HEADER HYDROLASE 02-MAR-11 2YB9
TITLE CRYSTAL STRUCTURE OF HUMAN NEUTRAL ENDOPEPTIDASE COMPLEXED
TITLE 2 WITH A HETEROARYLALANINE DIACID.
COMPND MOL_ID: 1;
COMPND 2 MOLECULE: NEPRILYSIN;
COMPND 3 CHAIN: A;
COMPND 4 FRAGMENT: RESIDUES 55-750;
COMPND 5 SYNONYM: NEUTRAL ENDOPEPTIDASE, ATRIOPEPTIDASE, COMMON ACUTE
COMPND 6 LYMPHOCYTIC LEUKEMIA ANTIGEN, CALLA, ENKEPHALINASE, NEUTRAL
COMPND 7 ENDOPEPTIDASE 24.11, NEP, NEUTRAL ENDOPEPTIDASE, SKIN FIBROBLAST
COMPND 8 ELASTASE, SFE, CD10;
COMPND 9 EC: 3.4.24.11;
COMPND 10 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: SACCHAROMYCES CEREVISIAE;
SOURCE 6 EXPRESSION_SYSTEM_COMMON: BAKER'S YEAST;
SOURCE 7 EXPRESSION_SYSTEM_TAXID: 4932
KEYWDS HYDROLASE, NEPRILYSINE, METALLOPROTEINASE
EXPDTA X-RAY DIFFRACTION
AUTHOR M.S.GLOSSOP,R.J.BAZIN,K.N.DACK,S.DONE,D.N.A.FOX,G.A.MACDONALD,
AUTHOR 2 M.MILLS,D.R.OWEN,C.PHILLIPS,K.A.REEVES,T.J.RINGER,R.S.STRANG,
AUTHOR 3 C.A.L.WATSON
REVDAT 2 02-NOV-11 2YB9 1 JRNL REMARK VERSN
REVDAT 1 25-MAY-11 2YB9 0
JRNL AUTH M.S.GLOSSOP,R.J.BAZIN,K.N.DACK,D.N.A.FOX,G.A.MACDONALD,
JRNL AUTH 2 M.MILLS,D.R.OWEN,C.PHILLIPS,K.A.REEVES,T.J.RINGER,
JRNL AUTH 3 R.S.STRANG,C.A.L.WATSON
JRNL TITL SYNTHESIS AND EVALUATION OF HETEROARYLALANINE DIACIDS AS
JRNL TITL 2 POTENT AND SELECTIVE NEUTRAL ENDOPEPTIDASE INHIBITORS.
JRNL REF BIOORG.MED.CHEM.LETT. V. 21 3404 2011
JRNL REFN ISSN 0960-894X
JRNL PMID 21515054
JRNL DOI 10.1016/J.BMCL.2011.03.109
REMARK 2
REMARK 2 RESOLUTION. 2.40 ANGSTROMS.
REMARK 3
REMARK 3 REFINEMENT.
REMARK 3 PROGRAM : BUSTER 2.9.6
REMARK 3 AUTHORS : BRICOGNE,BLANC,BRANDL,FLENSBURG,KELLER,
REMARK 3 : PACIOREK,ROVERSI,SMART,VONRHEIN,WOMACK,
REMARK 3 : MATTHEWS,TEN EYCK,TRONRUD
REMARK 3
REMARK 3 DATA USED IN REFINEMENT.
REMARK 3 RESOLUTION RANGE HIGH (ANGSTROMS) : 2.40
REMARK 3 RESOLUTION RANGE LOW (ANGSTROMS) : 31.13
REMARK 3 DATA CUTOFF (SIGMA(F)) : 0.0
REMARK 3 COMPLETENESS FOR RANGE (%) : 99.27
REMARK 3 NUMBER OF REFLECTIONS : 29846
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) : 0.1758
REMARK 3 R VALUE (WORKING SET) : 0.1723
REMARK 3 FREE R VALUE : 0.2430
REMARK 3 FREE R VALUE TEST SET SIZE (%) : 5.08
REMARK 3 FREE R VALUE TEST SET COUNT : 1516
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 : 15
REMARK 3 BIN RESOLUTION RANGE HIGH (ANGSTROMS) : 2.40
REMARK 3 BIN RESOLUTION RANGE LOW (ANGSTROMS) : 2.48
REMARK 3 BIN COMPLETENESS (WORKING+TEST) (%) : 99.27
REMARK 3 REFLECTIONS IN BIN (WORKING + TEST SET) : 2844
REMARK 3 BIN R VALUE (WORKING + TEST SET) : 0.1926
REMARK 3 REFLECTIONS IN BIN (WORKING SET) : 2715
REMARK 3 BIN R VALUE (WORKING SET) : 0.1880
REMARK 3 BIN FREE R VALUE : 0.3003
REMARK 3 BIN FREE R VALUE TEST SET SIZE (%) : 4.54
REMARK 3 BIN FREE R VALUE TEST SET COUNT : 129
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 : 5595
REMARK 3 NUCLEIC ACID ATOMS : 0
REMARK 3 HETEROGEN ATOMS : 33
REMARK 3 SOLVENT ATOMS : 482
REMARK 3
REMARK 3 B VALUES.
REMARK 3 FROM WILSON PLOT (A**2) : 39.39
REMARK 3 MEAN B VALUE (OVERALL, A**2) : 31.24
REMARK 3 OVERALL ANISOTROPIC B VALUE.
REMARK 3 B11 (A**2) : -1.6395
REMARK 3 B22 (A**2) : -1.6395
REMARK 3 B33 (A**2) : 3.2791
REMARK 3 B12 (A**2) : 0.0000
REMARK 3 B13 (A**2) : 0.0000
REMARK 3 B23 (A**2) : 0.0000
REMARK 3
REMARK 3 ESTIMATED COORDINATE ERROR.
REMARK 3 ESD FROM LUZZATI PLOT (A) : 0.244
REMARK 3 DPI (BLOW EQ-10) BASED ON R VALUE (A) : 0.549
REMARK 3 DPI (BLOW EQ-9) BASED ON FREE R VALUE (A) : 0.269
REMARK 3 DPI (CRUICKSHANK) BASED ON R VALUE (A) : 0.441
REMARK 3 DPI (CRUICKSHANK) BASED ON FREE R VALUE (A) : 0.264
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 : 0.9421
REMARK 3 CORRELATION COEFFICIENT FO-FC FREE : 0.8979
REMARK 3
REMARK 3 NUMBER OF GEOMETRIC FUNCTION TERMS DEFINED : 15
REMARK 3 TERM COUNT WEIGHT FUNCTION.
REMARK 3 BOND LENGTHS : 5749 ; 2.00 ; HARMONIC
REMARK 3 BOND ANGLES : 7780 ; 2.00 ; HARMONIC
REMARK 3 TORSION ANGLES : 2027 ; 2.00 ; SINUSOIDAL
REMARK 3 TRIGONAL CARBON PLANES : 186 ; 2.00 ; HARMONIC
REMARK 3 GENERAL PLANES : 817 ; 5.00 ; HARMONIC
REMARK 3 ISOTROPIC THERMAL FACTORS : 5749 ; 20.00 ; HARMONIC
REMARK 3 BAD NON-BONDED CONTACTS : 0 ; 5.00 ; SEMIHARMONIC
REMARK 3 IMPROPER TORSIONS : NULL ; NULL ; NULL
REMARK 3 PSEUDOROTATION ANGLES : NULL ; NULL ; NULL
REMARK 3 CHIRAL IMPROPER TORSION : 733 ; 5.00 ; 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 : 7037 ; 4.00 ; SEMIHARMONIC
REMARK 3
REMARK 3 RMS DEVIATIONS FROM IDEAL VALUES.
REMARK 3 BOND LENGTHS (A) : 0.010
REMARK 3 BOND ANGLES (DEGREES) : 1.15
REMARK 3 PEPTIDE OMEGA TORSION ANGLES (DEGREES) : 2.89
REMARK 3 OTHER TORSION ANGLES (DEGREES) : 20.10
REMARK 3
REMARK 3 TLS DETAILS
REMARK 3 NUMBER OF TLS GROUPS : NULL
REMARK 3
REMARK 3 OTHER REFINEMENT REMARKS: GLYCOSYLATION NOT MODELLED
REMARK 4
REMARK 4 2YB9 COMPLIES WITH FORMAT V. 3.30, 13-JUL-11
REMARK 100
REMARK 100 THIS ENTRY HAS BEEN PROCESSED BY PDBE ON 02-MAR-11.
REMARK 100 THE PDBE ID CODE IS EBI-47509.
REMARK 200
REMARK 200 EXPERIMENTAL DETAILS
REMARK 200 EXPERIMENT TYPE : X-RAY DIFFRACTION
REMARK 200 DATE OF DATA COLLECTION : NULL
REMARK 200 TEMPERATURE (KELVIN) : 100
REMARK 200 PH : NULL
REMARK 200 NUMBER OF CRYSTALS USED : NULL
REMARK 200
REMARK 200 SYNCHROTRON (Y/N) : N
REMARK 200 RADIATION SOURCE : ROTATING ANODE
REMARK 200 BEAMLINE : NULL
REMARK 200 X-RAY GENERATOR MODEL : NULL
REMARK 200 MONOCHROMATIC OR LAUE (M/L) : M
REMARK 200 WAVELENGTH OR RANGE (A) : 1.5418
REMARK 200 MONOCHROMATOR : NULL
REMARK 200 OPTICS : NULL
REMARK 200
REMARK 200 DETECTOR TYPE : NULL
REMARK 200 DETECTOR MANUFACTURER : NULL
REMARK 200 INTENSITY-INTEGRATION SOFTWARE : NULL
REMARK 200 DATA SCALING SOFTWARE : NULL
REMARK 200
REMARK 200 NUMBER OF UNIQUE REFLECTIONS : 29854
REMARK 200 RESOLUTION RANGE HIGH (A) : 2.40
REMARK 200 RESOLUTION RANGE LOW (A) : 50.00
REMARK 200 REJECTION CRITERIA (SIGMA(I)) : 1.0
REMARK 200
REMARK 200 OVERALL.
REMARK 200 COMPLETENESS FOR RANGE (%) : 99.0
REMARK 200 DATA REDUNDANCY : 3.59
REMARK 200 R MERGE (I) : 0.07
REMARK 200 R SYM (I) : NULL
REMARK 200 <I/SIGMA(I)> FOR THE DATA SET : 14.50
REMARK 200
REMARK 200 IN THE HIGHEST RESOLUTION SHELL.
REMARK 200 HIGHEST RESOLUTION SHELL, RANGE HIGH (A) : NULL
REMARK 200 HIGHEST RESOLUTION SHELL, RANGE LOW (A) : NULL
REMARK 200 COMPLETENESS FOR SHELL (%) : NULL
REMARK 200 DATA REDUNDANCY IN SHELL : NULL
REMARK 200 R MERGE FOR SHELL (I) : NULL
REMARK 200 R SYM FOR SHELL (I) : NULL
REMARK 200 <I/SIGMA(I)> FOR SHELL : NULL
REMARK 200
REMARK 200 DIFFRACTION PROTOCOL: SINGLE WAVELENGTH
REMARK 200 METHOD USED TO DETERMINE THE STRUCTURE: OTHER
REMARK 200 SOFTWARE USED: NULL
REMARK 200 STARTING MODEL: NULL
REMARK 200
REMARK 200 REMARK: NONE
REMARK 280
REMARK 280 CRYSTAL
REMARK 280 SOLVENT CONTENT, VS (%): 48.34
REMARK 280 MATTHEWS COEFFICIENT, VM (ANGSTROMS**3/DA): 2.38
REMARK 280
REMARK 280 CRYSTALLIZATION CONDITIONS: NULL
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 75.19600
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 37.59800
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 37.59800
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 75.19600
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: DIMERIC
REMARK 350 SOFTWARE DETERMINED QUATERNARY STRUCTURE: DIMERIC
REMARK 350 SOFTWARE USED: PISA
REMARK 350 TOTAL BURIED SURFACE AREA: 1920 ANGSTROM**2
REMARK 350 SURFACE AREA OF THE COMPLEX: 55460 ANGSTROM**2
REMARK 350 CHANGE IN SOLVENT FREE ENERGY: -13.5 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 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 112.79400
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 TRP A 181 132.33 -34.11
REMARK 500 LEU A 199 -54.09 66.86
REMARK 500 ASN A 210 86.29 -152.23
REMARK 500 SER A 211 -5.03 -56.29
REMARK 500 TYR A 231 -9.38 -59.33
REMARK 500 LYS A 318 -82.16 -82.37
REMARK 500 LEU A 382 -166.97 -102.16
REMARK 500 LEU A 559 58.25 -92.17
REMARK 500 LEU A 602 83.85 -67.29
REMARK 500 ASP A 678 47.28 -98.02
REMARK 500 VAL A 748 -73.63 -115.82
REMARK 500
REMARK 500 REMARK: NULL
REMARK 500
REMARK 500 GEOMETRY AND STEREOCHEMISTRY
REMARK 500 SUBTOPIC: CHIRAL CENTERS
REMARK 500
REMARK 500 UNEXPECTED CONFIGURATION OF THE FOLLOWING CHIRAL
REMARK 500 CENTER(S) USING IMPROPER CA--C--CB--N CHIRALITY
REMARK 500 FOR AMINO ACIDS AND C1'--O4'--N1(N9)--C2' FOR
REMARK 500 NUCLEIC ACIDS OR EQUIVALENT ANGLE
REMARK 500 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,A1,6X,F5.1,6X,A1,10X,A1,3X,A16)
REMARK 500
REMARK 500 M RES CSSEQI IMPROPER EXPECTED FOUND DETAILS
REMARK 500 LEU A 160 24.7 L L OUTSIDE RANGE
REMARK 500 LYS A 209 24.5 L L OUTSIDE RANGE
REMARK 500 VAL A 275 22.9 L L OUTSIDE RANGE
REMARK 500 LYS A 318 21.6 L L OUTSIDE RANGE
REMARK 500 ASN A 334 24.8 L L OUTSIDE RANGE
REMARK 500 ARG A 394 23.8 L L OUTSIDE RANGE
REMARK 500 VAL A 414 21.9 L L OUTSIDE RANGE
REMARK 500
REMARK 500 REMARK: NULL
REMARK 620
REMARK 620 METAL COORDINATION
REMARK 620 (M=MODEL NUMBER; RES=RESIDUE NAME; C=CHAIN IDENTIFIER;
REMARK 620 SSEQ=SEQUENCE NUMBER; I=INSERTION CODE):
REMARK 620
REMARK 620 COORDINATION ANGLES FOR: M RES CSSEQI METAL
REMARK 620 ZN A1750 ZN
REMARK 620 N RES CSSEQI ATOM
REMARK 620 1 HA0 A1751 OG2
REMARK 620 2 HA0 A1751 OG1 54.5
REMARK 620 3 GLU A 646 OE1 94.4 148.0
REMARK 620 4 HIS A 587 NE2 132.5 102.3 105.4
REMARK 620 5 HIS A 583 NE2 120.9 95.8 94.7 100.3
REMARK 620 N 1 2 3 4
REMARK 800
REMARK 800 SITE
REMARK 800 SITE_IDENTIFIER: AC1
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: BINDING SITE FOR RESIDUE ZN A1750
REMARK 800
REMARK 800 SITE_IDENTIFIER: AC2
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: BINDING SITE FOR RESIDUE HA0 A1751
REMARK 900
REMARK 900 RELATED ENTRIES
REMARK 900 RELATED ID: 1QVD RELATED DB: PDB
REMARK 900 THE COMMON ACUTE LYMPHOBLASTIC LEUKEMIA ANTIGEN IN
REMARK 900 COMPLEXWITH A NATURAL P5-P2' SUBSTRATE, BEFORE, DURING
REMARK 900 AND AFTERMOLECULAR SIMULATION IN WATER.
REMARK 900 RELATED ID: 1Y8J RELATED DB: PDB
REMARK 900 CRYSTAL STRUCTURE OF HUMAN NEP COMPLEXED WITH AN
REMARK 900 IMIDAZO[4,5-C]PYRIDINE INHIBITOR
REMARK 900 RELATED ID: 1R1J RELATED DB: PDB
REMARK 900 STRUCTURAL ANALYSIS OF NEPRILYSIN WITH VARIOUS SPECIFIC
REMARK 900 ANDPOTENT INHIBITORS
REMARK 900 RELATED ID: 1DL9 RELATED DB: PDB
REMARK 900 THREE-DIMENSIONAL CONSTRUCTION OF THE ACTIVE SITE (REGION
REMARK 900 507-749) OF HUMAN NEUTRAL ENDOPEPTIDASE (EC.3.4.24.11)
REMARK 900 RELATED ID: 1R1H RELATED DB: PDB
REMARK 900 STRUCTURAL ANALYSIS OF NEPRILYSIN WITH VARIOUS SPECIFIC
REMARK 900 ANDPOTENT INHIBITORS
REMARK 900 RELATED ID: 1DMT RELATED DB: PDB
REMARK 900 STRUCTURE OF HUMAN NEUTRAL ENDOPEPTIDASE COMPLEXED WITH
REMARK 900 PHOSPHORAMIDON
REMARK 900 RELATED ID: 1R1I RELATED DB: PDB
REMARK 900 STRUCTURAL ANALYSIS OF NEPRILYSIN WITH VARIOUS SPECIFIC
REMARK 900 ANDPOTENT INHIBITORS
DBREF 2YB9 A 54 749 UNP P08473 NEP_HUMAN 55 750
SEQRES 1 A 696 GLY ILE CYS LYS SER SER ASP CYS ILE LYS SER ALA ALA
SEQRES 2 A 696 ARG LEU ILE GLN ASN MET ASP ALA THR THR GLU PRO CYS
SEQRES 3 A 696 THR ASP PHE PHE LYS TYR ALA CYS GLY GLY TRP LEU LYS
SEQRES 4 A 696 ARG ASN VAL ILE PRO GLU THR SER SER ARG TYR GLY ASN
SEQRES 5 A 696 PHE ASP ILE LEU ARG ASP GLU LEU GLU VAL VAL LEU LYS
SEQRES 6 A 696 ASP VAL LEU GLN GLU PRO LYS THR GLU ASP ILE VAL ALA
SEQRES 7 A 696 VAL GLN LYS ALA LYS ALA LEU TYR ARG SER CYS ILE ASN
SEQRES 8 A 696 GLU SER ALA ILE ASP SER ARG GLY GLY GLU PRO LEU LEU
SEQRES 9 A 696 LYS LEU LEU PRO ASP ILE TYR GLY TRP PRO VAL ALA THR
SEQRES 10 A 696 GLU ASN TRP GLU GLN LYS TYR GLY ALA SER TRP THR ALA
SEQRES 11 A 696 GLU LYS ALA ILE ALA GLN LEU ASN SER LYS TYR GLY LYS
SEQRES 12 A 696 LYS VAL LEU ILE ASN LEU PHE VAL GLY THR ASP ASP LYS
SEQRES 13 A 696 ASN SER VAL ASN HIS VAL ILE HIS ILE ASP GLN PRO ARG
SEQRES 14 A 696 LEU GLY LEU PRO SER ARG ASP TYR TYR GLU CYS THR GLY
SEQRES 15 A 696 ILE TYR LYS GLU ALA CYS THR ALA TYR VAL ASP PHE MET
SEQRES 16 A 696 ILE SER VAL ALA ARG LEU ILE ARG GLN GLU GLU ARG LEU
SEQRES 17 A 696 PRO ILE ASP GLU ASN GLN LEU ALA LEU GLU MET ASN LYS
SEQRES 18 A 696 VAL MET GLU LEU GLU LYS GLU ILE ALA ASN ALA THR ALA
SEQRES 19 A 696 LYS PRO GLU ASP ARG ASN ASP PRO MET LEU LEU TYR ASN
SEQRES 20 A 696 LYS MET THR LEU ALA GLN ILE GLN ASN ASN PHE SER LEU
SEQRES 21 A 696 GLU ILE ASN GLY LYS PRO PHE SER TRP LEU ASN PHE THR
SEQRES 22 A 696 ASN GLU ILE MET SER THR VAL ASN ILE SER ILE THR ASN
SEQRES 23 A 696 GLU GLU ASP VAL VAL VAL TYR ALA PRO GLU TYR LEU THR
SEQRES 24 A 696 LYS LEU LYS PRO ILE LEU THR LYS TYR SER ALA ARG ASP
SEQRES 25 A 696 LEU GLN ASN LEU MET SER TRP ARG PHE ILE MET ASP LEU
SEQRES 26 A 696 VAL SER SER LEU SER ARG THR TYR LYS GLU SER ARG ASN
SEQRES 27 A 696 ALA PHE ARG LYS ALA LEU TYR GLY THR THR SER GLU THR
SEQRES 28 A 696 ALA THR TRP ARG ARG CYS ALA ASN TYR VAL ASN GLY ASN
SEQRES 29 A 696 MET GLU ASN ALA VAL GLY ARG LEU TYR VAL GLU ALA ALA
SEQRES 30 A 696 PHE ALA GLY GLU SER LYS HIS VAL VAL GLU ASP LEU ILE
SEQRES 31 A 696 ALA GLN ILE ARG GLU VAL PHE ILE GLN THR LEU ASP ASP
SEQRES 32 A 696 LEU THR TRP MET ASP ALA GLU THR LYS LYS ARG ALA GLU
SEQRES 33 A 696 GLU LYS ALA LEU ALA ILE LYS GLU ARG ILE GLY TYR PRO
SEQRES 34 A 696 ASP ASP ILE VAL SER ASN ASP ASN LYS LEU ASN ASN GLU
SEQRES 35 A 696 TYR LEU GLU LEU ASN TYR LYS GLU ASP GLU TYR PHE GLU
SEQRES 36 A 696 ASN ILE ILE GLN ASN LEU LYS PHE SER GLN SER LYS GLN
SEQRES 37 A 696 LEU LYS LYS LEU ARG GLU LYS VAL ASP LYS ASP GLU TRP
SEQRES 38 A 696 ILE SER GLY ALA ALA VAL VAL ASN ALA PHE TYR SER SER
SEQRES 39 A 696 GLY ARG ASN GLN ILE VAL PHE PRO ALA GLY ILE LEU GLN
SEQRES 40 A 696 PRO PRO PHE PHE SER ALA GLN GLN SER ASN SER LEU ASN
SEQRES 41 A 696 TYR GLY GLY ILE GLY MET VAL ILE GLY HIS GLU ILE THR
SEQRES 42 A 696 HIS GLY PHE ASP ASP ASN GLY ARG ASN PHE ASN LYS ASP
SEQRES 43 A 696 GLY ASP LEU VAL ASP TRP TRP THR GLN GLN SER ALA SER
SEQRES 44 A 696 ASN PHE LYS GLU GLN SER GLN CYS MET VAL TYR GLN TYR
SEQRES 45 A 696 GLY ASN PHE SER TRP ASP LEU ALA GLY GLY GLN HIS LEU
SEQRES 46 A 696 ASN GLY ILE ASN THR LEU GLY GLU ASN ILE ALA ASP ASN
SEQRES 47 A 696 GLY GLY LEU GLY GLN ALA TYR ARG ALA TYR GLN ASN TYR
SEQRES 48 A 696 ILE LYS LYS ASN GLY GLU GLU LYS LEU LEU PRO GLY LEU
SEQRES 49 A 696 ASP LEU ASN HIS LYS GLN LEU PHE PHE LEU ASN PHE ALA
SEQRES 50 A 696 GLN VAL TRP CYS GLY THR TYR ARG PRO GLU TYR ALA VAL
SEQRES 51 A 696 ASN SER ILE LYS THR ASP VAL HIS SER PRO GLY ASN PHE
SEQRES 52 A 696 ARG ILE ILE GLY THR LEU GLN ASN SER ALA GLU PHE SER
SEQRES 53 A 696 GLU ALA PHE HIS CYS ARG LYS ASN SER TYR MET ASN PRO
SEQRES 54 A 696 GLU LYS LYS CYS ARG VAL TRP
HET ZN A1750 1
HET HA0 A1751 32
HETNAM ZN ZINC ION
HETNAM HA0 HETEROARYLALANINE 5-PHENYL OXAZOLE
FORMUL 2 ZN ZN 2+
FORMUL 3 HA0 C24 H30 N2 O6
FORMUL 4 HOH *482(H2 O)
HELIX 1 1 SER A 58 MET A 72 1 15
HELIX 2 2 ASP A 81 ASN A 94 1 14
HELIX 3 3 ASN A 105 GLU A 123 1 19
HELIX 4 4 ILE A 129 ASN A 144 1 16
HELIX 5 5 ASN A 144 ARG A 151 1 8
HELIX 6 6 GLY A 153 LEU A 160 1 8
HELIX 7 7 PRO A 161 TYR A 164 5 4
HELIX 8 8 TRP A 166 THR A 170 5 5
HELIX 9 9 ASN A 172 TYR A 177 1 6
HELIX 10 10 THR A 182 GLY A 195 1 14
HELIX 11 11 SER A 227 CYS A 233 5 7
HELIX 12 12 THR A 234 ILE A 236 5 3
HELIX 13 13 TYR A 237 GLU A 259 1 23
HELIX 14 14 ASP A 264 THR A 286 1 23
HELIX 15 15 LYS A 288 ARG A 292 5 5
HELIX 16 16 ASP A 294 TYR A 299 1 6
HELIX 17 17 LEU A 304 PHE A 311 1 8
HELIX 18 18 SER A 321 SER A 331 1 11
HELIX 19 19 THR A 332 ASN A 334 5 3
HELIX 20 20 ALA A 347 THR A 359 1 13
HELIX 21 21 SER A 362 VAL A 379 1 18
HELIX 22 22 SER A 380 LEU A 382 5 3
HELIX 23 23 SER A 383 SER A 389 1 7
HELIX 24 24 ARG A 390 GLY A 399 1 10
HELIX 25 25 ALA A 405 MET A 418 1 14
HELIX 26 26 MET A 418 PHE A 431 1 14
HELIX 27 27 GLY A 433 LEU A 457 1 25
HELIX 28 28 ASP A 461 ALA A 474 1 14
HELIX 29 29 ASP A 483 ASN A 488 1 6
HELIX 30 30 ASN A 488 GLU A 495 1 8
HELIX 31 31 GLU A 505 LYS A 523 1 19
HELIX 32 32 GLY A 557 LEU A 559 5 3
HELIX 33 33 SER A 569 GLY A 576 1 8
HELIX 34 34 GLY A 576 HIS A 587 1 12
HELIX 35 35 GLY A 588 ASP A 590 5 3
HELIX 36 36 ASN A 592 ASN A 595 5 4
HELIX 37 37 THR A 607 ASN A 627 1 21
HELIX 38 38 THR A 643 GLY A 669 1 27
HELIX 39 39 ASN A 680 VAL A 692 1 13
HELIX 40 40 ARG A 698 ASP A 709 1 12
HELIX 41 41 PRO A 713 ASN A 724 1 12
HELIX 42 42 SER A 725 PHE A 732 1 8
SHEET 1 AA 2 ARG A 102 GLY A 104 0
SHEET 2 AA 2 GLY A 695 TYR A 697 -1 O THR A 696 N TYR A 103
SHEET 1 AB 4 ASN A 201 ASP A 207 0
SHEET 2 AB 4 ASN A 210 ASP A 219 -1 N ASN A 210 O ASP A 207
SHEET 3 AB 4 ASP A 342 VAL A 345 1 O ASP A 342 N ILE A 216
SHEET 4 AB 4 LYS A 301 THR A 303 -1 O MET A 302 N VAL A 343
SHEET 1 AC 3 LYS A 476 GLY A 480 0
SHEET 2 AC 3 GLN A 551 PRO A 555 1 O ILE A 552 N ARG A 478
SHEET 3 AC 3 PHE A 544 SER A 546 -1 O PHE A 544 N VAL A 553
SHEET 1 AD 2 SER A 629 TRP A 630 0
SHEET 2 AD 2 GLN A 636 HIS A 637 -1 O GLN A 636 N TRP A 630
SSBOND 1 CYS A 79 CYS A 734 1555 1555 2.03
SSBOND 2 CYS A 142 CYS A 410 1555 1555 2.05
LINK ZN ZN A1750 OG1 HA0 A1751 1555 1555 2.63
LINK ZN ZN A1750 OG2 HA0 A1751 1555 1555 2.06
LINK ZN ZN A1750 OE1 GLU A 646 1555 1555 1.94
LINK ZN ZN A1750 NE2 HIS A 587 1555 1555 2.02
LINK ZN ZN A1750 NE2 HIS A 583 1555 1555 2.02
CISPEP 1 LYS A 318 PRO A 319 0 5.90
CISPEP 2 PRO A 561 PRO A 562 0 5.00
SITE 1 AC1 5 HIS A 583 HIS A 587 GLU A 646 HIS A 711
SITE 2 AC1 5 HA0 A1751
SITE 1 AC2 19 ARG A 102 PHE A 106 ASP A 107 ARG A 110
SITE 2 AC2 19 ASN A 542 ALA A 543 HIS A 583 GLU A 584
SITE 3 AC2 19 HIS A 587 GLU A 646 TRP A 693 GLY A 695
SITE 4 AC2 19 TYR A 697 HIS A 711 GLY A 714 ARG A 717
SITE 5 AC2 19 ZN A1750 HOH A2053 HOH A2482
CRYST1 107.841 107.841 112.794 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 0.009273 0.005354 0.000000 0.00000
SCALE2 0.000000 0.010707 0.000000 0.00000
SCALE3 0.000000 0.000000 0.008866 0.00000
(ATOM LINES ARE NOT SHOWN.)
END
