HEADER HYDROLASE 10-SEP-97 1AU4
TITLE CRYSTAL STRUCTURE OF THE CYSTEINE PROTEASE HUMAN CATHEPSIN K IN
TITLE 2 COMPLEX WITH A COVALENT PYRROLIDINONE INHIBITOR
COMPND MOL_ID: 1;
COMPND 2 MOLECULE: CATHEPSIN K;
COMPND 3 CHAIN: A;
COMPND 4 EC: 3.4.22.38;
COMPND 5 ENGINEERED: YES;
COMPND 6 OTHER_DETAILS: INHIBITOR COVALENTLY BOUND TO ACTIVE SITE CYS 25
SOURCE MOL_ID: 1;
SOURCE 2 ORGANISM_SCIENTIFIC: HOMO SAPIENS;
SOURCE 3 ORGANISM_COMMON: HUMAN;
SOURCE 4 ORGANISM_TAXID: 9606;
SOURCE 5 CELL_LINE: SF9;
SOURCE 6 CELL: OSTEOCLAST;
SOURCE 7 EXPRESSION_SYSTEM: SPODOPTERA FRUGIPERDA;
SOURCE 8 EXPRESSION_SYSTEM_COMMON: FALL ARMYWORM;
SOURCE 9 EXPRESSION_SYSTEM_TAXID: 7108;
SOURCE 10 EXPRESSION_SYSTEM_CELL_LINE: SF9;
SOURCE 11 EXPRESSION_SYSTEM_VECTOR: BACULOVIRUS
KEYWDS HYDROLASE, SULFHYDRYL PROTEINASE
EXPDTA X-RAY DIFFRACTION
AUTHOR B.ZHAO,W.W.SMITH,C.A.JANSON,S.S.ABDEL-MEGUID
REVDAT 4 02-AUG-23 1AU4 1 REMARK LINK
REVDAT 3 07-MAR-18 1AU4 1 REMARK
REVDAT 2 24-FEB-09 1AU4 1 VERSN
REVDAT 1 14-OCT-98 1AU4 0
JRNL AUTH R.W.MARQUIS,D.S.YAMASHITA,Y.RU,S.M.LOCASTRO,H.J.OH,
JRNL AUTH 2 K.F.ERHARD,R.L.DESJARLAIS,M.S.HEAD,W.W.SMITH,B.ZHAO,
JRNL AUTH 3 C.A.JANSON,S.S.ABDEL-MEGUID,T.A.TOMASZEK,M.A.LEVY,D.F.VEBER
JRNL TITL CONFORMATIONALLY CONSTRAINED 1,3-DIAMINO KETONES: A SERIES
JRNL TITL 2 OF POTENT INHIBITORS OF THE CYSTEINE PROTEASE CATHEPSIN K.
JRNL REF J.MED.CHEM. V. 41 3563 1998
JRNL REFN ISSN 0022-2623
JRNL PMID 9733481
JRNL DOI 10.1021/JM980295F
REMARK 2
REMARK 2 RESOLUTION. 2.30 ANGSTROMS.
REMARK 3
REMARK 3 REFINEMENT.
REMARK 3 PROGRAM : X-PLOR 3.1
REMARK 3 AUTHORS : BRUNGER
REMARK 3
REMARK 3 DATA USED IN REFINEMENT.
REMARK 3 RESOLUTION RANGE HIGH (ANGSTROMS) : 2.30
REMARK 3 RESOLUTION RANGE LOW (ANGSTROMS) : 8.00
REMARK 3 DATA CUTOFF (SIGMA(F)) : 2.000
REMARK 3 DATA CUTOFF HIGH (ABS(F)) : 1000000.000
REMARK 3 DATA CUTOFF LOW (ABS(F)) : 0.0010
REMARK 3 COMPLETENESS (WORKING+TEST) (%) : 80.0
REMARK 3 NUMBER OF REFLECTIONS : 7753
REMARK 3
REMARK 3 FIT TO DATA USED IN REFINEMENT.
REMARK 3 CROSS-VALIDATION METHOD : THROUGHOUT
REMARK 3 FREE R VALUE TEST SET SELECTION : RANDOM
REMARK 3 R VALUE (WORKING SET) : 0.266
REMARK 3 FREE R VALUE : 0.370
REMARK 3 FREE R VALUE TEST SET SIZE (%) : 10.400
REMARK 3 FREE R VALUE TEST SET COUNT : 803
REMARK 3 ESTIMATED ERROR OF FREE R VALUE : 0.013
REMARK 3
REMARK 3 FIT IN THE HIGHEST RESOLUTION BIN.
REMARK 3 TOTAL NUMBER OF BINS USED : 8
REMARK 3 BIN RESOLUTION RANGE HIGH (A) : 2.30
REMARK 3 BIN RESOLUTION RANGE LOW (A) : 2.40
REMARK 3 BIN COMPLETENESS (WORKING+TEST) (%) : 51.00
REMARK 3 REFLECTIONS IN BIN (WORKING SET) : 563
REMARK 3 BIN R VALUE (WORKING SET) : 0.3850
REMARK 3 BIN FREE R VALUE : 0.4790
REMARK 3 BIN FREE R VALUE TEST SET SIZE (%) : 8.20
REMARK 3 BIN FREE R VALUE TEST SET COUNT : 50
REMARK 3 ESTIMATED ERROR OF BIN FREE R VALUE : 0.068
REMARK 3
REMARK 3 NUMBER OF NON-HYDROGEN ATOMS USED IN REFINEMENT.
REMARK 3 PROTEIN ATOMS : 1649
REMARK 3 NUCLEIC ACID ATOMS : 0
REMARK 3 HETEROGEN ATOMS : 42
REMARK 3 SOLVENT ATOMS : 56
REMARK 3
REMARK 3 B VALUES.
REMARK 3 FROM WILSON PLOT (A**2) : 35.00
REMARK 3 MEAN B VALUE (OVERALL, A**2) : 17.50
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 COORDINATE ERROR.
REMARK 3 ESD FROM LUZZATI PLOT (A) : 0.39
REMARK 3 ESD FROM SIGMAA (A) : 0.48
REMARK 3 LOW RESOLUTION CUTOFF (A) : 8.00
REMARK 3
REMARK 3 CROSS-VALIDATED ESTIMATED COORDINATE ERROR.
REMARK 3 ESD FROM C-V LUZZATI PLOT (A) : 0.59
REMARK 3 ESD FROM C-V SIGMAA (A) : 0.61
REMARK 3
REMARK 3 RMS DEVIATIONS FROM IDEAL VALUES.
REMARK 3 BOND LENGTHS (A) : 0.015
REMARK 3 BOND ANGLES (DEGREES) : 1.900
REMARK 3 DIHEDRAL ANGLES (DEGREES) : 25.50
REMARK 3 IMPROPER ANGLES (DEGREES) : 1.730
REMARK 3
REMARK 3 ISOTROPIC THERMAL MODEL : OVERALL
REMARK 3
REMARK 3 ISOTROPIC THERMAL FACTOR RESTRAINTS. RMS SIGMA
REMARK 3 MAIN-CHAIN BOND (A**2) : NULL ; NULL
REMARK 3 MAIN-CHAIN ANGLE (A**2) : NULL ; NULL
REMARK 3 SIDE-CHAIN BOND (A**2) : NULL ; NULL
REMARK 3 SIDE-CHAIN ANGLE (A**2) : NULL ; NULL
REMARK 3
REMARK 3 NCS MODEL : NULL
REMARK 3
REMARK 3 NCS RESTRAINTS. RMS SIGMA/WEIGHT
REMARK 3 GROUP 1 POSITIONAL (A) : NULL ; NULL
REMARK 3 GROUP 1 B-FACTOR (A**2) : NULL ; NULL
REMARK 3
REMARK 3 PARAMETER FILE 1 : PARHCSDX.PRO
REMARK 3 PARAMETER FILE 2 : PARAM19.SOL
REMARK 3 PARAMETER FILE 3 : NULL
REMARK 3 TOPOLOGY FILE 1 : TOPHCSDX.PRO
REMARK 3 TOPOLOGY FILE 2 : NULL
REMARK 3 TOPOLOGY FILE 3 : NULL
REMARK 3
REMARK 3 OTHER REFINEMENT REMARKS: NULL
REMARK 4
REMARK 4 1AU4 COMPLIES WITH FORMAT V. 3.30, 13-JUL-11
REMARK 100
REMARK 100 THIS ENTRY HAS BEEN PROCESSED BY BNL.
REMARK 100 THE DEPOSITION ID IS D_1000171260.
REMARK 200
REMARK 200 EXPERIMENTAL DETAILS
REMARK 200 EXPERIMENT TYPE : X-RAY DIFFRACTION
REMARK 200 DATE OF DATA COLLECTION : AUG-96
REMARK 200 TEMPERATURE (KELVIN) : 293
REMARK 200 PH : 7.0
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 : SIEMENS
REMARK 200 MONOCHROMATIC OR LAUE (M/L) : M
REMARK 200 WAVELENGTH OR RANGE (A) : 1.5418
REMARK 200 MONOCHROMATOR : GRAPHITE(002)
REMARK 200 OPTICS : COLLIMATOR
REMARK 200
REMARK 200 DETECTOR TYPE : AREA DETECTOR
REMARK 200 DETECTOR MANUFACTURER : SIEMENS
REMARK 200 INTENSITY-INTEGRATION SOFTWARE : XENGEN
REMARK 200 DATA SCALING SOFTWARE : XENGEN
REMARK 200
REMARK 200 NUMBER OF UNIQUE REFLECTIONS : 9326
REMARK 200 RESOLUTION RANGE HIGH (A) : 2.300
REMARK 200 RESOLUTION RANGE LOW (A) : 25.000
REMARK 200 REJECTION CRITERIA (SIGMA(I)) : 2.000
REMARK 200
REMARK 200 OVERALL.
REMARK 200 COMPLETENESS FOR RANGE (%) : 93.0
REMARK 200 DATA REDUNDANCY : 2.900
REMARK 200 R MERGE (I) : 0.09600
REMARK 200 R SYM (I) : 0.09600
REMARK 200 <I/SIGMA(I)> FOR THE DATA SET : 7.6000
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) : 2.44
REMARK 200 COMPLETENESS FOR SHELL (%) : 80.0
REMARK 200 DATA REDUNDANCY IN SHELL : 2.00
REMARK 200 R MERGE FOR SHELL (I) : 0.30000
REMARK 200 R SYM FOR SHELL (I) : 0.30000
REMARK 200 <I/SIGMA(I)> FOR SHELL : 2.000
REMARK 200
REMARK 200 DIFFRACTION PROTOCOL: NULL
REMARK 200 METHOD USED TO DETERMINE THE STRUCTURE: MR
REMARK 200 SOFTWARE USED: X-PLOR 3.1
REMARK 200 STARTING MODEL: 1ATK
REMARK 200
REMARK 200 REMARK: NULL
REMARK 280
REMARK 280 CRYSTAL
REMARK 280 SOLVENT CONTENT, VS (%): 45.00
REMARK 280 MATTHEWS COEFFICIENT, VM (ANGSTROMS**3/DA): 2.26
REMARK 280
REMARK 280 CRYSTALLIZATION CONDITIONS: 30% MPD, 0.1M MES, 0.1M TRIS, PH 7.0
REMARK 290
REMARK 290 CRYSTALLOGRAPHIC SYMMETRY
REMARK 290 SYMMETRY OPERATORS FOR SPACE GROUP: P 21 21 21
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
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 19.97500
REMARK 290 SMTRY2 2 0.000000 -1.000000 0.000000 0.00000
REMARK 290 SMTRY3 2 0.000000 0.000000 1.000000 52.16500
REMARK 290 SMTRY1 3 -1.000000 0.000000 0.000000 0.00000
REMARK 290 SMTRY2 3 0.000000 1.000000 0.000000 25.49000
REMARK 290 SMTRY3 3 0.000000 0.000000 -1.000000 52.16500
REMARK 290 SMTRY1 4 1.000000 0.000000 0.000000 19.97500
REMARK 290 SMTRY2 4 0.000000 -1.000000 0.000000 25.49000
REMARK 290 SMTRY3 4 0.000000 0.000000 -1.000000 0.00000
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 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 500
REMARK 500 GEOMETRY AND STEREOCHEMISTRY
REMARK 500 SUBTOPIC: COVALENT BOND LENGTHS
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,2(A3,1X,A1,I4,A1,1X,A4,3X),1X,F6.3)
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 RES CSSEQI ATM2 DEVIATION
REMARK 500 TYR A 151 CE1 TYR A 151 CZ 0.082
REMARK 500 TYR A 151 CZ TYR A 151 CE2 0.081
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 LYS A 41 -78.83 -64.46
REMARK 500 THR A 42 46.62 -105.97
REMARK 500 GLN A 76 -61.81 -99.95
REMARK 500 TYR A 87 61.02 -159.61
REMARK 500 LYS A 103 121.20 -3.57
REMARK 500 ARG A 108 77.07 -113.98
REMARK 500 PRO A 114 115.21 -36.46
REMARK 500 SER A 146 -36.49 -137.46
REMARK 500 ASN A 199 -13.51 71.36
REMARK 500 CYS A 204 -10.74 60.69
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 INP A 300
DBREF 1AU4 A 1 215 UNP P43235 CATK_HUMAN 115 329
SEQRES 1 A 215 ALA PRO ASP SER VAL ASP TYR ARG LYS LYS GLY TYR VAL
SEQRES 2 A 215 THR PRO VAL LYS ASN GLN GLY GLN CYS GLY SER CYS TRP
SEQRES 3 A 215 ALA PHE SER SER VAL GLY ALA LEU GLU GLY GLN LEU LYS
SEQRES 4 A 215 LYS LYS THR GLY LYS LEU LEU ASN LEU SER PRO GLN ASN
SEQRES 5 A 215 LEU VAL ASP CYS VAL SER GLU ASN ASP GLY CYS GLY GLY
SEQRES 6 A 215 GLY TYR MET THR ASN ALA PHE GLN TYR VAL GLN LYS ASN
SEQRES 7 A 215 ARG GLY ILE ASP SER GLU ASP ALA TYR PRO TYR VAL GLY
SEQRES 8 A 215 GLN GLU GLU SER CYS MET TYR ASN PRO THR GLY LYS ALA
SEQRES 9 A 215 ALA LYS CYS ARG GLY TYR ARG GLU ILE PRO GLU GLY ASN
SEQRES 10 A 215 GLU LYS ALA LEU LYS ARG ALA VAL ALA ARG VAL GLY PRO
SEQRES 11 A 215 VAL SER VAL ALA ILE ASP ALA SER LEU THR SER PHE GLN
SEQRES 12 A 215 PHE TYR SER LYS GLY VAL TYR TYR ASP GLU SER CYS ASN
SEQRES 13 A 215 SER ASP ASN LEU ASN HIS ALA VAL LEU ALA VAL GLY TYR
SEQRES 14 A 215 GLY ILE GLN LYS GLY ASN LYS HIS TRP ILE ILE LYS ASN
SEQRES 15 A 215 SER TRP GLY GLU ASN TRP GLY ASN LYS GLY TYR ILE LEU
SEQRES 16 A 215 MET ALA ARG ASN LYS ASN ASN ALA CYS GLY ILE ALA ASN
SEQRES 17 A 215 LEU ALA SER PHE PRO LYS MET
HET INP A 300 42
HETNAM INP 4-[[N-[(PHENYLMETHOXY)CARBONYL]-/NL/N-LEUCYL]AMINO]-
HETNAM 2 INP 1[(2S)-2-[[[4-(PYRIDINYLMETHOXY)CARBONYL]AMINO]-4-
HETNAM 3 INP METHYLPENT/NYL]-3-PYRROLIDINONE/N
HETSYN INP PYRROLIDINONE
FORMUL 2 INP C31 H43 N5 O6
FORMUL 3 HOH *56(H2 O)
HELIX 1 1 CYS A 25 LYS A 41 1 17
HELIX 2 2 PRO A 50 CYS A 56 1 7
HELIX 3 3 GLY A 62 GLY A 64 5 3
HELIX 4 4 MET A 68 LYS A 77 1 10
HELIX 5 5 GLU A 84 TYR A 87 5 4
HELIX 6 6 GLU A 118 ARG A 127 1 10
HELIX 7 7 THR A 140 PHE A 144 1 5
HELIX 8 8 ALA A 203 GLY A 205 5 3
SHEET 1 A 2 TYR A 110 GLU A 112 0
SHEET 2 A 2 SER A 211 PRO A 213 -1 N PHE A 212 O ARG A 111
SHEET 1 B 2 VAL A 131 ILE A 135 0
SHEET 2 B 2 HIS A 162 ALA A 166 -1 N ALA A 166 O VAL A 131
SHEET 1 C 3 TYR A 169 GLN A 172 0
SHEET 2 C 3 ASN A 175 LYS A 181 -1 N HIS A 177 O GLY A 170
SHEET 3 C 3 TYR A 193 ALA A 197 -1 N MET A 196 O TRP A 178
SSBOND 1 CYS A 22 CYS A 63 1555 1555 2.06
SSBOND 2 CYS A 56 CYS A 96 1555 1555 2.05
SSBOND 3 CYS A 155 CYS A 204 1555 1555 2.02
LINK SG CYS A 25 C17 INP A 300 1555 1555 1.81
SITE 1 AC1 19 SER A 4 GLN A 19 GLN A 21 GLY A 23
SITE 2 AC1 19 SER A 24 CYS A 25 TRP A 26 GLU A 59
SITE 3 AC1 19 ASP A 61 GLY A 65 GLY A 66 TYR A 67
SITE 4 AC1 19 LYS A 147 ASN A 161 HIS A 162 ALA A 163
SITE 5 AC1 19 TRP A 184 LEU A 209 HOH A 315
CRYST1 39.950 50.980 104.330 90.00 90.00 90.00 P 21 21 21 4
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 0.025031 0.000000 0.000000 0.00000
SCALE2 0.000000 0.019616 0.000000 0.00000
SCALE3 0.000000 0.000000 0.009585 0.00000
(ATOM LINES ARE NOT SHOWN.)
END
