HEADER HYDROLASE 22-AUG-06 2I4Q
TITLE HUMAN RENIN/PF02342674 COMPLEX
COMPND MOL_ID: 1;
COMPND 2 MOLECULE: RENIN;
COMPND 3 CHAIN: A, B;
COMPND 4 SYNONYM: ANGIOTENSINOGENASE;
COMPND 5 EC: 3.4.23.15;
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 GENE: REN;
SOURCE 6 EXPRESSION_SYSTEM: ESCHERICHIA COLI;
SOURCE 7 EXPRESSION_SYSTEM_TAXID: 562
KEYWDS RENIN INHIBITOR, PROTEIN-LIGAND COMPLEX, HYDROLASE
EXPDTA X-RAY DIFFRACTION
AUTHOR D.D.HOLSWORTH,M.JALAIE,E.ZHANG,P.MCCONNELL,I.MOCHALKIN,
AUTHOR 2 B.C.FINZEL
REVDAT 3 02-MAR-10 2I4Q 1 JRNL
REVDAT 2 24-FEB-09 2I4Q 1 VERSN
REVDAT 1 24-OCT-06 2I4Q 0
JRNL AUTH N.A.POWELL,F.L.CISKE,C.CAI,D.D.HOLSWORTH,K.MENNEN,
JRNL AUTH 2 C.A.VAN HUIS,M.JALAIE,J.DAY,M.MASTRONARDI,
JRNL AUTH 3 P.MCCONNELL,I.MOCHALKIN,E.ZHANG,M.J.RYAN,J.BRYANT,
JRNL AUTH 4 W.COLLARD,S.FERREIRA,C.GU,R.COLLINS,J.J.EDMUNDS
JRNL TITL RATIONAL DESIGN OF
JRNL TITL 2 6-(2,4-DIAMINOPYRIMIDINYL)-1,4-BENZOXAZIN-3-ONES AS
JRNL TITL 3 SMALL MOLECULE RENIN INHIBITORS.
JRNL REF BIOORG.MED.CHEM. V. 15 5912 2007
JRNL REFN ISSN 0968-0896
JRNL PMID 17574423
JRNL DOI 10.1016/J.BMC.2007.05.069
REMARK 2
REMARK 2 RESOLUTION. 2.30 ANGSTROMS.
REMARK 3
REMARK 3 REFINEMENT.
REMARK 3 PROGRAM : REFMAC 5.1.24
REMARK 3 AUTHORS : MURSHUDOV,VAGIN,DODSON
REMARK 3
REMARK 3 REFINEMENT TARGET : MAXIMUM LIKELIHOOD
REMARK 3
REMARK 3 DATA USED IN REFINEMENT.
REMARK 3 RESOLUTION RANGE HIGH (ANGSTROMS) : 2.30
REMARK 3 RESOLUTION RANGE LOW (ANGSTROMS) : 35.00
REMARK 3 DATA CUTOFF (SIGMA(F)) : 0.000
REMARK 3 COMPLETENESS FOR RANGE (%) : 88.8
REMARK 3 NUMBER OF REFLECTIONS : 37709
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) : 0.230
REMARK 3 R VALUE (WORKING SET) : 0.229
REMARK 3 FREE R VALUE : 0.261
REMARK 3 FREE R VALUE TEST SET SIZE (%) : 5.100
REMARK 3 FREE R VALUE TEST SET COUNT : 1919
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) : 2.30
REMARK 3 BIN RESOLUTION RANGE LOW (A) : 2.36
REMARK 3 REFLECTION IN BIN (WORKING SET) : 2771
REMARK 3 BIN COMPLETENESS (WORKING+TEST) (%) : NULL
REMARK 3 BIN R VALUE (WORKING SET) : 0.3380
REMARK 3 BIN FREE R VALUE SET COUNT : 160
REMARK 3 BIN FREE R VALUE : 0.3840
REMARK 3
REMARK 3 NUMBER OF NON-HYDROGEN ATOMS USED IN REFINEMENT.
REMARK 3 PROTEIN ATOMS : 5184
REMARK 3 NUCLEIC ACID ATOMS : 0
REMARK 3 HETEROGEN ATOMS : 70
REMARK 3 SOLVENT ATOMS : 190
REMARK 3
REMARK 3 B VALUES.
REMARK 3 FROM WILSON PLOT (A**2) : NULL
REMARK 3 MEAN B VALUE (OVERALL, A**2) : 42.00
REMARK 3 OVERALL ANISOTROPIC B VALUE.
REMARK 3 B11 (A**2) : NULL
REMARK 3 B22 (A**2) : NULL
REMARK 3 B33 (A**2) : NULL
REMARK 3 B12 (A**2) : NULL
REMARK 3 B13 (A**2) : NULL
REMARK 3 B23 (A**2) : NULL
REMARK 3
REMARK 3 ESTIMATED OVERALL COORDINATE ERROR.
REMARK 3 ESU BASED ON R VALUE (A): 0.347
REMARK 3 ESU BASED ON FREE R VALUE (A): 0.248
REMARK 3 ESU BASED ON MAXIMUM LIKELIHOOD (A): 0.169
REMARK 3 ESU FOR B VALUES BASED ON MAXIMUM LIKELIHOOD (A**2): 6.948
REMARK 3
REMARK 3 CORRELATION COEFFICIENTS.
REMARK 3 CORRELATION COEFFICIENT FO-FC : 0.941
REMARK 3 CORRELATION COEFFICIENT FO-FC FREE : 0.923
REMARK 3
REMARK 3 RMS DEVIATIONS FROM IDEAL VALUES COUNT RMS WEIGHT
REMARK 3 BOND LENGTHS REFINED ATOMS (A): 5386 ; 0.007 ; 0.021
REMARK 3 BOND LENGTHS OTHERS (A): 4732 ; 0.002 ; 0.020
REMARK 3 BOND ANGLES REFINED ATOMS (DEGREES): 7320 ; 1.080 ; 1.966
REMARK 3 BOND ANGLES OTHERS (DEGREES): 11024 ; 0.718 ; 3.000
REMARK 3 TORSION ANGLES, PERIOD 1 (DEGREES): 670 ; 6.581 ; 5.000
REMARK 3 TORSION ANGLES, PERIOD 2 (DEGREES): NULL ; NULL ; NULL
REMARK 3 TORSION ANGLES, PERIOD 3 (DEGREES): NULL ; NULL ; NULL
REMARK 3 TORSION ANGLES, PERIOD 4 (DEGREES): NULL ; NULL ; NULL
REMARK 3 CHIRAL-CENTER RESTRAINTS (A**3): 808 ; 0.064 ; 0.200
REMARK 3 GENERAL PLANES REFINED ATOMS (A): 6012 ; 0.003 ; 0.020
REMARK 3 GENERAL PLANES OTHERS (A): 1120 ; 0.002 ; 0.020
REMARK 3 NON-BONDED CONTACTS REFINED ATOMS (A): 899 ; 0.171 ; 0.200
REMARK 3 NON-BONDED CONTACTS OTHERS (A): 5375 ; 0.214 ; 0.200
REMARK 3 NON-BONDED TORSION REFINED ATOMS (A): NULL ; NULL ; NULL
REMARK 3 NON-BONDED TORSION OTHERS (A): 3281 ; 0.080 ; 0.200
REMARK 3 H-BOND (X...Y) REFINED ATOMS (A): 162 ; 0.134 ; 0.200
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): 18 ; 0.212 ; 0.200
REMARK 3 SYMMETRY VDW OTHERS (A): 100 ; 0.253 ; 0.200
REMARK 3 SYMMETRY H-BOND REFINED ATOMS (A): 15 ; 0.142 ; 0.200
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): 3316 ; 0.828 ; 2.500
REMARK 3 MAIN-CHAIN BOND OTHER ATOMS (A**2): NULL ; NULL ; NULL
REMARK 3 MAIN-CHAIN ANGLE REFINED ATOMS (A**2): 5364 ; 1.458 ; 3.500
REMARK 3 SIDE-CHAIN BOND REFINED ATOMS (A**2): 2070 ; 0.610 ; 2.500
REMARK 3 SIDE-CHAIN ANGLE REFINED ATOMS (A**2): 1956 ; 1.055 ; 3.500
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 : NULL
REMARK 3
REMARK 3 BULK SOLVENT MODELLING.
REMARK 3 METHOD USED : BABINET MODEL WITH MASK
REMARK 3 PARAMETERS FOR MASK CALCULATION
REMARK 3 VDW PROBE RADIUS : 1.40
REMARK 3 ION PROBE RADIUS : 0.80
REMARK 3 SHRINKAGE RADIUS : 0.80
REMARK 3
REMARK 3 OTHER REFINEMENT REMARKS: HYDROGENS HAVE BEEN ADDED IN THE
REMARK 3 RIDING POSITIONS
REMARK 4
REMARK 4 2I4Q COMPLIES WITH FORMAT V. 3.15, 01-DEC-08
REMARK 100
REMARK 100 THIS ENTRY HAS BEEN PROCESSED BY RCSB ON 23-AUG-06.
REMARK 100 THE RCSB ID CODE IS RCSB039134.
REMARK 200
REMARK 200 EXPERIMENTAL DETAILS
REMARK 200 EXPERIMENT TYPE : X-RAY DIFFRACTION
REMARK 200 DATE OF DATA COLLECTION : 11-JUN-04
REMARK 200 TEMPERATURE (KELVIN) : 170
REMARK 200 PH : NULL
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) : 1.000
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 : HKL-2000
REMARK 200 DATA SCALING SOFTWARE : HKL-2000
REMARK 200
REMARK 200 NUMBER OF UNIQUE REFLECTIONS : 37838
REMARK 200 RESOLUTION RANGE HIGH (A) : 2.300
REMARK 200 RESOLUTION RANGE LOW (A) : 35.000
REMARK 200 REJECTION CRITERIA (SIGMA(I)) : 0.000
REMARK 200
REMARK 200 OVERALL.
REMARK 200 COMPLETENESS FOR RANGE (%) : 89.1
REMARK 200 DATA REDUNDANCY : 2.630
REMARK 200 R MERGE (I) : 0.05100
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) : 2.30
REMARK 200 HIGHEST RESOLUTION SHELL, RANGE LOW (A) : 2.38
REMARK 200 COMPLETENESS FOR SHELL (%) : 95.2
REMARK 200 DATA REDUNDANCY IN SHELL : NULL
REMARK 200 R MERGE FOR SHELL (I) : 0.28900
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: CNS
REMARK 200 STARTING MODEL: NULL
REMARK 200
REMARK 200 REMARK: NULL
REMARK 280
REMARK 280 CRYSTAL
REMARK 280 SOLVENT CONTENT, VS (%): 61.88
REMARK 280 MATTHEWS COEFFICIENT, VM (ANGSTROMS**3/DA): 3.23
REMARK 280
REMARK 280 CRYSTALLIZATION CONDITIONS: NULL
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 70.94900
REMARK 290 SMTRY2 2 0.000000 -1.000000 0.000000 0.00000
REMARK 290 SMTRY3 2 0.000000 0.000000 1.000000 70.94900
REMARK 290 SMTRY1 3 -1.000000 0.000000 0.000000 0.00000
REMARK 290 SMTRY2 3 0.000000 1.000000 0.000000 70.94900
REMARK 290 SMTRY3 3 0.000000 0.000000 -1.000000 70.94900
REMARK 290 SMTRY1 4 1.000000 0.000000 0.000000 70.94900
REMARK 290 SMTRY2 4 0.000000 -1.000000 0.000000 70.94900
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 70.94900
REMARK 290 SMTRY2 6 -1.000000 0.000000 0.000000 70.94900
REMARK 290 SMTRY3 6 0.000000 -1.000000 0.000000 0.00000
REMARK 290 SMTRY1 7 0.000000 0.000000 -1.000000 70.94900
REMARK 290 SMTRY2 7 -1.000000 0.000000 0.000000 0.00000
REMARK 290 SMTRY3 7 0.000000 1.000000 0.000000 70.94900
REMARK 290 SMTRY1 8 0.000000 0.000000 -1.000000 0.00000
REMARK 290 SMTRY2 8 1.000000 0.000000 0.000000 70.94900
REMARK 290 SMTRY3 8 0.000000 -1.000000 0.000000 70.94900
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 70.94900
REMARK 290 SMTRY3 10 -1.000000 0.000000 0.000000 70.94900
REMARK 290 SMTRY1 11 0.000000 1.000000 0.000000 70.94900
REMARK 290 SMTRY2 11 0.000000 0.000000 -1.000000 70.94900
REMARK 290 SMTRY3 11 -1.000000 0.000000 0.000000 0.00000
REMARK 290 SMTRY1 12 0.000000 -1.000000 0.000000 70.94900
REMARK 290 SMTRY2 12 0.000000 0.000000 -1.000000 0.00000
REMARK 290 SMTRY3 12 1.000000 0.000000 0.000000 70.94900
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 300 REMARK: THIS ENTRY CONTAINS A DIMER IN THE ASYMMETRIC UNIT THAT
REMARK 300 CONSTITUTES A BIOLOGICALLY ACTIVE SPECIES
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: DIMERIC
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 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 ARG A 335 O
REMARK 470 ARG B 335 O
REMARK 500
REMARK 500 GEOMETRY AND STEREOCHEMISTRY
REMARK 500 SUBTOPIC: CLOSE CONTACTS IN SAME ASYMMETRIC UNIT
REMARK 500
REMARK 500 THE FOLLOWING ATOMS ARE IN CLOSE CONTACT.
REMARK 500
REMARK 500 ATM1 RES C SSEQI ATM2 RES C SSEQI DISTANCE
REMARK 500 O ASN B 70 O LEU B 87 2.11
REMARK 500
REMARK 500 REMARK: NULL
REMARK 500
REMARK 500 GEOMETRY AND STEREOCHEMISTRY
REMARK 500 SUBTOPIC: COVALENT BOND ANGLES
REMARK 500
REMARK 500 THE STEREOCHEMICAL PARAMETERS OF THE FOLLOWING RESIDUES
REMARK 500 HAVE VALUES WHICH DEVIATE FROM EXPECTED VALUES BY MORE
REMARK 500 THAN 6*RMSD (M=MODEL NUMBER; RES=RESIDUE NAME; C=CHAIN
REMARK 500 IDENTIFIER; SSEQ=SEQUENCE NUMBER; I=INSERTION CODE).
REMARK 500
REMARK 500 STANDARD TABLE:
REMARK 500 FORMAT: (10X,I3,1X,A3,1X,A1,I4,A1,3(1X,A4,2X),12X,F5.1)
REMARK 500
REMARK 500 EXPECTED VALUES PROTEIN: ENGH AND HUBER, 1999
REMARK 500 EXPECTED VALUES NUCLEIC ACID: CLOWNEY ET AL 1996
REMARK 500
REMARK 500 M RES CSSEQI ATM1 ATM2 ATM3
REMARK 500 ASP A 12 CB - CG - OD2 ANGL. DEV. = 6.0 DEGREES
REMARK 500 ASP A 160 CB - CG - OD2 ANGL. DEV. = 5.8 DEGREES
REMARK 500 ASP A 323 CB - CG - OD2 ANGL. DEV. = 5.7 DEGREES
REMARK 500 ASP B 160 CB - CG - OD2 ANGL. DEV. = 5.6 DEGREES
REMARK 500 ASP B 323 CB - CG - OD2 ANGL. DEV. = 5.8 DEGREES
REMARK 500
REMARK 500 REMARK: NULL
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 70 -62.18 -133.70
REMARK 500 SER A 207 53.64 -98.77
REMARK 500 SER A 208 141.19 -172.29
REMARK 500 ASP A 214 -14.67 77.14
REMARK 500 ALA A 294 34.65 -83.71
REMARK 500 ASN B 70 91.19 -172.27
REMARK 500 MET B 109 89.08 -152.64
REMARK 500 GLN B 165 49.58 -106.91
REMARK 500 ARG B 246 -74.30 -59.85
REMARK 500 LEU B 247 -55.63 -148.39
REMARK 500 ALA B 294 33.08 -86.50
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 A 340 DISTANCE = 6.18 ANGSTROMS
REMARK 525 HOH B 349 DISTANCE = 7.42 ANGSTROMS
REMARK 525 HOH A 392 DISTANCE = 7.78 ANGSTROMS
REMARK 525 HOH A 400 DISTANCE = 5.48 ANGSTROMS
REMARK 525 HOH B 404 DISTANCE = 6.15 ANGSTROMS
REMARK 525 HOH A 405 DISTANCE = 5.60 ANGSTROMS
REMARK 525 HOH B 414 DISTANCE = 5.70 ANGSTROMS
REMARK 800
REMARK 800 SITE
REMARK 800 SITE_IDENTIFIER: AC1
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: BINDING SITE FOR RESIDUE UA4 B 336
REMARK 800
REMARK 800 SITE_IDENTIFIER: AC2
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: BINDING SITE FOR RESIDUE UA4 A 336
REMARK 900
REMARK 900 RELATED ENTRIES
REMARK 900 RELATED ID: 2G24 RELATED DB: PDB
REMARK 900 KETOPIPERAZINE-BASED RENIN INHIBITORS: OPTIMIZATION OF THE
REMARK 900 "C" RING
REMARK 900 RELATED ID: 2G21 RELATED DB: PDB
REMARK 900 KETOPIPERAZINE-BASED RENIN INHIBITORS: OPTIMIZATION OF THE
REMARK 900 "C" RING
REMARK 900 RELATED ID: 2G1S RELATED DB: PDB
REMARK 900 KETOPIPERAZINE-BASED RENIN INHIBITORS: OPTIMIZATION OF THE
REMARK 900 C RING
DBREF 2I4Q A 2 335 UNP P00797 RENI_HUMAN 71 406
DBREF 2I4Q B 2 335 UNP P00797 RENI_HUMAN 71 406
SEQADV 2I4Q ASN A 0 UNP P00797 CLONING ARTIFACT
SEQADV 2I4Q THR A 1 UNP P00797 CLONING ARTIFACT
SEQADV 2I4Q ASN B 0 UNP P00797 CLONING ARTIFACT
SEQADV 2I4Q THR B 1 UNP P00797 CLONING ARTIFACT
SEQRES 1 A 336 ASN THR THR SER SER VAL ILE LEU THR ASN TYR MET ASP
SEQRES 2 A 336 THR GLN TYR TYR GLY GLU ILE GLY ILE GLY THR PRO PRO
SEQRES 3 A 336 GLN THR PHE LYS VAL VAL PHE ASP THR GLY SER SER ASN
SEQRES 4 A 336 VAL TRP VAL PRO SER SER LYS CYS SER ARG LEU TYR THR
SEQRES 5 A 336 ALA CYS VAL TYR HIS LYS LEU PHE ASP ALA SER ASP SER
SEQRES 6 A 336 SER SER TYR LYS HIS ASN GLY THR GLU LEU THR LEU ARG
SEQRES 7 A 336 TYR SER THR GLY THR VAL SER GLY PHE LEU SER GLN ASP
SEQRES 8 A 336 ILE ILE THR VAL GLY GLY ILE THR VAL THR GLN MET PHE
SEQRES 9 A 336 GLY GLU VAL THR GLU MET PRO ALA LEU PRO PHE MET LEU
SEQRES 10 A 336 ALA GLU PHE ASP GLY VAL VAL GLY MET GLY PHE ILE GLU
SEQRES 11 A 336 GLN ALA ILE GLY ARG VAL THR PRO ILE PHE ASP ASN ILE
SEQRES 12 A 336 ILE SER GLN GLY VAL LEU LYS GLU ASP VAL PHE SER PHE
SEQRES 13 A 336 TYR TYR ASN ARG ASP SER GLU ASN SER GLN SER LEU GLY
SEQRES 14 A 336 GLY GLN ILE VAL LEU GLY GLY SER ASP PRO GLN HIS TYR
SEQRES 15 A 336 GLU GLY ASN PHE HIS TYR ILE ASN LEU ILE LYS THR GLY
SEQRES 16 A 336 VAL TRP GLN ILE GLN MET LYS GLY VAL SER VAL GLY SER
SEQRES 17 A 336 SER THR LEU LEU CYS GLU ASP GLY CYS LEU ALA LEU VAL
SEQRES 18 A 336 ASP THR GLY ALA SER TYR ILE SER GLY SER THR SER SER
SEQRES 19 A 336 ILE GLU LYS LEU MET GLU ALA LEU GLY ALA LYS LYS ARG
SEQRES 20 A 336 LEU PHE ASP TYR VAL VAL LYS CYS ASN GLU GLY PRO THR
SEQRES 21 A 336 LEU PRO ASP ILE SER PHE HIS LEU GLY GLY LYS GLU TYR
SEQRES 22 A 336 THR LEU THR SER ALA ASP TYR VAL PHE GLN GLU SER TYR
SEQRES 23 A 336 SER SER LYS LYS LEU CYS THR LEU ALA ILE HIS ALA MET
SEQRES 24 A 336 ASP ILE PRO PRO PRO THR GLY PRO THR TRP ALA LEU GLY
SEQRES 25 A 336 ALA THR PHE ILE ARG LYS PHE TYR THR GLU PHE ASP ARG
SEQRES 26 A 336 ARG ASN ASN ARG ILE GLY PHE ALA LEU ALA ARG
SEQRES 1 B 336 ASN THR THR SER SER VAL ILE LEU THR ASN TYR MET ASP
SEQRES 2 B 336 THR GLN TYR TYR GLY GLU ILE GLY ILE GLY THR PRO PRO
SEQRES 3 B 336 GLN THR PHE LYS VAL VAL PHE ASP THR GLY SER SER ASN
SEQRES 4 B 336 VAL TRP VAL PRO SER SER LYS CYS SER ARG LEU TYR THR
SEQRES 5 B 336 ALA CYS VAL TYR HIS LYS LEU PHE ASP ALA SER ASP SER
SEQRES 6 B 336 SER SER TYR LYS HIS ASN GLY THR GLU LEU THR LEU ARG
SEQRES 7 B 336 TYR SER THR GLY THR VAL SER GLY PHE LEU SER GLN ASP
SEQRES 8 B 336 ILE ILE THR VAL GLY GLY ILE THR VAL THR GLN MET PHE
SEQRES 9 B 336 GLY GLU VAL THR GLU MET PRO ALA LEU PRO PHE MET LEU
SEQRES 10 B 336 ALA GLU PHE ASP GLY VAL VAL GLY MET GLY PHE ILE GLU
SEQRES 11 B 336 GLN ALA ILE GLY ARG VAL THR PRO ILE PHE ASP ASN ILE
SEQRES 12 B 336 ILE SER GLN GLY VAL LEU LYS GLU ASP VAL PHE SER PHE
SEQRES 13 B 336 TYR TYR ASN ARG ASP SER GLU ASN SER GLN SER LEU GLY
SEQRES 14 B 336 GLY GLN ILE VAL LEU GLY GLY SER ASP PRO GLN HIS TYR
SEQRES 15 B 336 GLU GLY ASN PHE HIS TYR ILE ASN LEU ILE LYS THR GLY
SEQRES 16 B 336 VAL TRP GLN ILE GLN MET LYS GLY VAL SER VAL GLY SER
SEQRES 17 B 336 SER THR LEU LEU CYS GLU ASP GLY CYS LEU ALA LEU VAL
SEQRES 18 B 336 ASP THR GLY ALA SER TYR ILE SER GLY SER THR SER SER
SEQRES 19 B 336 ILE GLU LYS LEU MET GLU ALA LEU GLY ALA LYS LYS ARG
SEQRES 20 B 336 LEU PHE ASP TYR VAL VAL LYS CYS ASN GLU GLY PRO THR
SEQRES 21 B 336 LEU PRO ASP ILE SER PHE HIS LEU GLY GLY LYS GLU TYR
SEQRES 22 B 336 THR LEU THR SER ALA ASP TYR VAL PHE GLN GLU SER TYR
SEQRES 23 B 336 SER SER LYS LYS LEU CYS THR LEU ALA ILE HIS ALA MET
SEQRES 24 B 336 ASP ILE PRO PRO PRO THR GLY PRO THR TRP ALA LEU GLY
SEQRES 25 B 336 ALA THR PHE ILE ARG LYS PHE TYR THR GLU PHE ASP ARG
SEQRES 26 B 336 ARG ASN ASN ARG ILE GLY PHE ALA LEU ALA ARG
HET UA4 B 336 35
HET UA4 A 336 35
HETNAM UA4 (2S)-6-(2,4-DIAMINO-6-ETHYLPYRIMIDIN-5-YL)-2-(3,5-
HETNAM 2 UA4 DIFLUOROPHENYL)-4-(3-METHOXYPROPYL)-2-METHYL-2H-1,4-
HETNAM 3 UA4 BENZOXAZIN-3(4H)-ONE
FORMUL 3 UA4 2(C25 H27 F2 N5 O3)
FORMUL 5 HOH *190(H2 O)
HELIX 1 1 TYR A 50 TYR A 55 1 6
HELIX 2 2 ASP A 60 SER A 64 5 5
HELIX 3 3 PRO A 110 MET A 115 1 6
HELIX 4 4 PHE A 127 VAL A 135 5 9
HELIX 5 5 PRO A 137 SER A 144 1 8
HELIX 6 6 ASP A 177 GLN A 179 5 3
HELIX 7 7 SER A 230 GLY A 242 1 13
HELIX 8 8 ASN A 255 LEU A 260 5 6
HELIX 9 9 THR A 275 VAL A 280 1 6
HELIX 10 10 GLY A 311 LYS A 317 1 7
HELIX 11 11 TYR B 50 TYR B 55 1 6
HELIX 12 12 ASP B 60 SER B 64 5 5
HELIX 13 13 PRO B 110 MET B 115 1 6
HELIX 14 14 PHE B 127 VAL B 135 5 9
HELIX 15 15 PRO B 137 GLN B 145 1 9
HELIX 16 16 ASP B 177 TYR B 181 5 5
HELIX 17 17 SER B 230 GLY B 242 1 13
HELIX 18 18 ASN B 255 LEU B 260 5 6
HELIX 19 19 THR B 275 VAL B 280 1 6
HELIX 20 20 GLY B 311 LYS B 317 1 7
SHEET 1 A 9 LYS A 68 TYR A 78 0
SHEET 2 A 9 GLY A 81 VAL A 94 -1 O GLN A 89 N LYS A 68
SHEET 3 A 9 GLN A 14 ILE A 21 -1 N GLY A 20 O THR A 93
SHEET 4 A 9 SER A 3 TYR A 10 -1 N THR A 8 O TYR A 16
SHEET 5 A 9 GLY A 169 LEU A 173 -1 O ILE A 171 N VAL A 5
SHEET 6 A 9 VAL A 152 TYR A 157 -1 N TYR A 156 O GLN A 170
SHEET 7 A 9 PHE A 318 ASP A 323 -1 O PHE A 322 N PHE A 153
SHEET 8 A 9 ARG A 328 ALA A 334 -1 O GLY A 330 N GLU A 321
SHEET 9 A 9 TYR A 181 ASN A 189 -1 N ILE A 188 O ILE A 329
SHEET 1 B13 LYS A 68 TYR A 78 0
SHEET 2 B13 GLY A 81 VAL A 94 -1 O GLN A 89 N LYS A 68
SHEET 3 B13 ILE A 97 GLU A 108 -1 O GLU A 105 N PHE A 86
SHEET 4 B13 VAL A 39 PRO A 42 1 N VAL A 39 O GLY A 104
SHEET 5 B13 GLY A 121 GLY A 124 -1 O VAL A 122 N TRP A 40
SHEET 6 B13 GLN A 26 ASP A 33 1 N VAL A 31 O VAL A 123
SHEET 7 B13 GLN A 14 ILE A 21 -1 N GLY A 17 O VAL A 30
SHEET 8 B13 SER A 3 TYR A 10 -1 N THR A 8 O TYR A 16
SHEET 9 B13 GLY A 169 LEU A 173 -1 O ILE A 171 N VAL A 5
SHEET 10 B13 VAL A 152 TYR A 157 -1 N TYR A 156 O GLN A 170
SHEET 11 B13 PHE A 318 ASP A 323 -1 O PHE A 322 N PHE A 153
SHEET 12 B13 ARG A 328 ALA A 334 -1 O GLY A 330 N GLU A 321
SHEET 13 B13 TYR A 181 ASN A 189 -1 N ILE A 188 O ILE A 329
SHEET 1 C 5 GLN A 197 MET A 200 0
SHEET 2 C 5 CYS A 216 VAL A 220 -1 O ALA A 218 N ILE A 198
SHEET 3 C 5 TRP A 308 LEU A 310 1 O LEU A 310 N LEU A 219
SHEET 4 C 5 ILE A 227 GLY A 229 -1 N SER A 228 O ALA A 309
SHEET 5 C 5 ILE A 295 ALA A 297 1 O HIS A 296 N ILE A 227
SHEET 1 D 3 GLY A 202 VAL A 205 0
SHEET 2 D 3 ILE A 263 LEU A 267 -1 O HIS A 266 N GLY A 202
SHEET 3 D 3 LYS A 270 LEU A 274 -1 O LEU A 274 N ILE A 263
SHEET 1 E 3 LYS A 244 LYS A 245 0
SHEET 2 E 3 TYR A 250 LYS A 253 -1 O VAL A 251 N LYS A 244
SHEET 3 E 3 LEU A 290 THR A 292 -1 O CYS A 291 N VAL A 252
SHEET 1 F 9 LYS B 68 ARG B 77 0
SHEET 2 F 9 THR B 82 VAL B 94 -1 O VAL B 83 N LEU B 76
SHEET 3 F 9 GLN B 14 ILE B 21 -1 N GLY B 20 O THR B 93
SHEET 4 F 9 SER B 3 TYR B 10 -1 N THR B 8 O TYR B 16
SHEET 5 F 9 GLY B 169 LEU B 173 -1 O LEU B 173 N SER B 3
SHEET 6 F 9 VAL B 152 TYR B 157 -1 N TYR B 156 O GLN B 170
SHEET 7 F 9 PHE B 318 ASP B 323 -1 O PHE B 322 N PHE B 153
SHEET 8 F 9 ARG B 328 LEU B 333 -1 O GLY B 330 N GLU B 321
SHEET 9 F 9 HIS B 186 ASN B 189 -1 N ILE B 188 O ILE B 329
SHEET 1 G13 LYS B 68 ARG B 77 0
SHEET 2 G13 THR B 82 VAL B 94 -1 O VAL B 83 N LEU B 76
SHEET 3 G13 ILE B 97 GLU B 108 -1 O GLU B 105 N PHE B 86
SHEET 4 G13 VAL B 39 PRO B 42 1 N VAL B 41 O GLY B 104
SHEET 5 G13 GLY B 121 GLY B 124 -1 O VAL B 122 N TRP B 40
SHEET 6 G13 GLN B 26 ASP B 33 1 N VAL B 31 O VAL B 123
SHEET 7 G13 GLN B 14 ILE B 21 -1 N GLY B 17 O VAL B 30
SHEET 8 G13 SER B 3 TYR B 10 -1 N THR B 8 O TYR B 16
SHEET 9 G13 GLY B 169 LEU B 173 -1 O LEU B 173 N SER B 3
SHEET 10 G13 VAL B 152 TYR B 157 -1 N TYR B 156 O GLN B 170
SHEET 11 G13 PHE B 318 ASP B 323 -1 O PHE B 322 N PHE B 153
SHEET 12 G13 ARG B 328 LEU B 333 -1 O GLY B 330 N GLU B 321
SHEET 13 G13 HIS B 186 ASN B 189 -1 N ILE B 188 O ILE B 329
SHEET 1 H 5 GLN B 197 MET B 200 0
SHEET 2 H 5 CYS B 216 VAL B 220 -1 O ALA B 218 N ILE B 198
SHEET 3 H 5 TRP B 308 LEU B 310 1 O LEU B 310 N LEU B 219
SHEET 4 H 5 ILE B 227 GLY B 229 -1 N SER B 228 O ALA B 309
SHEET 5 H 5 ILE B 295 ALA B 297 1 O HIS B 296 N ILE B 227
SHEET 1 I 3 VAL B 203 VAL B 205 0
SHEET 2 I 3 ILE B 263 LEU B 267 -1 O SER B 264 N SER B 204
SHEET 3 I 3 LYS B 270 LEU B 274 -1 O LEU B 274 N ILE B 263
SHEET 1 J 3 LYS B 244 LYS B 245 0
SHEET 2 J 3 TYR B 250 LYS B 253 -1 O VAL B 251 N LYS B 244
SHEET 3 J 3 LEU B 290 THR B 292 -1 O CYS B 291 N VAL B 252
SSBOND 1 CYS A 46 CYS A 53 1555 1555 2.02
SSBOND 2 CYS A 212 CYS A 216 1555 1555 2.04
SSBOND 3 CYS A 254 CYS A 291 1555 1555 2.04
SSBOND 4 CYS B 46 CYS B 53 1555 1555 2.03
SSBOND 5 CYS B 212 CYS B 216 1555 1555 2.04
SSBOND 6 CYS B 254 CYS B 291 1555 1555 2.04
CISPEP 1 THR A 23 PRO A 24 0 -1.19
CISPEP 2 LEU A 112 PRO A 113 0 5.38
CISPEP 3 PRO A 302 PRO A 303 0 3.13
CISPEP 4 GLY A 305 PRO A 306 0 1.26
CISPEP 5 THR B 23 PRO B 24 0 -0.58
CISPEP 6 LEU B 112 PRO B 113 0 2.84
CISPEP 7 PRO B 302 PRO B 303 0 2.59
CISPEP 8 GLY B 305 PRO B 306 0 -7.43
SITE 1 AC1 15 THR B 13 GLN B 14 TYR B 15 VAL B 31
SITE 2 AC1 15 ASP B 33 TYR B 78 THR B 80 PRO B 113
SITE 3 AC1 15 LEU B 116 ALA B 117 ASP B 221 THR B 222
SITE 4 AC1 15 GLY B 223 SER B 225 ASN B 255
SITE 1 AC2 16 THR A 13 GLN A 14 TYR A 15 VAL A 31
SITE 2 AC2 16 ASP A 33 TYR A 55 TYR A 78 SER A 79
SITE 3 AC2 16 THR A 80 LEU A 116 ALA A 117 VAL A 122
SITE 4 AC2 16 ASP A 221 THR A 222 GLY A 223 SER A 225
CRYST1 141.898 141.898 141.898 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 0.007047 0.000000 0.000000 0.00000
SCALE2 0.000000 0.007047 0.000000 0.00000
SCALE3 0.000000 0.000000 0.007047 0.00000
(ATOM LINES ARE NOT SHOWN.)
END