLUTION SHELL, RANGE LOW (A) : 2.78
REMARK 200 COMPLETENESS FOR SHELL (%) : 100.0
REMARK 200 DATA REDUNDANCY IN SHELL : 6.00
REMARK 200 R MERGE FOR SHELL (I) : 0.72100
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: MOLREP
REMARK 200 STARTING MODEL: NULL
REMARK 200
REMARK 200 REMARK: NULL
REMARK 280
REMARK 280 CRYSTAL
REMARK 280 SOLVENT CONTENT, VS (%): 59.01
REMARK 280 MATTHEWS COEFFICIENT, VM (ANGSTROMS**3/DA): 3.00
REMARK 280
REMARK 280 CRYSTALLIZATION CONDITIONS: 23% PEG600, 100 MM CITRIC ACID, PH
REMARK 280 7.6, VAPOR DIFFUSION, SITTING DROP, TEMPERATURE 293K
REMARK 290
REMARK 290 CRYSTALLOGRAPHIC SYMMETRY
REMARK 290 SYMMETRY OPERATORS FOR SPACE GROUP: P 21 3
REMARK 290
REMARK 290 SYMOP SYMMETRY
REMARK 290 NNNMMM OPERATOR
REMARK 290 1555 X,Y,Z
REMARK 290 2555 -X+1/2,-Y,Z+1/2
REMARK 290 3555 -X,Y+1/2,-Z+1/2
REMARK 290 4555 X+1/2,-Y+1/2,-Z
REMARK 290 5555 Z,X,Y
REMARK 290 6555 Z+1/2,-X+1/2,-Y
REMARK 290 7555 -Z+1/2,-X,Y+1/2
REMARK 290 8555 -Z,X+1/2,-Y+1/2
REMARK 290 9555 Y,Z,X
REMARK 290 10555 -Y,Z+1/2,-X+1/2
REMARK 290 11555 Y+1/2,-Z+1/2,-X
REMARK 290 12555 -Y+1/2,-Z,X+1/2
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 69.28100
REMARK 290 SMTRY2 2 0.000000 -1.000000 0.000000 0.00000
REMARK 290 SMTRY3 2 0.000000 0.000000 1.000000 69.28100
REMARK 290 SMTRY1 3 -1.000000 0.000000 0.000000 0.00000
REMARK 290 SMTRY2 3 0.000000 1.000000 0.000000 69.28100
REMARK 290 SMTRY3 3 0.000000 0.000000 -1.000000 69.28100
REMARK 290 SMTRY1 4 1.000000 0.000000 0.000000 69.28100
REMARK 290 SMTRY2 4 0.000000 -1.000000 0.000000 69.28100
REMARK 290 SMTRY3 4 0.000000 0.000000 -1.000000 0.00000
REMARK 290 SMTRY1 5 0.000000 0.000000 1.000000 0.00000
REMARK 290 SMTRY2 5 1.000000 0.000000 0.000000 0.00000
REMARK 290 SMTRY3 5 0.000000 1.000000 0.000000 0.00000
REMARK 290 SMTRY1 6 0.000000 0.000000 1.000000 69.28100
REMARK 290 SMTRY2 6 -1.000000 0.000000 0.000000 69.28100
REMARK 290 SMTRY3 6 0.000000 -1.000000 0.000000 0.00000
REMARK 290 SMTRY1 7 0.000000 0.000000 -1.000000 69.28100
REMARK 290 SMTRY2 7 -1.000000 0.000000 0.000000 0.00000
REMARK 290 SMTRY3 7 0.000000 1.000000 0.000000 69.28100
REMARK 290 SMTRY1 8 0.000000 0.000000 -1.000000 0.00000
REMARK 290 SMTRY2 8 1.000000 0.000000 0.000000 69.28100
REMARK 290 SMTRY3 8 0.000000 -1.000000 0.000000 69.28100
REMARK 290 SMTRY1 9 0.000000 1.000000 0.000000 0.00000
REMARK 290 SMTRY2 9 0.000000 0.000000 1.000000 0.00000
REMARK 290 SMTRY3 9 1.000000 0.000000 0.000000 0.00000
REMARK 290 SMTRY1 10 0.000000 -1.000000 0.000000 0.00000
REMARK 290 SMTRY2 10 0.000000 0.000000 1.000000 69.28100
REMARK 290 SMTRY3 10 -1.000000 0.000000 0.000000 69.28100
REMARK 290 SMTRY1 11 0.000000 1.000000 0.000000 69.28100
REMARK 290 SMTRY2 11 0.000000 0.000000 -1.000000 69.28100
REMARK 290 SMTRY3 11 -1.000000 0.000000 0.000000 0.00000
REMARK 290 SMTRY1 12 0.000000 -1.000000 0.000000 69.28100
REMARK 290 SMTRY2 12 0.000000 0.000000 -1.000000 0.00000
REMARK 290 SMTRY3 12 1.000000 0.000000 0.000000 69.28100
REMARK 290
REMARK 290 REMARK: NULL
REMARK 300
REMARK 300 BIOMOLECULE: 1, 2, 3
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 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 350
REMARK 350 BIOMOLECULE: 2
REMARK 350 AUTHOR DETERMINED BIOLOGICAL UNIT: MONOMERIC
REMARK 350 APPLY THE FOLLOWING TO CHAINS: 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
REMARK 350 BIOMOLECULE: 3
REMARK 350 SOFTWARE DETERMINED QUATERNARY STRUCTURE: HEXAMERIC
REMARK 350 SOFTWARE USED: PISA
REMARK 350 TOTAL BURIED SURFACE AREA: 16580 ANGSTROM**2
REMARK 350 SURFACE AREA OF THE COMPLEX: 70840 ANGSTROM**2
REMARK 350 CHANGE IN SOLVENT FREE ENERGY: -39.0 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 350 BIOMT1 2 0.000000 0.000000 1.000000 -69.28100
REMARK 350 BIOMT2 2 -1.000000 0.000000 0.000000 -69.28100
REMARK 350 BIOMT3 2 0.000000 -1.000000 0.000000 0.00000
REMARK 350 BIOMT1 3 0.000000 -1.000000 0.000000 -69.28100
REMARK 350 BIOMT2 3 0.000000 0.000000 -1.000000 0.00000
REMARK 350 BIOMT3 3 1.000000 0.000000 0.000000 69.28100
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 GLY A 4
REMARK 465 SER A 212
REMARK 465 TYR B 83
REMARK 465 SER B 84
REMARK 465 THR B 85
REMARK 465 GLY B 86
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 ASN A 5 CG OD1 ND2
REMARK 470 ARG A 139 CD NE CZ NH1 NH2
REMARK 470 LYS A 154 CG CD CE NZ
REMARK 470 GLN A 170 CG CD OE1 NE2
REMARK 470 GLN A 184 CG CD OE1 NE2
REMARK 470 GLN A 204 CG CD OE1 NE2
REMARK 470 LYS A 206 CG CD CE NZ
REMARK 470 LYS A 241 CG CD CE NZ
REMARK 470 GLU A 244 CG CD OE1 OE2
REMARK 470 LYS A 249 CG CD CE NZ
REMARK 470 LYS A 258 CG CD CE NZ
REMARK 470 GLU A 288 CG CD OE1 OE2
REMARK 470 LYS B 73 CG CD CE NZ
REMARK 470 LEU B 79 CG CD1 CD2
REMARK 470 ARG B 82 CG CD NE CZ NH1 NH2
REMARK 470 ARG B 139 CG CD NE CZ NH1 NH2
REMARK 470 GLN B 170 CG CD OE1 NE2
REMARK 470 LYS B 241 CG CD CE NZ
REMARK 470 LYS B 249 CG CD CE NZ
REMARK 470 LYS B 250 CG CD CE NZ
REMARK 470 PHE B 253 CG CD1 CD2 CE1 CE2 CZ
REMARK 470 LYS B 275 CG CD CE 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 ASN A 75 -65.31 -135.21
REMARK 500 ARG A 251 -169.53 -121.70
REMARK 500 GLN A 287 73.96 -69.11
REMARK 500 ALA A 299 34.61 -87.25
REMARK 500 ASN B 75 -63.52 -135.20
REMARK 500 ARG B 251 -89.87 -65.23
REMARK 500 LEU B 252 -9.96 -145.23
REMARK 500 PHE B 253 -51.12 -135.15
REMARK 500 ALA B 299 32.94 -85.77
REMARK 500
REMARK 500 REMARK: NULL
REMARK 900
REMARK 900 RELATED ENTRIES
REMARK 900 RELATED ID: 5KOS RELATED DB: PDB
REMARK 900 RELATED ID: 5KOT RELATED DB: PDB
DBREF 5KOQ A 4 340 UNP P00797 RENI_HUMAN 70 406
DBREF 5KOQ B 4 340 UNP P00797 RENI_HUMAN 70 406
SEQRES 1 A 337 GLY ASN THR THR SER SER VAL ILE LEU THR ASN TYR MET
SEQRES 2 A 337 ASP THR GLN TYR TYR GLY GLU ILE GLY ILE GLY THR PRO
SEQRES 3 A 337 PRO GLN THR PHE LYS VAL VAL PHE ASP THR GLY SER SER
SEQRES 4 A 337 ASN VAL TRP VAL PRO SER SER LYS CYS SER ARG LEU TYR
SEQRES 5 A 337 THR ALA CYS VAL TYR HIS LYS LEU PHE ASP ALA SER ASP
SEQRES 6 A 337 SER SER SER TYR LYS HIS ASN GLY THR GLU LEU THR LEU
SEQRES 7 A 337 ARG TYR SER THR GLY THR VAL SER GLY PHE LEU SER GLN
SEQRES 8 A 337 ASP ILE ILE THR VAL GLY GLY ILE THR VAL THR GLN MET
SEQRES 9 A 337 PHE GLY GLU VAL THR GLU MET PRO ALA LEU PRO PHE MET
SEQRES 10 A 337 LEU ALA GLU PHE ASP GLY VAL VAL GLY MET GLY PHE ILE
SEQRES 11 A 337 GLU GLN ALA ILE GLY ARG VAL THR PRO ILE PHE ASP ASN
SEQRES 12 A 337 ILE ILE SER GLN GLY VAL LEU LYS GLU ASP VAL PHE SER
SEQRES 13 A 337 PHE TYR TYR ASN ARG ASP SER GLU ASN SER GLN SER LEU
SEQRES 14 A 337 GLY GLY GLN ILE VAL LEU GLY GLY SER ASP PRO GLN HIS
SEQRES 15 A 337 TYR GLU GLY ASN PHE HIS TYR ILE ASN LEU ILE LYS THR
SEQRES 16 A 337 GLY VAL TRP GLN ILE GLN MET LYS GLY VAL SER VAL GLY
SEQRES 17 A 337 SER SER THR LEU LEU CYS GLU ASP GLY CYS LEU ALA LEU
SEQRES 18 A 337 VAL ASP THR GLY ALA SER TYR ILE SER GLY SER THR SER
SEQRES 19 A 337 SER ILE GLU LYS LEU MET GLU ALA LEU GLY ALA LYS LYS
SEQRES 20 A 337 ARG LEU PHE ASP TYR VAL VAL LYS CYS ASN GLU GLY PRO
SEQRES 21 A 337 THR LEU PRO ASP ILE SER PHE HIS LEU GLY GLY LYS GLU
SEQRES 22 A 337 TYR THR LEU THR SER ALA ASP TYR VAL PHE GLN GLU SER
SEQRES 23 A 337 TYR SER SER LYS LYS LEU CYS THR LEU ALA ILE HIS ALA
SEQRES 24 A 337 MET ASP ILE PRO PRO PRO THR GLY PRO THR TRP ALA LEU
SEQRES 25 A 337 GLY ALA THR PHE ILE ARG LYS PHE TYR THR GLU PHE ASP
SEQRES 26 A 337 ARG ARG ASN ASN ARG ILE GLY PHE ALA LEU ALA ARG
SEQRES 1 B 337 GLY ASN THR THR SER SER VAL ILE LEU THR ASN TYR MET
SEQRES 2 B 337 ASP THR GLN TYR TYR GLY GLU ILE GLY ILE GLY THR PRO
SEQRES 3 B 337 PRO GLN THR PHE LYS VAL VAL PHE ASP THR GLY SER SER
SEQRES 4 B 337 ASN VAL TRP VAL PRO SER SER LYS CYS SER ARG LEU TYR
SEQRES 5 B 337 THR ALA CYS VAL TYR HIS LYS LEU PHE ASP ALA SER ASP
SEQRES 6 B 337 SER SER SER TYR LYS HIS ASN GLY THR GLU LEU THR LEU
SEQRES 7 B 337 ARG TYR SER THR GLY THR VAL SER GLY PHE LEU SER GLN
SEQRES 8 B 337 ASP ILE ILE THR VAL GLY GLY ILE THR VAL THR GLN MET
SEQRES 9 B 337 PHE GLY GLU VAL THR GLU MET PRO ALA LEU PRO PHE MET
SEQRES 10 B 337 LEU ALA GLU PHE ASP GLY VAL VAL GLY MET GLY PHE ILE
SEQRES 11 B 337 GLU GLN ALA ILE GLY ARG VAL THR PRO ILE PHE ASP ASN
SEQRES 12 B 337 ILE ILE SER GLN GLY VAL LEU LYS GLU ASP VAL PHE SER
SEQRES 13 B 337 PHE TYR TYR ASN ARG ASP SER GLU ASN SER GLN SER LEU
SEQRES 14 B 337 GLY GLY GLN ILE VAL LEU GLY GLY SER ASP PRO GLN HIS
SEQRES 15 B 337 TYR GLU GLY ASN PHE HIS TYR ILE ASN LEU ILE LYS THR
SEQRES 16 B 337 GLY VAL TRP GLN ILE GLN MET LYS GLY VAL SER VAL GLY
SEQRES 17 B 337 SER SER THR LEU LEU CYS GLU ASP GLY CYS LEU ALA LEU
SEQRES 18 B 337 VAL ASP THR GLY ALA SER TYR ILE SER GLY SER THR SER
SEQRES 19 B 337 SER ILE GLU LYS LEU MET GLU ALA LEU GLY ALA LYS LYS
SEQRES 20 B 337 ARG LEU PHE ASP TYR VAL VAL LYS CYS ASN GLU GLY PRO
SEQRES 21 B 337 THR LEU PRO ASP ILE SER PHE HIS LEU GLY GLY LYS GLU
SEQRES 22 B 337 TYR THR LEU THR SER ALA ASP TYR VAL PHE GLN GLU SER
SEQRES 23 B 337 TYR SER SER LYS LYS LEU CYS THR LEU ALA ILE HIS ALA
SEQRES 24 B 337 MET ASP ILE PRO PRO PRO THR GLY PRO THR TRP ALA LEU
SEQRES 25 B 337 GLY ALA THR PHE ILE ARG LYS PHE TYR THR GLU PHE ASP
SEQRES 26 B 337 ARG ARG ASN ASN ARG ILE GLY PHE ALA LEU ALA ARG
HET NAG A 401 14
HET 6VR A 402 30
HET NAG B 401 14
HET 6VR B 402 30
HET PEG B 403 7
HETNAM NAG 2-ACETAMIDO-2-DEOXY-BETA-D-GLUCOPYRANOSE
HETNAM 6VR 2-~{TERT}-BUTYL-4-(FURAN-2-YLMETHYLAMINO)-~{N}-(2-
HETNAM 2 6VR METHYLPROPYL)-~{N}-[(3~{S})-PIPERIDIN-3-YL]PYRIMIDINE-
HETNAM 3 6VR 5-CARBOXAMIDE
HETNAM PEG DI(HYDROXYETHYL)ETHER
FORMUL 3 NAG 2(C8 H15 N O6)
FORMUL 4 6VR 2(C23 H35 N5 O2)
FORMUL 7 PEG C4 H10 O3
FORMUL 8 HOH *87(H2 O)
HELIX 1 AA1 TYR A 55 HIS A 61 1 7
HELIX 2 AA2 ASP A 65 SER A 69 5 5
HELIX 3 AA3 PRO A 115 MET A 120 1 6
HELIX 4 AA4 PHE A 132 VAL A 140 5 9
HELIX 5 AA5 PRO A 142 GLY A 151 1 10
HELIX 6 AA6 SER A 235 GLY A 247 1 13
HELIX 7 AA7 ASN A 260 LEU A 265 5 6
HELIX 8 AA8 THR A 280 VAL A 285 1 6
HELIX 9 AA9 GLY A 316 LYS A 322 1 7
HELIX 10 AB1 TYR B 55 TYR B 60 1 6
HELIX 11 AB2 ASP B 65 SER B 69 5 5
HELIX 12 AB3 PRO B 115 MET B 120 1 6
HELIX 13 AB4 PHE B 132 VAL B 140 5 9
HELIX 14 AB5 PRO B 142 GLY B 151 1 10
HELIX 15 AB6 ASP B 182 GLN B 184 5 3
HELIX 16 AB7 SER B 235 GLY B 247 1 13
HELIX 17 AB8 GLU B 261 LEU B 265 5 5
HELIX 18 AB9 THR B 280 VAL B 285 1 6
HELIX 19 AC1 GLY B 316 LYS B 322 1 7
SHEET 1 AA1 9 LYS A 73 TYR A 83 0
SHEET 2 AA1 9 GLY A 86 VAL A 99 -1 O GLN A 94 N LYS A 73
SHEET 3 AA1 9 GLN A 19 ILE A 26 -1 N GLY A 25 O THR A 98
SHEET 4 AA1 9 SER A 8 TYR A 15 -1 N TYR A 15 O GLN A 19
SHEET 5 AA1 9 GLY A 174 LEU A 178 -1 O LEU A 178 N SER A 8
SHEET 6 AA1 9 VAL A 157 TYR A 162 -1 N TYR A 161 O GLN A 175
SHEET 7 AA1 9 PHE A 323 ASP A 328 -1 O PHE A 327 N PHE A 158
SHEET 8 AA1 9 ARG A 333 ALA A 339 -1 O GLY A 335 N GLU A 326
SHEET 9 AA1 9 TYR A 186 ASN A 194 -1 N ILE A 193 O ILE A 334
SHEET 1 AA213 LYS A 73 TYR A 83 0
SHEET 2 AA213 GLY A 86 VAL A 99 -1 O GLN A 94 N LYS A 73
SHEET 3 AA213 ILE A 102 GLU A 113 -1 O VAL A 104 N ILE A 97
SHEET 4 AA213 VAL A 44 PRO A 47 1 N VAL A 44 O GLY A 109
SHEET 5 AA213 GLY A 126 GLY A 129 -1 O VAL A 127 N TRP A 45
SHEET 6 AA213 GLN A 31 ASP A 38 1 N VAL A 36 O VAL A 128
SHEET 7 AA213 GLN A 19 ILE A 26 -1 N GLY A 22 O VAL A 35
SHEET 8 AA213 SER A 8 TYR A 15 -1 N TYR A 15 O GLN A 19
SHEET 9 AA213 GLY A 174 LEU A 178 -1 O LEU A 178 N SER A 8
SHEET 10 AA213 VAL A 157 TYR A 162 -1 N TYR A 161 O GLN A 175
SHEET 11 AA213 PHE A 323 ASP A 328 -1 O PHE A 327 N PHE A 158
SHEET 12 AA213 ARG A 333 ALA A 339 -1 O GLY A 335 N GLU A 326
SHEET 13 AA213 TYR A 186 ASN A 194 -1 N ILE A 193 O ILE A 334
SHEET 1 AA3 4 THR A 214 LEU A 216 0
SHEET 2 AA3 4 GLN A 202 VAL A 210 -1 N VAL A 208 O LEU A 216
SHEET 3 AA3 4 ILE A 268 LEU A 272 -1 O HIS A 271 N GLY A 207
SHEET 4 AA3 4 LYS A 275 LEU A 279 -1 O LEU A 279 N ILE A 268
SHEET 1 AA4 6 THR A 214 LEU A 216 0
SHEET 2 AA4 6 GLN A 202 VAL A 210 -1 N VAL A 208 O LEU A 216
SHEET 3 AA4 6 CYS A 221 VAL A 225 -1 O ALA A 223 N ILE A 203
SHEET 4 AA4 6 TRP A 313 LEU A 315 1 O TRP A 313 N LEU A 224
SHEET 5 AA4 6 ILE A 232 GLY A 234 -1 N SER A 233 O ALA A 314
SHEET 6 AA4 6 ILE A 300 ALA A 302 1 O HIS A 301 N ILE A 232
SHEET 1 AA5 3 LYS A 249 LYS A 250 0
SHEET 2 AA5 3 TYR A 255 LYS A 258 -1 O VAL A 256 N LYS A 249
SHEET 3 AA5 3 LEU A 295 THR A 297 -1 O CYS A 296 N VAL A 257
SHEET 1 AA6 9 LYS B 73 LEU B 81 0
SHEET 2 AA6 9 VAL B 88 VAL B 99 -1 O LEU B 92 N GLY B 76
SHEET 3 AA6 9 GLN B 19 ILE B 26 -1 N GLY B 25 O THR B 98
SHEET 4 AA6 9 SER B 8 TYR B 15 -1 N TYR B 15 O GLN B 19
SHEET 5 AA6 9 GLY B 174 LEU B 178 -1 O LEU B 178 N SER B 8
SHEET 6 AA6 9 VAL B 157 TYR B 162 -1 N SER B 159 O VAL B 177
SHEET 7 AA6 9 PHE B 323 ASP B 328 -1 O PHE B 327 N PHE B 158
SHEET 8 AA6 9 ARG B 333 ALA B 339 -1 O GLY B 335 N GLU B 326
SHEET 9 AA6 9 TYR B 186 ASN B 194 -1 N GLU B 187 O LEU B 338
SHEET 1 AA713 LYS B 73 LEU B 81 0
SHEET 2 AA713 VAL B 88 VAL B 99 -1 O LEU B 92 N GLY B 76
SHEET 3 AA713 ILE B 102 GLU B 113 -1 O GLU B 110 N PHE B 91
SHEET 4 AA713 VAL B 44 PRO B 47 1 N VAL B 44 O GLY B 109
SHEET 5 AA713 GLY B 126 GLY B 129 -1 O VAL B 127 N TRP B 45
SHEET 6 AA713 GLN B 31 ASP B 38 1 N ASP B 38 O VAL B 128
SHEET 7 AA713 GLN B 19 ILE B 26 -1 N GLY B 22 O VAL B 35
SHEET 8 AA713 SER B 8 TYR B 15 -1 N TYR B 15 O GLN B 19
SHEET 9 AA713 GLY B 174 LEU B 178 -1 O LEU B 178 N SER B 8
SHEET 10 AA713 VAL B 157 TYR B 162 -1 N SER B 159 O VAL B 177
SHEET 11 AA713 PHE B 323 ASP B 328 -1 O PHE B 327 N PHE B 158
SHEET 12 AA713 ARG B 333 ALA B 339 -1 O GLY B 335 N GLU B 326
SHEET 13 AA713 TYR B 186 ASN B 194 -1 N GLU B 187 O LEU B 338
SHEET 1 AA8 5 GLN B 202 MET B 205 0
SHEET 2 AA8 5 CYS B 221 VAL B 225 -1 O ALA B 223 N ILE B 203
SHEET 3 AA8 5 TRP B 313 LEU B 315 1 O LEU B 315 N LEU B 224
SHEET 4 AA8 5 ILE B 232 GLY B 234 -1 N SER B 233 O ALA B 314
SHEET 5 AA8 5 ILE B 300 ALA B 302 1 O HIS B 301 N ILE B 232
SHEET 1 AA9 4 SER B 213 LEU B 216 0
SHEET 2 AA9 4 VAL B 208 VAL B 210 -1 N VAL B 208 O LEU B 216
SHEET 3 AA9 4 ILE B 268 LEU B 272 -1 O SER B 269 N SER B 209
SHEET 4 AA9 4 LYS B 275 LEU B 279 -1 O LEU B 279 N ILE B 268
SHEET 1 AB1 3 LYS B 249 LYS B 250 0
SHEET 2 AB1 3 TYR B 255 LYS B 258 -1 O VAL B 256 N LYS B 249
SHEET 3 AB1 3 LEU B 295 THR B 297 -1 O CYS B 296 N VAL B 257
SSBOND 1 CYS A 51 CYS A 58 1555 1555 2.03
SSBOND 2 CYS A 217 CYS A 221 1555 1555 2.03
SSBOND 3 CYS A 259 CYS A 296 1555 1555 2.03
SSBOND 4 CYS B 51 CYS B 58 1555 1555 2.03
SSBOND 5 CYS B 217 CYS B 221 1555 1555 2.02
SSBOND 6 CYS B 259 CYS B 296 1555 1555 2.03
LINK ND2 ASN A 75 C1 NAG A 401 1555 1555 1.44
LINK ND2 ASN B 75 C1 NAG B 401 1555 1555 1.45
CISPEP 1 THR A 28 PRO A 29 0 -4.53
CISPEP 2 LEU A 117 PRO A 118 0 10.30
CISPEP 3 PRO A 307 PRO A 308 0 2.43
CISPEP 4 GLY A 310 PRO A 311 0 -3.09
CISPEP 5 THR B 28 PRO B 29 0 -0.15
CISPEP 6 LEU B 117 PRO B 118 0 6.82
CISPEP 7 PRO B 307 PRO B 308 0 0.48
CISPEP 8 GLY B 310 PRO B 311 0 3.76
CRYST1 138.562 138.562 138.562 90.00 90.00 90.00 P 21 3 24
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 0.007217 0.000000 0.000000 0.00000
SCALE2 0.000000 0.007217 0.000000 0.00000
SCALE3 0.000000 0.000000 0.007217 0.00000
(ATOM LINES ARE NOT SHOWN.)
END