HEADER HYDROLASE/HYDROLASE INHIBITOR 24-AUG-12 4GR3
TITLE CRYSTAL STRUCTURE OF THE CATALYTIC DOMAIN OF HUMAN MMP12 IN COMPLEX
TITLE 2 WITH SELECTIVE PHOSPHINIC INHIBITOR RXP470A
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 GENE: HME, MMP12;
SOURCE 6 EXPRESSION_SYSTEM: ESCHERICHIA COLI;
SOURCE 7 EXPRESSION_SYSTEM_TAXID: 511693;
SOURCE 8 EXPRESSION_SYSTEM_STRAIN: BL21;
SOURCE 9 EXPRESSION_SYSTEM_VECTOR_TYPE: PLASMID;
SOURCE 10 EXPRESSION_SYSTEM_PLASMID: PET24A
KEYWDS POTENT SELECTIVE PHOSPHINIC INHIBITOR, METZINCIN, ZINC PROTEASE,
KEYWDS 2 HYDROLASE-HYDROLASE INHIBITOR COMPLEX
EXPDTA X-RAY DIFFRACTION
AUTHOR E.A.STURA,L.VERA,F.BEAU,L.DEVEL,E.CASSAR-LAJEUNESSE,V.DIVE
REVDAT 3 13-SEP-23 4GR3 1 COMPND REMARK SEQADV HETNAM
REVDAT 3 2 1 LINK
REVDAT 2 22-MAY-13 4GR3 1 JRNL
REVDAT 1 06-FEB-13 4GR3 0
JRNL AUTH B.CZARNY,E.A.STURA,L.DEVEL,L.VERA,E.CASSAR-LAJEUNESSE,
JRNL AUTH 2 F.BEAU,V.CALDERONE,M.FRAGAI,C.LUCHINAT,V.DIVE
JRNL TITL MOLECULAR DETERMINANTS OF A SELECTIVE MATRIX
JRNL TITL 2 METALLOPROTEASE-12 INHIBITOR: INSIGHTS FROM CRYSTALLOGRAPHY
JRNL TITL 3 AND THERMODYNAMIC STUDIES.
JRNL REF J.MED.CHEM. V. 56 1149 2013
JRNL REFN ISSN 0022-2623
JRNL PMID 23343195
JRNL DOI 10.1021/JM301574D
REMARK 2
REMARK 2 RESOLUTION. 1.49 ANGSTROMS.
REMARK 3
REMARK 3 REFINEMENT.
REMARK 3 PROGRAM : PHENIX (PHENIX.REFINE: 1.8_1069)
REMARK 3 AUTHORS : PAUL ADAMS,PAVEL AFONINE,VINCENT CHEN,IAN
REMARK 3 : DAVIS,KRESHNA GOPAL,RALF GROSSE-KUNSTLEVE,
REMARK 3 : LI-WEI HUNG,ROBERT IMMORMINO,TOM IOERGER,
REMARK 3 : AIRLIE MCCOY,ERIK MCKEE,NIGEL MORIARTY,
REMARK 3 : REETAL PAI,RANDY READ,JANE RICHARDSON,
REMARK 3 : DAVID RICHARDSON,TOD ROMO,JIM SACCHETTINI,
REMARK 3 : NICHOLAS SAUTER,JACOB SMITH,LAURENT
REMARK 3 : STORONI,TOM TERWILLIGER,PETER ZWART
REMARK 3
REMARK 3 REFINEMENT TARGET : ML
REMARK 3
REMARK 3 DATA USED IN REFINEMENT.
REMARK 3 RESOLUTION RANGE HIGH (ANGSTROMS) : 1.49
REMARK 3 RESOLUTION RANGE LOW (ANGSTROMS) : 46.57
REMARK 3 MIN(FOBS/SIGMA_FOBS) : 2.000
REMARK 3 COMPLETENESS FOR RANGE (%) : 99.8
REMARK 3 NUMBER OF REFLECTIONS : 27033
REMARK 3
REMARK 3 FIT TO DATA USED IN REFINEMENT.
REMARK 3 R VALUE (WORKING + TEST SET) : 0.182
REMARK 3 R VALUE (WORKING SET) : 0.180
REMARK 3 FREE R VALUE : 0.216
REMARK 3 FREE R VALUE TEST SET SIZE (%) : 5.000
REMARK 3 FREE R VALUE TEST SET COUNT : 1352
REMARK 3
REMARK 3 FIT TO DATA USED IN REFINEMENT (IN BINS).
REMARK 3 BIN RESOLUTION RANGE COMPL. NWORK NFREE RWORK RFREE
REMARK 3 1 46.5872 - 3.2188 1.00 2748 145 0.1590 0.1828
REMARK 3 2 3.2188 - 2.5549 1.00 2611 137 0.1633 0.1870
REMARK 3 3 2.5549 - 2.2320 1.00 2567 136 0.1702 0.2171
REMARK 3 4 2.2320 - 2.0279 1.00 2560 134 0.1740 0.2163
REMARK 3 5 2.0279 - 1.8825 1.00 2567 135 0.1814 0.2178
REMARK 3 6 1.8825 - 1.7715 1.00 2546 135 0.1931 0.2598
REMARK 3 7 1.7715 - 1.6828 1.00 2540 133 0.2140 0.2571
REMARK 3 8 1.6828 - 1.6096 1.00 2549 134 0.2265 0.2741
REMARK 3 9 1.6096 - 1.5476 1.00 2511 132 0.2477 0.2894
REMARK 3 10 1.5476 - 1.4942 0.98 2482 131 0.2757 0.3122
REMARK 3
REMARK 3 BULK SOLVENT MODELLING.
REMARK 3 METHOD USED : FLAT BULK SOLVENT MODEL
REMARK 3 SOLVENT RADIUS : 1.11
REMARK 3 SHRINKAGE RADIUS : 0.90
REMARK 3 K_SOL : NULL
REMARK 3 B_SOL : NULL
REMARK 3
REMARK 3 ERROR ESTIMATES.
REMARK 3 COORDINATE ERROR (MAXIMUM-LIKELIHOOD BASED) : 0.170
REMARK 3 PHASE ERROR (DEGREES, MAXIMUM-LIKELIHOOD BASED) : 21.020
REMARK 3
REMARK 3 B VALUES.
REMARK 3 FROM WILSON PLOT (A**2) : 21.51
REMARK 3 MEAN B VALUE (OVERALL, A**2) : NULL
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 TWINNING INFORMATION.
REMARK 3 FRACTION: NULL
REMARK 3 OPERATOR: NULL
REMARK 3
REMARK 3 DEVIATIONS FROM IDEAL VALUES.
REMARK 3 RMSD COUNT
REMARK 3 BOND : 0.006 1372
REMARK 3 ANGLE : 1.091 1866
REMARK 3 CHIRALITY : 0.073 189
REMARK 3 PLANARITY : 0.005 245
REMARK 3 DIHEDRAL : 16.814 480
REMARK 3
REMARK 3 TLS DETAILS
REMARK 3 NUMBER OF TLS GROUPS : NULL
REMARK 3
REMARK 3 NCS DETAILS
REMARK 3 NUMBER OF NCS GROUPS : NULL
REMARK 3
REMARK 3 OTHER REFINEMENT REMARKS: NULL
REMARK 4
REMARK 4 4GR3 COMPLIES WITH FORMAT V. 3.30, 13-JUL-11
REMARK 100
REMARK 100 THIS ENTRY HAS BEEN PROCESSED BY RCSB ON 04-OCT-12.
REMARK 100 THE DEPOSITION ID IS D_1000074531.
REMARK 200
REMARK 200 EXPERIMENTAL DETAILS
REMARK 200 EXPERIMENT TYPE : X-RAY DIFFRACTION
REMARK 200 DATE OF DATA COLLECTION : 20-SEP-09
REMARK 200 TEMPERATURE (KELVIN) : 100
REMARK 200 PH : 8.0
REMARK 200 NUMBER OF CRYSTALS USED : 1
REMARK 200
REMARK 200 SYNCHROTRON (Y/N) : Y
REMARK 200 RADIATION SOURCE : ESRF
REMARK 200 BEAMLINE : ID14-2
REMARK 200 X-RAY GENERATOR MODEL : NULL
REMARK 200 MONOCHROMATIC OR LAUE (M/L) : M
REMARK 200 WAVELENGTH OR RANGE (A) : 0.9334
REMARK 200 MONOCHROMATOR : SI 111 CHANNEL
REMARK 200 OPTICS : TOROIDAL MIRROR
REMARK 200
REMARK 200 DETECTOR TYPE : CCD
REMARK 200 DETECTOR MANUFACTURER : ADSC QUANTUM 4
REMARK 200 INTENSITY-INTEGRATION SOFTWARE : XDS
REMARK 200 DATA SCALING SOFTWARE : XDS
REMARK 200
REMARK 200 NUMBER OF UNIQUE REFLECTIONS : 27049
REMARK 200 RESOLUTION RANGE HIGH (A) : 1.490
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 (%) : 99.7
REMARK 200 DATA REDUNDANCY : 7.900
REMARK 200 R MERGE (I) : 0.10600
REMARK 200 R SYM (I) : 0.09900
REMARK 200 <I/SIGMA(I)> FOR THE DATA SET : 16.1200
REMARK 200
REMARK 200 IN THE HIGHEST RESOLUTION SHELL.
REMARK 200 HIGHEST RESOLUTION SHELL, RANGE HIGH (A) : 1.49
REMARK 200 HIGHEST RESOLUTION SHELL, RANGE LOW (A) : 1.58
REMARK 200 COMPLETENESS FOR SHELL (%) : 98.9
REMARK 200 DATA REDUNDANCY IN SHELL : 6.98
REMARK 200 R MERGE FOR SHELL (I) : 1.17000
REMARK 200 R SYM FOR SHELL (I) : 1.10000
REMARK 200 <I/SIGMA(I)> FOR SHELL : 1.970
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: 4GQL
REMARK 200
REMARK 200 REMARK: NULL
REMARK 280
REMARK 280 CRYSTAL
REMARK 280 SOLVENT CONTENT, VS (%): 46.64
REMARK 280 MATTHEWS COEFFICIENT, VM (ANGSTROMS**3/DA): 2.31
REMARK 280
REMARK 280 CRYSTALLIZATION CONDITIONS: PROTEIN: HMMP12(F171D) 643 MICROM.
REMARK 280 RESERVOIR: 18% PEG 10000, 0.2 M IMIDAZOLE MALATE PH 8.0.
REMARK 280 CRYOPROTECTANT: 27% PEG 8000, 15% MONOMETHYLPEG 550, 10%
REMARK 280 GLYCEROL, 0.09 M TRIS-HCL, PH 8.0, VAPOR DIFFUSION, SITTING DROP,
REMARK 280 TEMPERATURE 293K
REMARK 290
REMARK 290 CRYSTALLOGRAPHIC SYMMETRY
REMARK 290 SYMMETRY OPERATORS FOR SPACE GROUP: P 21 21 2
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 34.48000
REMARK 290 SMTRY2 3 0.000000 1.000000 0.000000 31.56500
REMARK 290 SMTRY3 3 0.000000 0.000000 -1.000000 0.00000
REMARK 290 SMTRY1 4 1.000000 0.000000 0.000000 34.48000
REMARK 290 SMTRY2 4 0.000000 -1.000000 0.000000 31.56500
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 SOFTWARE DETERMINED QUATERNARY STRUCTURE: MONOMERIC
REMARK 350 SOFTWARE USED: PISA
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 454 LIES ON A SPECIAL POSITION.
REMARK 375 HOH A 632 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 HIS A 206 -151.09 -145.00
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 51.4
REMARK 620 3 GLU A 199 O 137.6 161.9
REMARK 620 4 GLU A 199 OE2 87.7 86.5 79.1
REMARK 620 5 GLU A 201 O 76.0 121.8 75.1 117.8
REMARK 620 6 HOH A 425 O 96.4 82.3 108.7 161.6 80.6
REMARK 620 7 HOH A 437 O 138.9 87.9 80.0 84.2 142.1 81.0
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 165.4
REMARK 620 3 GLY A 192 O 96.3 90.2
REMARK 620 4 ASP A 194 OD2 90.9 102.5 86.9
REMARK 620 5 HOH A 417 O 87.5 83.4 166.8 105.6
REMARK 620 6 HOH A 424 O 83.9 85.0 77.0 162.4 90.9
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 OD1 110.5
REMARK 620 3 HIS A 183 NE2 121.5 110.3
REMARK 620 4 HIS A 196 ND1 107.3 95.5 108.5
REMARK 620 N 1 2 3
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 OD2
REMARK 620 2 GLY A 176 O 86.8
REMARK 620 3 GLY A 178 O 83.9 90.7
REMARK 620 4 ILE A 180 O 92.4 178.4 90.5
REMARK 620 5 ASP A 198 OD1 99.4 86.6 175.7 92.2
REMARK 620 6 GLU A 201 OE2 171.0 94.3 87.2 86.8 89.6
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 218 NE2
REMARK 620 2 HIS A 222 NE2 103.4
REMARK 620 3 HIS A 228 NE2 112.0 104.1
REMARK 620 4 R45 A 306 O3 120.1 119.1 97.0
REMARK 620 N 1 2 3
REMARK 630
REMARK 630 MOLECULE TYPE: PEPTIDE-LIKE ENZYME INHIBITOR
REMARK 630 MOLECULE NAME: N-{(2S)-3-[(S)-(4-BROMOPHENYL)(HYDROXY)PHOSPHORYL]-
REMARK 630 2-[(3-PHENYL-1,2-OXAZOL-5-YL)METHYL]PROPANOYL}-L-ALPHA-GLUTAMYL-L-
REMARK 630 AL PHA-GLUTAMINE
REMARK 630 (M=MODEL NUMBER; RES=RESIDUE NAME; C=CHAIN IDENTIFIER;
REMARK 630 SSSEQ=SEQUENCE NUMBER; I=INSERTION CODE.)
REMARK 630
REMARK 630 M RES C SSSEQI
REMARK 630 R45 A 306
REMARK 630 SOURCE: NULL
REMARK 630 TAXONOMY: NULL
REMARK 630 SUBCOMP: 14E GLU GLU NH2
REMARK 630 DETAILS: NULL
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 R45 A 306
REMARK 900
REMARK 900 RELATED ENTRIES
REMARK 900 RELATED ID: 4GR0 RELATED DB: PDB
REMARK 900 CRYSTAL STRUCTURE OF THE CATALYTIC DOMAIN OF HUMAN MMP12 IN COMPLEX
REMARK 900 WITH SELECTIVE PHOSPHINIC INHIBITOR RXP470B
REMARK 900 RELATED ID: 4GQL RELATED DB: PDB
REMARK 900 CRYSTAL STRUCTURE OF THE CATALYTIC DOMAIN OF HUMAN MMP12 IN COMPLEX
REMARK 900 WITH SELECTIVE PHOSPHINIC INHIBITOR RXP470.1
REMARK 900 RELATED ID: 3LIK RELATED DB: PDB
REMARK 900 HUMAN MMP12 IN COMPLEX WITH NON-ZINC CHELATING INHIBITOR
REMARK 900 RELATED ID: 3LJG RELATED DB: PDB
REMARK 900 HUMAN MMP12 IN COMPLEX WITH NON-ZINC CHELATING INHIBITOR
REMARK 900 RELATED ID: 3LIR RELATED DB: PDB
REMARK 900 HUMAN MMP12 IN COMPLEX WITH NON-ZINC CHELATING INHIBITOR
REMARK 900 RELATED ID: 3LIL RELATED DB: PDB
REMARK 900 HUMAN MMP12 IN COMPLEX WITH NON-ZINC CHELATING INHIBITOR
REMARK 900 RELATED ID: 4EFS 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: 3TS4 RELATED DB: PDB
REMARK 900 HUMAN MMP12 IN COMPLEX WITH L-GLUTAMATE MOTIF INHIBITOR
REMARK 900 RELATED ID: 4GR8 RELATED DB: PDB
DBREF 4GR3 A 106 263 UNP P39900 MMP12_HUMAN 106 263
SEQADV 4GR3 MET A 105 UNP P39900 INITIATING METHIONINE
SEQADV 4GR3 ASP A 171 UNP P39900 PHE 171 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 GLU 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 R45 A 306 45
HETNAM ZN ZINC ION
HETNAM CA CALCIUM ION
HETNAM R45 N-{(2S)-3-[(S)-(4-BROMOPHENYL)(HYDROXY)PHOSPHORYL]-2-
HETNAM 2 R45 [(3-PHENYL-1,2-OXAZOL-5-YL)METHYL]PROPANOYL}-L-ALPHA-
HETNAM 3 R45 GLUTAMYL-L-AL PHA-GLUTAMINE
HETSYN R45 RXP470A
FORMUL 2 ZN 2(ZN 2+)
FORMUL 4 CA 3(CA 2+)
FORMUL 7 R45 C29 H32 BR N4 O10 P
FORMUL 8 HOH *295(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 ASP A 244 PHE A 248 5 5
HELIX 4 4 SER A 251 TYR A 262 1 12
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 2.36
LINK OD1 ASP A 124 CA CA A 304 1555 1555 2.65
LINK O ASP A 158 CA CA A 303 1555 1555 2.31
LINK NE2 HIS A 168 ZN ZN A 302 1555 1555 2.00
LINK OD1 ASP A 170 ZN ZN A 302 1555 1555 1.92
LINK OD2 ASP A 175 CA CA A 305 1555 1555 2.37
LINK O GLY A 176 CA CA A 305 1555 1555 2.26
LINK O GLY A 178 CA CA A 305 1555 1555 2.32
LINK O ILE A 180 CA CA A 305 1555 1555 2.30
LINK NE2 HIS A 183 ZN ZN A 302 1555 1555 2.02
LINK O GLY A 190 CA CA A 303 1555 1555 2.26
LINK O GLY A 192 CA CA A 303 1555 1555 2.30
LINK OD2 ASP A 194 CA CA A 303 1555 1555 2.42
LINK ND1 HIS A 196 ZN ZN A 302 1555 1555 2.04
LINK OD1 ASP A 198 CA CA A 305 1555 1555 2.29
LINK O GLU A 199 CA CA A 304 1555 1555 2.36
LINK OE2 GLU A 199 CA CA A 304 1555 1555 2.38
LINK O GLU A 201 CA CA A 304 1555 1555 2.41
LINK OE2 GLU A 201 CA CA A 305 1555 1555 2.23
LINK NE2 HIS A 218 ZN ZN A 301 1555 1555 2.02
LINK NE2 HIS A 222 ZN ZN A 301 1555 1555 2.07
LINK NE2 HIS A 228 ZN ZN A 301 1555 1555 1.98
LINK ZN ZN A 301 O3 R45 A 306 1555 1555 1.91
LINK CA CA A 303 O HOH A 417 1555 1555 2.36
LINK CA CA A 303 O HOH A 424 1555 1555 2.43
LINK CA CA A 304 O HOH A 425 1555 1555 2.43
LINK CA CA A 304 O HOH A 437 1555 1555 2.38
SITE 1 AC1 4 HIS A 218 HIS A 222 HIS A 228 R45 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 417 HOH A 424
SITE 1 AC4 5 ASP A 124 GLU A 199 GLU A 201 HOH A 425
SITE 2 AC4 5 HOH A 437
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 29 THR A 154 GLY A 155 HIS A 172 GLY A 179
SITE 2 AC6 29 ILE A 180 LEU A 181 ALA A 182 HIS A 183
SITE 3 AC6 29 THR A 215 HIS A 218 GLU A 219 HIS A 222
SITE 4 AC6 29 HIS A 228 VAL A 235 PHE A 237 PRO A 238
SITE 5 AC6 29 THR A 239 TYR A 240 ZN A 301 HOH A 401
SITE 6 AC6 29 HOH A 422 HOH A 484 HOH A 497 HOH A 509
SITE 7 AC6 29 HOH A 512 HOH A 574 HOH A 578 HOH A 584
SITE 8 AC6 29 HOH A 657
CRYST1 68.960 63.130 37.310 90.00 90.00 90.00 P 21 21 2 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 0.014501 0.000000 0.000000 0.00000
SCALE2 0.000000 0.015840 0.000000 0.00000
SCALE3 0.000000 0.000000 0.026802 0.00000
(ATOM LINES ARE NOT SHOWN.)
END
