HEADER HYDROLASE/HYDROLASE INHIBITOR 16-NOV-12 4I03
TITLE HUMAN MMP12 IN COMPLEX WITH A PEG-LINKED BIFUNCTIONAL L-GLUTAMATE
TITLE 2 MOTIF INHIBITOR
COMPND MOL_ID: 1;
COMPND 2 MOLECULE: MACROPHAGE METALLOELASTASE;
COMPND 3 CHAIN: A;
COMPND 4 FRAGMENT: CATALYTIC DOMAIN (UNP RESIDUES 106-263);
COMPND 5 SYNONYM: MME, MACROPHAGE ELASTASE, ME, HME, MATRIX METALLOPROTEINASE-
COMPND 6 12, MMP-12;
COMPND 7 EC: 3.4.24.65;
COMPND 8 ENGINEERED: YES;
COMPND 9 MUTATION: YES
SOURCE MOL_ID: 1;
SOURCE 2 ORGANISM_SCIENTIFIC: HOMO SAPIENS;
SOURCE 3 ORGANISM_COMMON: HUMAN;
SOURCE 4 ORGANISM_TAXID: 9606;
SOURCE 5 STRAIN: ESCHERICHIA COLI;
SOURCE 6 GENE: HME, MMP12;
SOURCE 7 EXPRESSION_SYSTEM: ESCHERICHIA COLI;
SOURCE 8 EXPRESSION_SYSTEM_TAXID: 511693;
SOURCE 9 EXPRESSION_SYSTEM_STRAIN: BL21;
SOURCE 10 EXPRESSION_SYSTEM_VECTOR_TYPE: PLASMID;
SOURCE 11 EXPRESSION_SYSTEM_PLASMID: PET24A
KEYWDS SELECTIVE CARBOXYLATE BASED MMP-12 BIFUNCTIONAL INHIBITOR, METZINCIN,
KEYWDS 2 ZINC PROTEASE, HYDROLASE-HYDROLASE INHIBITOR COMPLEX
EXPDTA X-RAY DIFFRACTION
AUTHOR E.A.STURA,L.VERA,L.DEVEL,E.CASSAR-LAJEUNESSE,V.DIVE
REVDAT 3 28-FEB-24 4I03 1 REMARK SEQADV LINK
REVDAT 2 03-JUL-13 4I03 1 JRNL
REVDAT 1 24-APR-13 4I03 0
JRNL AUTH C.ANTONI,L.VERA,L.DEVEL,M.P.CATALANI,B.CZARNY,
JRNL AUTH 2 E.CASSAR-LAJEUNESSE,E.NUTI,A.ROSSELLO,V.DIVE,E.A.STURA
JRNL TITL CRYSTALLIZATION OF BI-FUNCTIONAL LIGAND PROTEIN COMPLEXES.
JRNL REF J.STRUCT.BIOL. V. 182 246 2013
JRNL REFN ISSN 1047-8477
JRNL PMID 23567804
JRNL DOI 10.1016/J.JSB.2013.03.015
REMARK 1
REMARK 1 REFERENCE 1
REMARK 1 AUTH A.ROSSELLO,E.NUTI,M.P.CATALANI,P.CARELLI,E.ORLANDINI,
REMARK 1 AUTH 2 S.RAPPOSELLI,T.TUCCINARDI,S.J.ATKINSON,G.MURPHY,A.BALSAMO
REMARK 1 TITL A NEW DEVELOPMENT OF MATRIX METALLOPROTEINASE INHIBITORS:
REMARK 1 TITL 2 TWIN HYDROXAMIC ACIDS AS POTENT INHIBITORS OF MMPS.
REMARK 1 REF BIOORG.MED.CHEM.LETT. V. 15 2311 2005
REMARK 1 REFN ISSN 0960-894X
REMARK 1 PMID 15837315
REMARK 1 DOI 10.1016/J.BMCL.2005.03.002
REMARK 1 REFERENCE 2
REMARK 1 REF TO BE PUBLISHED
REMARK 1 REFN ISSN 0960-894X
REMARK 2
REMARK 2 RESOLUTION. 1.70 ANGSTROMS.
REMARK 3
REMARK 3 REFINEMENT.
REMARK 3 PROGRAM : REFMAC 5.5.0109
REMARK 3 AUTHORS : MURSHUDOV,SKUBAK,LEBEDEV,PANNU,STEINER,
REMARK 3 : NICHOLLS,WINN,LONG,VAGIN
REMARK 3
REMARK 3 REFINEMENT TARGET : MAXIMUM LIKELIHOOD
REMARK 3
REMARK 3 DATA USED IN REFINEMENT.
REMARK 3 RESOLUTION RANGE HIGH (ANGSTROMS) : 1.70
REMARK 3 RESOLUTION RANGE LOW (ANGSTROMS) : 36.67
REMARK 3 DATA CUTOFF (SIGMA(F)) : 0.000
REMARK 3 COMPLETENESS FOR RANGE (%) : 100.0
REMARK 3 NUMBER OF REFLECTIONS : 15828
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) : 0.146
REMARK 3 R VALUE (WORKING SET) : 0.144
REMARK 3 FREE R VALUE : 0.194
REMARK 3 FREE R VALUE TEST SET SIZE (%) : 5.000
REMARK 3 FREE R VALUE TEST SET COUNT : 834
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) : 1.70
REMARK 3 BIN RESOLUTION RANGE LOW (A) : 1.74
REMARK 3 REFLECTION IN BIN (WORKING SET) : 1124
REMARK 3 BIN COMPLETENESS (WORKING+TEST) (%) : 100.0
REMARK 3 BIN R VALUE (WORKING SET) : 0.2520
REMARK 3 BIN FREE R VALUE SET COUNT : 60
REMARK 3 BIN FREE R VALUE : 0.2960
REMARK 3
REMARK 3 NUMBER OF NON-HYDROGEN ATOMS USED IN REFINEMENT.
REMARK 3 PROTEIN ATOMS : 1242
REMARK 3 NUCLEIC ACID ATOMS : 0
REMARK 3 HETEROGEN ATOMS : 139
REMARK 3 SOLVENT ATOMS : 171
REMARK 3
REMARK 3 B VALUES.
REMARK 3 FROM WILSON PLOT (A**2) : 28.35
REMARK 3 MEAN B VALUE (OVERALL, A**2) : 19.56
REMARK 3 OVERALL ANISOTROPIC B VALUE.
REMARK 3 B11 (A**2) : 0.05000
REMARK 3 B22 (A**2) : -0.05000
REMARK 3 B33 (A**2) : 0.05000
REMARK 3 B12 (A**2) : 0.00000
REMARK 3 B13 (A**2) : 0.06000
REMARK 3 B23 (A**2) : 0.00000
REMARK 3
REMARK 3 ESTIMATED OVERALL COORDINATE ERROR.
REMARK 3 ESU BASED ON R VALUE (A): 0.104
REMARK 3 ESU BASED ON FREE R VALUE (A): 0.108
REMARK 3 ESU BASED ON MAXIMUM LIKELIHOOD (A): 0.074
REMARK 3 ESU FOR B VALUES BASED ON MAXIMUM LIKELIHOOD (A**2): 2.294
REMARK 3
REMARK 3 CORRELATION COEFFICIENTS.
REMARK 3 CORRELATION COEFFICIENT FO-FC : 0.974
REMARK 3 CORRELATION COEFFICIENT FO-FC FREE : 0.960
REMARK 3
REMARK 3 RMS DEVIATIONS FROM IDEAL VALUES COUNT RMS WEIGHT
REMARK 3 BOND LENGTHS REFINED ATOMS (A): 1501 ; 0.022 ; 0.021
REMARK 3 BOND LENGTHS OTHERS (A): 1045 ; 0.002 ; 0.020
REMARK 3 BOND ANGLES REFINED ATOMS (DEGREES): 2015 ; 2.038 ; 1.999
REMARK 3 BOND ANGLES OTHERS (DEGREES): 2515 ; 1.033 ; 3.000
REMARK 3 TORSION ANGLES, PERIOD 1 (DEGREES): 176 ; 7.055 ; 5.000
REMARK 3 TORSION ANGLES, PERIOD 2 (DEGREES): 66 ;35.842 ;22.879
REMARK 3 TORSION ANGLES, PERIOD 3 (DEGREES): 215 ;16.634 ;15.000
REMARK 3 TORSION ANGLES, PERIOD 4 (DEGREES): 9 ;18.651 ;15.000
REMARK 3 CHIRAL-CENTER RESTRAINTS (A**3): 197 ; 0.114 ; 0.200
REMARK 3 GENERAL PLANES REFINED ATOMS (A): 1673 ; 0.011 ; 0.020
REMARK 3 GENERAL PLANES OTHERS (A): 343 ; 0.003 ; 0.020
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): 836 ; 1.372 ; 1.500
REMARK 3 MAIN-CHAIN BOND OTHER ATOMS (A**2): 347 ; 0.414 ; 1.500
REMARK 3 MAIN-CHAIN ANGLE REFINED ATOMS (A**2): 1349 ; 2.290 ; 2.000
REMARK 3 MAIN-CHAIN ANGLE OTHER ATOMS (A**2): NULL ; NULL ; NULL
REMARK 3 SIDE-CHAIN BOND REFINED ATOMS (A**2): 665 ; 3.131 ; 3.000
REMARK 3 SIDE-CHAIN BOND OTHER ATOMS (A**2): NULL ; NULL ; NULL
REMARK 3 SIDE-CHAIN ANGLE REFINED ATOMS (A**2): 664 ; 4.865 ; 4.500
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 : NULL
REMARK 3
REMARK 3 BULK SOLVENT MODELLING.
REMARK 3 METHOD USED : 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 RIDING
REMARK 3 POSITIONS
REMARK 4
REMARK 4 4I03 COMPLIES WITH FORMAT V. 3.30, 13-JUL-11
REMARK 100
REMARK 100 THIS ENTRY HAS BEEN PROCESSED BY RCSB ON 21-NOV-12.
REMARK 100 THE DEPOSITION ID IS D_1000076135.
REMARK 200
REMARK 200 EXPERIMENTAL DETAILS
REMARK 200 EXPERIMENT TYPE : X-RAY DIFFRACTION
REMARK 200 DATE OF DATA COLLECTION : 12-OCT-12
REMARK 200 TEMPERATURE (KELVIN) : 100
REMARK 200 PH : 8.5
REMARK 200 NUMBER OF CRYSTALS USED : 1
REMARK 200
REMARK 200 SYNCHROTRON (Y/N) : Y
REMARK 200 RADIATION SOURCE : SOLEIL
REMARK 200 BEAMLINE : PROXIMA 1
REMARK 200 X-RAY GENERATOR MODEL : NULL
REMARK 200 MONOCHROMATIC OR LAUE (M/L) : M
REMARK 200 WAVELENGTH OR RANGE (A) : 0.980110
REMARK 200 MONOCHROMATOR : SAGITALLY FOCUSED SI(111)
REMARK 200 OPTICS : MIRRORS
REMARK 200
REMARK 200 DETECTOR TYPE : PIXEL
REMARK 200 DETECTOR MANUFACTURER : PSI PILATUS 6M
REMARK 200 INTENSITY-INTEGRATION SOFTWARE : XDS
REMARK 200 DATA SCALING SOFTWARE : XDS
REMARK 200
REMARK 200 NUMBER OF UNIQUE REFLECTIONS : 16663
REMARK 200 RESOLUTION RANGE HIGH (A) : 1.700
REMARK 200 RESOLUTION RANGE LOW (A) : 50.000
REMARK 200 REJECTION CRITERIA (SIGMA(I)) : -4.000
REMARK 200
REMARK 200 OVERALL.
REMARK 200 COMPLETENESS FOR RANGE (%) : 99.2
REMARK 200 DATA REDUNDANCY : 4.140
REMARK 200 R MERGE (I) : 0.10200
REMARK 200 R SYM (I) : 0.08900
REMARK 200 <I/SIGMA(I)> FOR THE DATA SET : 9.5200
REMARK 200
REMARK 200 IN THE HIGHEST RESOLUTION SHELL.
REMARK 200 HIGHEST RESOLUTION SHELL, RANGE HIGH (A) : 1.70
REMARK 200 HIGHEST RESOLUTION SHELL, RANGE LOW (A) : 1.80
REMARK 200 COMPLETENESS FOR SHELL (%) : 97.2
REMARK 200 DATA REDUNDANCY IN SHELL : 4.02
REMARK 200 R MERGE FOR SHELL (I) : 0.88700
REMARK 200 R SYM FOR SHELL (I) : 0.76800
REMARK 200 <I/SIGMA(I)> FOR SHELL : 1.710
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 (%): 43.45
REMARK 280 MATTHEWS COEFFICIENT, VM (ANGSTROMS**3/DA): 2.18
REMARK 280
REMARK 280 CRYSTALLIZATION CONDITIONS: PROTEIN SOLUTION: 222 MICROM MMP12
REMARK 280 MUTANT E219A 106 MICROM BIFUNCTIONAL INHIBITOR LD884. RESERVOIR:
REMARK 280 27% PEG 10K, 150MM IMIDAZOLE PIPERIDINE, PH 8.5. CRYOPROTECTANT:
REMARK 280 5 % DI-ETHYLENE GLYCOL + 5 % ETHYLENE GLYCOL + 10 % 1,2-
REMARK 280 PROPANEDIOL + 5 % DMSO + 5 % GLYCEROL, 25% MPEG 5K, 100MM (NA
REMARK 280 ACETATE, ADA, BICINE 10% PH 4.0/90% PH 9.0), VAPOR DIFFUSION,
REMARK 280 SITTING DROP, TEMPERATURE 293K
REMARK 290
REMARK 290 CRYSTALLOGRAPHIC SYMMETRY
REMARK 290 SYMMETRY OPERATORS FOR SPACE GROUP: C 1 2 1
REMARK 290
REMARK 290 SYMOP SYMMETRY
REMARK 290 NNNMMM OPERATOR
REMARK 290 1555 X,Y,Z
REMARK 290 2555 -X,Y,-Z
REMARK 290 3555 X+1/2,Y+1/2,Z
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 0.00000
REMARK 290 SMTRY2 2 0.000000 1.000000 0.000000 0.00000
REMARK 290 SMTRY3 2 0.000000 0.000000 -1.000000 0.00000
REMARK 290 SMTRY1 3 1.000000 0.000000 0.000000 25.89500
REMARK 290 SMTRY2 3 0.000000 1.000000 0.000000 30.05000
REMARK 290 SMTRY3 3 0.000000 0.000000 1.000000 0.00000
REMARK 290 SMTRY1 4 -1.000000 0.000000 0.000000 25.89500
REMARK 290 SMTRY2 4 0.000000 1.000000 0.000000 30.05000
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 300 REMARK: THE BIFUNCTIONAL INHIBITOR JOINS TWO MMP-12 MOLECULES
REMARK 300 CREATING A CRYSTALLOGRAPHIC DIMER
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 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 HOH A 484 LIES ON A SPECIAL POSITION.
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 ARG A 110 42.92 -106.67
REMARK 500 HIS A 172 76.42 -115.93
REMARK 500 HIS A 206 -155.45 -134.43
REMARK 500 THR A 247 1.07 91.30
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 CA A 304 CA
REMARK 620 N RES CSSEQI ATOM
REMARK 620 1 ASP A 124 OD2
REMARK 620 2 ASP A 124 OD1 52.8
REMARK 620 3 GLU A 199 O 138.4 162.3
REMARK 620 4 GLU A 199 OE2 86.7 87.4 80.7
REMARK 620 5 GLU A 201 O 74.8 122.2 75.0 114.6
REMARK 620 6 HOH A 420 O 98.0 86.3 102.8 167.6 77.7
REMARK 620 7 HOH A 429 O 136.7 84.0 82.6 88.4 144.1 80.3
REMARK 620 N 1 2 3 4 5 6
REMARK 620
REMARK 620 COORDINATION ANGLES FOR: M RES CSSEQI METAL
REMARK 620 CA A 303 CA
REMARK 620 N RES CSSEQI ATOM
REMARK 620 1 ASP A 158 O
REMARK 620 2 GLY A 190 O 166.0
REMARK 620 3 GLY A 192 O 92.5 89.0
REMARK 620 4 ASP A 194 OD1 91.4 102.4 92.2
REMARK 620 5 HOH A 414 O 90.9 85.6 170.7 96.4
REMARK 620 6 HOH A 419 O 84.1 82.3 83.0 173.3 88.7
REMARK 620 N 1 2 3 4 5
REMARK 620
REMARK 620 COORDINATION ANGLES FOR: M RES CSSEQI METAL
REMARK 620 ZN A 302 ZN
REMARK 620 N RES CSSEQI ATOM
REMARK 620 1 HIS A 168 NE2
REMARK 620 2 ASP A 170 OD2 108.2
REMARK 620 3 HIS A 196 ND1 106.3 93.3
REMARK 620 N 1 2
REMARK 620
REMARK 620 COORDINATION ANGLES FOR: M RES CSSEQI METAL
REMARK 620 CA A 305 CA
REMARK 620 N RES CSSEQI ATOM
REMARK 620 1 ASP A 175 OD1
REMARK 620 2 GLY A 176 O 85.2
REMARK 620 3 GLY A 178 O 85.0 82.6
REMARK 620 4 ILE A 180 O 97.8 176.9 96.7
REMARK 620 5 ASP A 198 OD2 93.9 89.8 172.4 91.0
REMARK 620 6 GLU A 201 OE2 168.7 87.6 85.4 89.3 94.9
REMARK 620 N 1 2 3 4 5
REMARK 620
REMARK 620 COORDINATION ANGLES FOR: M RES CSSEQI METAL
REMARK 620 ZN A 301 ZN
REMARK 620 N RES CSSEQI ATOM
REMARK 620 1 HIS A 222 NE2
REMARK 620 2 HIS A 228 NE2 105.1
REMARK 620 3 L88 A 306 O4 131.4 91.8
REMARK 620 4 L88 A 306 O4E 87.4 136.5 52.4
REMARK 620 N 1 2 3
REMARK 800
REMARK 800 SITE
REMARK 800 SITE_IDENTIFIER: AC1
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: BINDING SITE FOR RESIDUE ZN A 301
REMARK 800
REMARK 800 SITE_IDENTIFIER: AC2
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: BINDING SITE FOR RESIDUE ZN A 302
REMARK 800
REMARK 800 SITE_IDENTIFIER: AC3
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: BINDING SITE FOR RESIDUE CA A 303
REMARK 800
REMARK 800 SITE_IDENTIFIER: AC4
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: BINDING SITE FOR RESIDUE CA A 304
REMARK 800
REMARK 800 SITE_IDENTIFIER: AC5
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: BINDING SITE FOR RESIDUE CA A 305
REMARK 800
REMARK 800 SITE_IDENTIFIER: AC6
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: BINDING SITE FOR RESIDUE L88 A 306
REMARK 800
REMARK 800 SITE_IDENTIFIER: AC7
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: BINDING SITE FOR RESIDUE GOL A 307
REMARK 800
REMARK 800 SITE_IDENTIFIER: AC8
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: BINDING SITE FOR RESIDUE GOL A 308
REMARK 800
REMARK 800 SITE_IDENTIFIER: AC9
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: BINDING SITE FOR RESIDUE GOL A 309
REMARK 800
REMARK 800 SITE_IDENTIFIER: BC1
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: BINDING SITE FOR RESIDUE PGO A 310
REMARK 800
REMARK 800 SITE_IDENTIFIER: BC2
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: BINDING SITE FOR RESIDUE PGO A 311
REMARK 800
REMARK 800 SITE_IDENTIFIER: BC3
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: BINDING SITE FOR RESIDUE DMS A 312
REMARK 800
REMARK 800 SITE_IDENTIFIER: BC4
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: BINDING SITE FOR RESIDUE DMS A 313
REMARK 800
REMARK 800 SITE_IDENTIFIER: BC5
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: BINDING SITE FOR RESIDUE EDO A 314
REMARK 800
REMARK 800 SITE_IDENTIFIER: BC6
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: BINDING SITE FOR RESIDUE EDO A 315
REMARK 800
REMARK 800 SITE_IDENTIFIER: BC7
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: BINDING SITE FOR RESIDUE EDO A 316
REMARK 800
REMARK 800 SITE_IDENTIFIER: BC8
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: BINDING SITE FOR RESIDUE EDO A 317
REMARK 800
REMARK 800 SITE_IDENTIFIER: BC9
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: BINDING SITE FOR RESIDUE PEG A 318
REMARK 900
REMARK 900 RELATED ENTRIES
REMARK 900 RELATED ID: 4EFS RELATED DB: PDB
REMARK 900 HUMAN MMP12 IN COMPLEX WITH L-GLUTAMATE MOTIF INHIBITOR
REMARK 900 RELATED ID: 3TS4 RELATED DB: PDB
REMARK 900 HUMAN MMP12 IN COMPLEX WITH L-GLUTAMATE MOTIF INHIBITOR
REMARK 900 RELATED ID: 3TSK RELATED DB: PDB
REMARK 900 HUMAN MMP12 IN COMPLEX WITH L-GLUTAMATE MOTIF INHIBITOR
REMARK 900 RELATED ID: 4H30 RELATED DB: PDB
REMARK 900 CRYSTAL STRUCTURE OF THE CATALYTIC DOMAIN OF MMP-12 IN COMPLEX WITH
REMARK 900 A TWIN INHIBITOR.
REMARK 900 RELATED ID: 4H49 RELATED DB: PDB
REMARK 900 CRYSTAL STRUCTURE OF CRYSTAL STRUCTURE OF THE CATALYTIC DOMAIN OF
REMARK 900 MMP-12 IN COMPLEX WITH A TWIN INHIBITOR.
DBREF 4I03 A 106 263 UNP P39900 MMP12_HUMAN 106 263
SEQADV 4I03 MET A 105 UNP P39900 INITIATING METHIONINE
SEQADV 4I03 ASP A 171 UNP P39900 PHE 171 ENGINEERED MUTATION
SEQADV 4I03 ALA A 219 UNP P39900 GLU 219 ENGINEERED MUTATION
SEQRES 1 A 159 MET GLY PRO VAL TRP ARG LYS HIS TYR ILE THR TYR ARG
SEQRES 2 A 159 ILE ASN ASN TYR THR PRO ASP MET ASN ARG GLU ASP VAL
SEQRES 3 A 159 ASP TYR ALA ILE ARG LYS ALA PHE GLN VAL TRP SER ASN
SEQRES 4 A 159 VAL THR PRO LEU LYS PHE SER LYS ILE ASN THR GLY MET
SEQRES 5 A 159 ALA ASP ILE LEU VAL VAL PHE ALA ARG GLY ALA HIS GLY
SEQRES 6 A 159 ASP ASP HIS ALA PHE ASP GLY LYS GLY GLY ILE LEU ALA
SEQRES 7 A 159 HIS ALA PHE GLY PRO GLY SER GLY ILE GLY GLY ASP ALA
SEQRES 8 A 159 HIS PHE ASP GLU ASP GLU PHE TRP THR THR HIS SER GLY
SEQRES 9 A 159 GLY THR ASN LEU PHE LEU THR ALA VAL HIS ALA ILE GLY
SEQRES 10 A 159 HIS SER LEU GLY LEU GLY HIS SER SER ASP PRO LYS ALA
SEQRES 11 A 159 VAL MET PHE PRO THR TYR LYS TYR VAL ASP ILE ASN THR
SEQRES 12 A 159 PHE ARG LEU SER ALA ASP ASP ILE ARG GLY ILE GLN SER
SEQRES 13 A 159 LEU TYR GLY
HET ZN A 301 1
HET ZN A 302 1
HET CA A 303 1
HET CA A 304 1
HET CA A 305 1
HET L88 A 306 75
HET GOL A 307 6
HET GOL A 308 12
HET GOL A 309 6
HET PGO A 310 5
HET PGO A 311 5
HET DMS A 312 4
HET DMS A 313 4
HET EDO A 314 4
HET EDO A 315 4
HET EDO A 316 4
HET EDO A 317 4
HET PEG A 318 7
HETNAM ZN ZINC ION
HETNAM CA CALCIUM ION
HETNAM L88 (4R,22R)-5,21-DIOXO-4,22-BIS({3-[4-(4-PHENYLTHIOPHEN-2-
HETNAM 2 L88 YL)PHENYL]PROPANOYL}AMINO)-10,13,16-TRIOXA-6,20-
HETNAM 3 L88 DIAZAPENTACOSANE-1,25-DIOIC ACID
HETNAM GOL GLYCEROL
HETNAM PGO S-1,2-PROPANEDIOL
HETNAM DMS DIMETHYL SULFOXIDE
HETNAM EDO 1,2-ETHANEDIOL
HETNAM PEG DI(HYDROXYETHYL)ETHER
HETSYN GOL GLYCERIN; PROPANE-1,2,3-TRIOL
HETSYN EDO ETHYLENE GLYCOL
FORMUL 2 ZN 2(ZN 2+)
FORMUL 4 CA 3(CA 2+)
FORMUL 7 L88 C58 H66 N4 O11 S2
FORMUL 8 GOL 3(C3 H8 O3)
FORMUL 11 PGO 2(C3 H8 O2)
FORMUL 13 DMS 2(C2 H6 O S)
FORMUL 15 EDO 4(C2 H6 O2)
FORMUL 19 PEG C4 H10 O3
FORMUL 20 HOH *171(H2 O)
HELIX 1 1 ASN A 126 ASN A 143 1 18
HELIX 2 2 LEU A 212 LEU A 224 1 13
HELIX 3 3 SER A 251 GLY A 263 1 13
SHEET 1 A 5 LYS A 148 LYS A 151 0
SHEET 2 A 5 TYR A 113 ILE A 118 1 N ILE A 114 O LYS A 148
SHEET 3 A 5 ILE A 159 ALA A 164 1 O VAL A 161 N ARG A 117
SHEET 4 A 5 ALA A 195 ASP A 198 1 O PHE A 197 N VAL A 162
SHEET 5 A 5 ALA A 182 ALA A 184 -1 N HIS A 183 O HIS A 196
SHEET 1 B 2 TRP A 203 THR A 204 0
SHEET 2 B 2 THR A 210 ASN A 211 1 O THR A 210 N THR A 204
LINK OD2 ASP A 124 CA CA A 304 1555 1555 2.31
LINK OD1 ASP A 124 CA CA A 304 1555 1555 2.56
LINK O ASP A 158 CA CA A 303 1555 1555 2.24
LINK NE2 HIS A 168 ZN ZN A 302 1555 1555 2.06
LINK OD2 ASP A 170 ZN ZN A 302 1555 1555 1.88
LINK OD1 ASP A 175 CA CA A 305 1555 1555 2.29
LINK O GLY A 176 CA CA A 305 1555 1555 2.36
LINK O GLY A 178 CA CA A 305 1555 1555 2.36
LINK O ILE A 180 CA CA A 305 1555 1555 2.31
LINK O GLY A 190 CA CA A 303 1555 1555 2.39
LINK O GLY A 192 CA CA A 303 1555 1555 2.16
LINK OD1 ASP A 194 CA CA A 303 1555 1555 2.50
LINK ND1 HIS A 196 ZN ZN A 302 1555 1555 2.01
LINK OD2 ASP A 198 CA CA A 305 1555 1555 2.27
LINK O GLU A 199 CA CA A 304 1555 1555 2.33
LINK OE2 GLU A 199 CA CA A 304 1555 1555 2.37
LINK O GLU A 201 CA CA A 304 1555 1555 2.46
LINK OE2 GLU A 201 CA CA A 305 1555 1555 2.30
LINK NE2 HIS A 222 ZN ZN A 301 1555 1555 2.06
LINK NE2 HIS A 228 ZN ZN A 301 1555 1555 2.11
LINK ZN ZN A 301 O4 L88 A 306 1555 1555 2.39
LINK ZN ZN A 301 O4E L88 A 306 1555 1555 2.44
LINK CA CA A 303 O HOH A 414 1555 1555 2.31
LINK CA CA A 303 O HOH A 419 1555 1555 2.45
LINK CA CA A 304 O HOH A 420 1555 1555 2.48
LINK CA CA A 304 O HOH A 429 1555 1555 2.50
SITE 1 AC1 4 HIS A 218 HIS A 222 HIS A 228 L88 A 306
SITE 1 AC2 4 HIS A 168 ASP A 170 HIS A 183 HIS A 196
SITE 1 AC3 6 ASP A 158 GLY A 190 GLY A 192 ASP A 194
SITE 2 AC3 6 HOH A 414 HOH A 419
SITE 1 AC4 5 ASP A 124 GLU A 199 GLU A 201 HOH A 420
SITE 2 AC4 5 HOH A 429
SITE 1 AC5 6 ASP A 175 GLY A 176 GLY A 178 ILE A 180
SITE 2 AC5 6 ASP A 198 GLU A 201
SITE 1 AC6 21 GLY A 179 ILE A 180 LEU A 181 ALA A 182
SITE 2 AC6 21 HIS A 218 HIS A 222 HIS A 228 PRO A 232
SITE 3 AC6 21 LYS A 233 ALA A 234 VAL A 235 PHE A 237
SITE 4 AC6 21 PRO A 238 THR A 239 TYR A 240 LYS A 241
SITE 5 AC6 21 ZN A 301 PGO A 311 HOH A 401 HOH A 513
SITE 6 AC6 21 HOH A 521
SITE 1 AC7 11 TYR A 113 THR A 115 MET A 125 ASN A 126
SITE 2 AC7 11 ASP A 129 SER A 150 THR A 204 THR A 205
SITE 3 AC7 11 HOH A 435 HOH A 454 HOH A 468
SITE 1 AC8 9 MET A 105 GLY A 106 VAL A 108 ARG A 110
SITE 2 AC8 9 GLY A 176 LYS A 177 SER A 260 LEU A 261
SITE 3 AC8 9 EDO A 315
SITE 1 AC9 8 MET A 105 ASP A 171 GLY A 225 LEU A 226
SITE 2 AC9 8 GLY A 227 SER A 260 LEU A 261 HOH A 428
SITE 1 BC1 1 ARG A 256
SITE 1 BC2 5 GLY A 179 THR A 239 TYR A 240 L88 A 306
SITE 2 BC2 5 HOH A 500
SITE 1 BC3 4 HIS A 172 HIS A 183 ALA A 184 EDO A 316
SITE 1 BC4 7 ASP A 175 LYS A 177 GLY A 178 GLY A 179
SITE 2 BC4 7 THR A 239 LYS A 241 EDO A 315
SITE 1 BC5 4 ARG A 110 ASP A 200 EDO A 315 HOH A 505
SITE 1 BC6 6 MET A 105 ASP A 175 PHE A 237 GOL A 308
SITE 2 BC6 6 DMS A 313 EDO A 314
SITE 1 BC7 5 ALA A 184 DMS A 312 HOH A 401 HOH A 421
SITE 2 BC7 5 HOH A 503
SITE 1 BC8 3 HIS A 168 HIS A 196 HOH A 405
SITE 1 BC9 8 THR A 145 PRO A 146 SER A 150 PHE A 202
SITE 2 BC9 8 HIS A 206 HOH A 454 HOH A 519 HOH A 520
CRYST1 51.790 60.100 54.920 90.00 116.67 90.00 C 1 2 1 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 0.019309 0.000000 0.009699 0.00000
SCALE2 0.000000 0.016639 0.000000 0.00000
SCALE3 0.000000 0.000000 0.020376 0.00000
(ATOM LINES ARE NOT SHOWN.)
END
