HEADER HYDROLASE 26-JUL-06 2HU6
TITLE CRYSTAL STRUCTURE OF HUMAN MMP-12 IN COMPLEX WITH ACETOHYDROXAMIC ACID
TITLE 2 AND A BICYCLIC INHIBITOR
COMPND MOL_ID: 1;
COMPND 2 MOLECULE: MACROPHAGE METALLOELASTASE;
COMPND 3 CHAIN: A;
COMPND 4 FRAGMENT: CATALYTIC DOMAIN (RESIDUES 106-263);
COMPND 5 SYNONYM: HME, MATRIX METALLOPROTEINASE-12, MMP-12, MACROPHAGE
COMPND 6 ELASTASE, ME;
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: MMP12, HME;
SOURCE 6 EXPRESSION_SYSTEM: ESCHERICHIA COLI BL21;
SOURCE 7 EXPRESSION_SYSTEM_TAXID: 511693;
SOURCE 8 EXPRESSION_SYSTEM_STRAIN: BL21;
SOURCE 9 EXPRESSION_SYSTEM_VECTOR_TYPE: PLASMID;
SOURCE 10 EXPRESSION_SYSTEM_PLASMID: PET21
KEYWDS MMP-12, MATRIX METALLOPROTEINASE, MACROPHAGE METALLOELASTASE,
KEYWDS 2 INHIBITOR, HYDROXAMIC ACID, DRUG DESIGN, HYDROLASE
EXPDTA X-RAY DIFFRACTION
AUTHOR C.MANNINO,M.NIEVO,F.MACHETTI,A.PAPAKYRIAKOU,V.CALDERONE,M.FRAGAI,
AUTHOR 2 A.GUARNA
REVDAT 6 30-AUG-23 2HU6 1 REMARK
REVDAT 5 20-OCT-21 2HU6 1 REMARK SEQADV LINK
REVDAT 4 24-JAN-18 2HU6 1 JRNL
REVDAT 3 18-OCT-17 2HU6 1 REMARK
REVDAT 2 24-FEB-09 2HU6 1 VERSN
REVDAT 1 19-DEC-06 2HU6 0
JRNL AUTH C.MANNINO,M.NIEVO,F.MACHETTI,A.PAPAKYRIAKOU,V.CALDERONE,
JRNL AUTH 2 M.FRAGAI,A.GUARNA
JRNL TITL SYNTHESIS OF BICYCLIC MOLECULAR SCAFFOLDS (BTAA): AN
JRNL TITL 2 INVESTIGATION TOWARDS NEW SELECTIVE MMP-12 INHIBITORS.
JRNL REF BIOORG.MED.CHEM. V. 14 7392 2006
JRNL REFN ISSN 0968-0896
JRNL PMID 16899369
JRNL DOI 10.1016/J.BMC.2006.07.028
REMARK 1
REMARK 1 REFERENCE 1
REMARK 1 AUTH I.BERTINI,V.CALDERONE,M.COSENZA,M.FRAGAI,Y.-M.LEE,
REMARK 1 AUTH 2 C.LUCHINAT,S.MANGANI,P.TURANO
REMARK 1 TITL CONFORMATIONAL VARIABILITY OF MATRIX METALLOPROTEINASES:
REMARK 1 TITL 2 BEYOND A SINGLE 3D STRUCTURE.
REMARK 1 REF PROC.NATL.ACAD.SCI.USA V. 102 5334 2005
REMARK 1 REFN ISSN 0027-8424
REMARK 2
REMARK 2 RESOLUTION. 1.32 ANGSTROMS.
REMARK 3
REMARK 3 REFINEMENT.
REMARK 3 PROGRAM : REFMAC 5.2.0019
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) : 1.32
REMARK 3 RESOLUTION RANGE LOW (ANGSTROMS) : 25.68
REMARK 3 DATA CUTOFF (SIGMA(F)) : 0.000
REMARK 3 COMPLETENESS FOR RANGE (%) : 100.0
REMARK 3 NUMBER OF REFLECTIONS : 31503
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) : 0.163
REMARK 3 R VALUE (WORKING SET) : 0.161
REMARK 3 FREE R VALUE : 0.182
REMARK 3 FREE R VALUE TEST SET SIZE (%) : 9.100
REMARK 3 FREE R VALUE TEST SET COUNT : 3144
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) : 1.32
REMARK 3 BIN RESOLUTION RANGE LOW (A) : 1.35
REMARK 3 REFLECTION IN BIN (WORKING SET) : 2119
REMARK 3 BIN COMPLETENESS (WORKING+TEST) (%) : 100.0
REMARK 3 BIN R VALUE (WORKING SET) : 0.2290
REMARK 3 BIN FREE R VALUE SET COUNT : 220
REMARK 3 BIN FREE R VALUE : 0.2850
REMARK 3
REMARK 3 NUMBER OF NON-HYDROGEN ATOMS USED IN REFINEMENT.
REMARK 3 PROTEIN ATOMS : 1238
REMARK 3 NUCLEIC ACID ATOMS : 0
REMARK 3 HETEROGEN ATOMS : 38
REMARK 3 SOLVENT ATOMS : 256
REMARK 3
REMARK 3 B VALUES.
REMARK 3 FROM WILSON PLOT (A**2) : 10.41
REMARK 3 MEAN B VALUE (OVERALL, A**2) : 13.58
REMARK 3 OVERALL ANISOTROPIC B VALUE.
REMARK 3 B11 (A**2) : 0.27000
REMARK 3 B22 (A**2) : -0.11000
REMARK 3 B33 (A**2) : -0.44000
REMARK 3 B12 (A**2) : 0.00000
REMARK 3 B13 (A**2) : -0.33000
REMARK 3 B23 (A**2) : 0.00000
REMARK 3
REMARK 3 ESTIMATED OVERALL COORDINATE ERROR.
REMARK 3 ESU BASED ON R VALUE (A): 0.064
REMARK 3 ESU BASED ON FREE R VALUE (A): 0.055
REMARK 3 ESU BASED ON MAXIMUM LIKELIHOOD (A): 0.030
REMARK 3 ESU FOR B VALUES BASED ON MAXIMUM LIKELIHOOD (A**2): 1.570
REMARK 3
REMARK 3 CORRELATION COEFFICIENTS.
REMARK 3 CORRELATION COEFFICIENT FO-FC : 0.965
REMARK 3 CORRELATION COEFFICIENT FO-FC FREE : 0.956
REMARK 3
REMARK 3 RMS DEVIATIONS FROM IDEAL VALUES COUNT RMS WEIGHT
REMARK 3 BOND LENGTHS REFINED ATOMS (A): 1310 ; 0.006 ; 0.021
REMARK 3 BOND LENGTHS OTHERS (A): NULL ; NULL ; NULL
REMARK 3 BOND ANGLES REFINED ATOMS (DEGREES): 1777 ; 1.100 ; 1.943
REMARK 3 BOND ANGLES OTHERS (DEGREES): NULL ; NULL ; NULL
REMARK 3 TORSION ANGLES, PERIOD 1 (DEGREES): 157 ; 5.720 ; 5.000
REMARK 3 TORSION ANGLES, PERIOD 2 (DEGREES): 63 ;33.449 ;23.175
REMARK 3 TORSION ANGLES, PERIOD 3 (DEGREES): 188 ; 9.330 ;15.000
REMARK 3 TORSION ANGLES, PERIOD 4 (DEGREES): 7 ;16.790 ;15.000
REMARK 3 CHIRAL-CENTER RESTRAINTS (A**3): 181 ; 0.077 ; 0.200
REMARK 3 GENERAL PLANES REFINED ATOMS (A): 1042 ; 0.004 ; 0.020
REMARK 3 GENERAL PLANES OTHERS (A): NULL ; NULL ; NULL
REMARK 3 NON-BONDED CONTACTS REFINED ATOMS (A): 669 ; 0.183 ; 0.200
REMARK 3 NON-BONDED CONTACTS OTHERS (A): NULL ; NULL ; NULL
REMARK 3 NON-BONDED TORSION REFINED ATOMS (A): 923 ; 0.308 ; 0.200
REMARK 3 NON-BONDED TORSION OTHERS (A): NULL ; NULL ; NULL
REMARK 3 H-BOND (X...Y) REFINED ATOMS (A): 150 ; 0.115 ; 0.200
REMARK 3 H-BOND (X...Y) OTHERS (A): NULL ; NULL ; NULL
REMARK 3 POTENTIAL METAL-ION REFINED ATOMS (A): 18 ; 0.074 ; 0.200
REMARK 3 POTENTIAL METAL-ION OTHERS (A): NULL ; NULL ; NULL
REMARK 3 SYMMETRY VDW REFINED ATOMS (A): 68 ; 0.202 ; 0.200
REMARK 3 SYMMETRY VDW OTHERS (A): NULL ; NULL ; NULL
REMARK 3 SYMMETRY H-BOND REFINED ATOMS (A): 37 ; 0.121 ; 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): 796 ; 0.760 ; 1.500
REMARK 3 MAIN-CHAIN BOND OTHER ATOMS (A**2): NULL ; NULL ; NULL
REMARK 3 MAIN-CHAIN ANGLE REFINED ATOMS (A**2): 1242 ; 1.115 ; 2.000
REMARK 3 MAIN-CHAIN ANGLE OTHER ATOMS (A**2): NULL ; NULL ; NULL
REMARK 3 SIDE-CHAIN BOND REFINED ATOMS (A**2): 588 ; 1.837 ; 3.000
REMARK 3 SIDE-CHAIN BOND OTHER ATOMS (A**2): NULL ; NULL ; NULL
REMARK 3 SIDE-CHAIN ANGLE REFINED ATOMS (A**2): 535 ; 2.348 ; 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): 1384 ; 1.751 ; 3.000
REMARK 3 SPHERICITY; FREE ATOMS (A**2): 262 ; 2.614 ; 3.000
REMARK 3 SPHERICITY; BONDED ATOMS (A**2): 1271 ; 1.860 ; 3.000
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 2HU6 COMPLIES WITH FORMAT V. 3.30, 13-JUL-11
REMARK 100
REMARK 100 THIS ENTRY HAS BEEN PROCESSED BY RCSB ON 04-AUG-06.
REMARK 100 THE DEPOSITION ID IS D_1000038765.
REMARK 200
REMARK 200 EXPERIMENTAL DETAILS
REMARK 200 EXPERIMENT TYPE : X-RAY DIFFRACTION
REMARK 200 DATE OF DATA COLLECTION : 26-JUL-05
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 : EMBL/DESY, HAMBURG
REMARK 200 BEAMLINE : BW7A
REMARK 200 X-RAY GENERATOR MODEL : NULL
REMARK 200 MONOCHROMATIC OR LAUE (M/L) : M
REMARK 200 WAVELENGTH OR RANGE (A) : 0.93920
REMARK 200 MONOCHROMATOR : FIXED EXIT DOUBLE CRYSTAL SI
REMARK 200 [111], HORIZONTALLY FOCUSING
REMARK 200 OPTICS : FIXED EXIT DOUBLE CRYSTAL SI
REMARK 200 [111], HORIZONTALLY FOCUSING
REMARK 200
REMARK 200 DETECTOR TYPE : CCD
REMARK 200 DETECTOR MANUFACTURER : MAR CCD 165 MM
REMARK 200 INTENSITY-INTEGRATION SOFTWARE : MOSFLM
REMARK 200 DATA SCALING SOFTWARE : CCP4 (SCALA)
REMARK 200
REMARK 200 NUMBER OF UNIQUE REFLECTIONS : 34648
REMARK 200 RESOLUTION RANGE HIGH (A) : 1.320
REMARK 200 RESOLUTION RANGE LOW (A) : 49.080
REMARK 200 REJECTION CRITERIA (SIGMA(I)) : 0.000
REMARK 200
REMARK 200 OVERALL.
REMARK 200 COMPLETENESS FOR RANGE (%) : 99.1
REMARK 200 DATA REDUNDANCY : 3.100
REMARK 200 R MERGE (I) : 0.05300
REMARK 200 R SYM (I) : 0.05300
REMARK 200 <I/SIGMA(I)> FOR THE DATA SET : 8.6000
REMARK 200
REMARK 200 IN THE HIGHEST RESOLUTION SHELL.
REMARK 200 HIGHEST RESOLUTION SHELL, RANGE HIGH (A) : 1.32
REMARK 200 HIGHEST RESOLUTION SHELL, RANGE LOW (A) : 1.39
REMARK 200 COMPLETENESS FOR SHELL (%) : 95.6
REMARK 200 DATA REDUNDANCY IN SHELL : 2.90
REMARK 200 R MERGE FOR SHELL (I) : 0.28200
REMARK 200 R SYM FOR SHELL (I) : 0.28200
REMARK 200 <I/SIGMA(I)> FOR SHELL : 2.100
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: PDB ENTRY 1Y93
REMARK 200
REMARK 200 REMARK: NULL
REMARK 280
REMARK 280 CRYSTAL
REMARK 280 SOLVENT CONTENT, VS (%): 42.72
REMARK 280 MATTHEWS COEFFICIENT, VM (ANGSTROMS**3/DA): 2.15
REMARK 280
REMARK 280 CRYSTALLIZATION CONDITIONS: 0.1 M TRIS-HCL, 30% PEG 6000, PH 8.0,
REMARK 280 VAPOR DIFFUSION, SITTING DROP, TEMPERATURE 298K
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 25.62500
REMARK 290 SMTRY2 3 0.000000 1.000000 0.000000 30.08950
REMARK 290 SMTRY3 3 0.000000 0.000000 1.000000 0.00000
REMARK 290 SMTRY1 4 -1.000000 0.000000 0.000000 25.62500
REMARK 290 SMTRY2 4 0.000000 1.000000 0.000000 30.08950
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 PROTEIN IS MONOMERIC IN VIVO AND THERE IS ONE MOLECULE
REMARK 300 IN THE ASYMMETRIC UNIT.
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 480 LIES ON A SPECIAL POSITION.
REMARK 375 HOH A 483 LIES ON A SPECIAL POSITION.
REMARK 375 HOH A 500 LIES ON A SPECIAL POSITION.
REMARK 375 HOH A 543 LIES ON A SPECIAL POSITION.
REMARK 375 HOH A 617 LIES ON A SPECIAL POSITION.
REMARK 465
REMARK 465 MISSING RESIDUES
REMARK 465 THE FOLLOWING RESIDUES WERE NOT LOCATED IN THE
REMARK 465 EXPERIMENT. (M=MODEL NUMBER; RES=RESIDUE NAME; C=CHAIN
REMARK 465 IDENTIFIER; SSSEQ=SEQUENCE NUMBER; I=INSERTION CODE.)
REMARK 465
REMARK 465 M RES C SSSEQI
REMARK 465 MET A 105
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 168 26.32 -140.42
REMARK 500 ASP A 171 -1.25 75.88
REMARK 500 HIS A 172 72.62 -111.42
REMARK 500 HIS A 206 -153.24 -137.60
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 267 CA
REMARK 620 N RES CSSEQI ATOM
REMARK 620 1 ASP A 124 OD1
REMARK 620 2 ASP A 124 OD2 51.9
REMARK 620 3 GLU A 199 O 162.6 137.7
REMARK 620 4 GLU A 199 OE2 86.1 85.6 81.1
REMARK 620 5 GLU A 201 O 120.8 75.5 76.0 118.0
REMARK 620 6 HOH A 410 O 85.0 136.6 82.5 86.4 143.7
REMARK 620 7 HOH A 428 O 89.2 103.4 100.0 164.1 77.4 78.0
REMARK 620 N 1 2 3 4 5 6
REMARK 620
REMARK 620 COORDINATION ANGLES FOR: M RES CSSEQI METAL
REMARK 620 CA A 266 CA
REMARK 620 N RES CSSEQI ATOM
REMARK 620 1 ASP A 158 O
REMARK 620 2 GLY A 190 O 164.8
REMARK 620 3 GLY A 192 O 83.8 97.0
REMARK 620 4 ASP A 194 OD2 90.4 104.7 92.5
REMARK 620 5 HOH A 405 O 81.1 84.3 76.2 166.5
REMARK 620 6 HOH A 470 O 93.8 83.2 171.6 95.6 95.5
REMARK 620 N 1 2 3 4 5
REMARK 620
REMARK 620 COORDINATION ANGLES FOR: M RES CSSEQI METAL
REMARK 620 ZN A 265 ZN
REMARK 620 N RES CSSEQI ATOM
REMARK 620 1 HIS A 168 NE2
REMARK 620 2 ASP A 170 OD2 109.6
REMARK 620 3 HIS A 183 NE2 117.3 112.5
REMARK 620 4 HIS A 196 ND1 107.3 95.6 112.3
REMARK 620 N 1 2 3
REMARK 620
REMARK 620 COORDINATION ANGLES FOR: M RES CSSEQI METAL
REMARK 620 CA A 268 CA
REMARK 620 N RES CSSEQI ATOM
REMARK 620 1 ASP A 175 OD2
REMARK 620 2 GLY A 176 O 86.7
REMARK 620 3 GLY A 178 O 86.5 87.1
REMARK 620 4 ILE A 180 O 90.4 177.0 92.5
REMARK 620 5 ASP A 198 OD1 93.1 88.6 175.7 91.8
REMARK 620 6 GLU A 201 OE2 175.7 94.4 89.4 88.5 91.0
REMARK 620 N 1 2 3 4 5
REMARK 620
REMARK 620 COORDINATION ANGLES FOR: M RES CSSEQI METAL
REMARK 620 ZN A 264 ZN
REMARK 620 N RES CSSEQI ATOM
REMARK 620 1 HIS A 218 NE2
REMARK 620 2 HIS A 222 NE2 95.7
REMARK 620 3 HIS A 228 NE2 101.1 96.8
REMARK 620 4 HAE A 269 O2 153.3 108.7 87.0
REMARK 620 5 HAE A 269 O 96.5 95.7 157.3 71.1
REMARK 620 6 HOH A 655 O 80.7 169.2 74.0 77.1 94.9
REMARK 620 N 1 2 3 4 5
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 264
REMARK 800
REMARK 800 SITE_IDENTIFIER: AC2
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: BINDING SITE FOR RESIDUE ZN A 265
REMARK 800
REMARK 800 SITE_IDENTIFIER: AC3
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: BINDING SITE FOR RESIDUE CA A 266
REMARK 800
REMARK 800 SITE_IDENTIFIER: AC4
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: BINDING SITE FOR RESIDUE CA A 267
REMARK 800
REMARK 800 SITE_IDENTIFIER: AC5
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: BINDING SITE FOR RESIDUE CA A 268
REMARK 800
REMARK 800 SITE_IDENTIFIER: AC6
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: BINDING SITE FOR RESIDUE 37A A 400
REMARK 800
REMARK 800 SITE_IDENTIFIER: AC7
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: BINDING SITE FOR RESIDUE HAE A 269
REMARK 900
REMARK 900 RELATED ENTRIES
REMARK 900 RELATED ID: 1Y93 RELATED DB: PDB
REMARK 900 CRYSTAL STRUCTURE OF THE CATALYTIC DOMAIN OF HUMAN MMP12 COMPLEXED
REMARK 900 WITH ACETOHYDROXAMIC ACID AT ATOMIC RESOLUTION.
REMARK 900 RELATED ID: 1RMZ RELATED DB: PDB
REMARK 900 CRYSTAL STRUCTURE OF THE CATALYTIC DOMAIN OF HUMAN MMP12 COMPLEXED
REMARK 900 WITH THE INHIBITOR NNGH AT 1.3 A RESOLUTION.
DBREF 2HU6 A 106 263 UNP P39900 MMP12_HUMAN 106 263
SEQADV 2HU6 MET A 105 UNP P39900 INITIATING METHIONINE
SEQADV 2HU6 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 264 1
HET ZN A 265 1
HET CA A 266 1
HET CA A 267 1
HET CA A 268 1
HET 37A A 400 28
HET HAE A 269 5
HETNAM ZN ZINC ION
HETNAM CA CALCIUM ION
HETNAM 37A (1S,5S,7R)-N~7~-(BIPHENYL-4-YLMETHYL)-N~3~-HYDROXY-6,8-
HETNAM 2 37A DIOXA-3-AZABICYCLO[3.2.1]OCTANE-3,7-DICARBOXAMIDE
HETNAM HAE ACETOHYDROXAMIC ACID
HETSYN 37A (1S,5S,7R)-3-AZA-6,8-DIOXA-BICYCLO[3.2.1]OCTANE-3,7-
HETSYN 2 37A DICARBOXYLIC ACID 7-[(BIPHENYL-4-YLMETHYL)-AMIDE]-3-
HETSYN 3 37A HYDROXYAMIDE
FORMUL 2 ZN 2(ZN 2+)
FORMUL 4 CA 3(CA 2+)
FORMUL 7 37A C20 H21 N3 O5
FORMUL 8 HAE C2 H5 N O2
FORMUL 9 HOH *256(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 OD1 ASP A 124 CA CA A 267 1555 1555 2.57
LINK OD2 ASP A 124 CA CA A 267 1555 1555 2.41
LINK O ASP A 158 CA CA A 266 1555 1555 2.46
LINK NE2 HIS A 168 ZN ZN A 265 1555 1555 2.03
LINK OD2 ASP A 170 ZN ZN A 265 1555 1555 1.97
LINK OD2 ASP A 175 CA CA A 268 1555 1555 2.35
LINK O GLY A 176 CA CA A 268 1555 1555 2.28
LINK O GLY A 178 CA CA A 268 1555 1555 2.35
LINK O ILE A 180 CA CA A 268 1555 1555 2.30
LINK NE2 HIS A 183 ZN ZN A 265 1555 1555 2.03
LINK O GLY A 190 CA CA A 266 1555 1555 2.41
LINK O GLY A 192 CA CA A 266 1555 1555 2.34
LINK OD2 ASP A 194 CA CA A 266 1555 1555 2.54
LINK ND1 HIS A 196 ZN ZN A 265 1555 1555 2.06
LINK OD1 ASP A 198 CA CA A 268 1555 1555 2.37
LINK O GLU A 199 CA CA A 267 1555 1555 2.35
LINK OE2 GLU A 199 CA CA A 267 1555 1555 2.39
LINK O GLU A 201 CA CA A 267 1555 1555 2.44
LINK OE2 GLU A 201 CA CA A 268 1555 1555 2.26
LINK NE2 HIS A 218 ZN ZN A 264 1555 1555 2.10
LINK NE2 HIS A 222 ZN ZN A 264 1555 1555 2.13
LINK NE2 HIS A 228 ZN ZN A 264 1555 1555 2.11
LINK ZN ZN A 264 O2 HAE A 269 1555 1555 2.38
LINK ZN ZN A 264 O HAE A 269 1555 1555 2.14
LINK ZN ZN A 264 O HOH A 655 1555 1555 2.44
LINK CA CA A 266 O HOH A 405 1555 1555 2.51
LINK CA CA A 266 O HOH A 470 1555 1555 2.39
LINK CA CA A 267 O HOH A 410 1555 1555 2.41
LINK CA CA A 267 O HOH A 428 1555 1555 2.32
SITE 1 AC1 5 HIS A 218 HIS A 222 HIS A 228 HAE A 269
SITE 2 AC1 5 HOH A 655
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 405 HOH A 470
SITE 1 AC4 5 ASP A 124 GLU A 199 GLU A 201 HOH A 410
SITE 2 AC4 5 HOH A 428
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 17 GLY A 179 ILE A 180 LEU A 181 ALA A 182
SITE 2 AC6 17 HIS A 218 VAL A 235 PHE A 237 PRO A 238
SITE 3 AC6 17 THR A 239 TYR A 240 LYS A 241 HOH A 446
SITE 4 AC6 17 HOH A 460 HOH A 468 HOH A 474 HOH A 535
SITE 5 AC6 17 HOH A 656
SITE 1 AC7 7 ALA A 182 HIS A 218 GLU A 219 HIS A 222
SITE 2 AC7 7 HIS A 228 ZN A 264 HOH A 655
CRYST1 51.250 60.179 53.974 90.00 114.59 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 0.019512 0.000000 0.008929 0.00000
SCALE2 0.000000 0.016617 0.000000 0.00000
SCALE3 0.000000 0.000000 0.020375 0.00000
(ATOM LINES ARE NOT SHOWN.)
END
