HEADER APOPTOSIS 18-DEC-18 6Q9U
TITLE HDMX (14-111; C17S) COMPLEXED WITH COMPOUND 12 AT 2.4A; STRUCTURAL
TITLE 2 STATES OF HDM2 AND HDMX: X-RAY ELUCIDATION OF ADAPTATIONS AND BINDING
TITLE 3 INTERACTIONS FOR DIFFERENT CHEMICAL COMPOUND CLASSES
COMPND MOL_ID: 1;
COMPND 2 MOLECULE: PROTEIN MDM4;
COMPND 3 CHAIN: A;
COMPND 4 FRAGMENT: N-TERMINAL DOMAIN, P53 BINDING DOMAIN;
COMPND 5 SYNONYM: DOUBLE MINUTE 4 PROTEIN,MDM2-LIKE P53-BINDING PROTEIN,
COMPND 6 PROTEIN MDMX,P53-BINDING PROTEIN MDM4;
COMPND 7 ENGINEERED: YES;
COMPND 8 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: MDM4, MDMX;
SOURCE 6 EXPRESSION_SYSTEM: ESCHERICHIA COLI BL21;
SOURCE 7 EXPRESSION_SYSTEM_TAXID: 511693;
SOURCE 8 EXPRESSION_SYSTEM_VECTOR_TYPE: PLASMID;
SOURCE 9 EXPRESSION_SYSTEM_PLASMID: PET28-DERIVED VECTOR
KEYWDS HDMX, MDM4, APOPTOSIS
EXPDTA X-RAY DIFFRACTION
AUTHOR J.KALLEN
REVDAT 4 24-JAN-24 6Q9U 1 REMARK
REVDAT 3 23-OCT-19 6Q9U 1 REMARK
REVDAT 2 24-JUL-19 6Q9U 1 JRNL
REVDAT 1 15-MAY-19 6Q9U 0
JRNL AUTH J.KALLEN,A.IZAAC,S.CHAU,E.WIRTH,J.SCHOEPFER,R.MAH,
JRNL AUTH 2 A.SCHLAPBACH,S.STUTZ,A.VAUPEL,V.GUAGNANO,K.MASUYA,
JRNL AUTH 3 T.M.STACHYRA,B.SALEM,P.CHENE,F.GESSIER,P.HOLZER,P.FURET
JRNL TITL STRUCTURAL STATES OF HDM2 AND HDMX: X-RAY ELUCIDATION OF
JRNL TITL 2 ADAPTATIONS AND BINDING INTERACTIONS FOR DIFFERENT CHEMICAL
JRNL TITL 3 COMPOUND CLASSES.
JRNL REF CHEMMEDCHEM V. 14 1305 2019
JRNL REFN ESSN 1860-7187
JRNL PMID 31066983
JRNL DOI 10.1002/CMDC.201900201
REMARK 2
REMARK 2 RESOLUTION. 2.40 ANGSTROMS.
REMARK 3
REMARK 3 REFINEMENT.
REMARK 3 PROGRAM : REFMAC
REMARK 3 AUTHORS : MURSHUDOV,SKUBAK,LEBEDEV,PANNU,STEINER,
REMARK 3 : NICHOLLS,WINN,LONG,VAGIN
REMARK 3
REMARK 3 DATA USED IN REFINEMENT.
REMARK 3 RESOLUTION RANGE HIGH (ANGSTROMS) : 2.40
REMARK 3 RESOLUTION RANGE LOW (ANGSTROMS) : 19.08
REMARK 3 DATA CUTOFF (SIGMA(F)) : 0.000
REMARK 3 COMPLETENESS FOR RANGE (%) : 100.0
REMARK 3 NUMBER OF REFLECTIONS : 4260
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) : 0.208
REMARK 3 R VALUE (WORKING SET) : 0.205
REMARK 3 FREE R VALUE : 0.265
REMARK 3 FREE R VALUE TEST SET SIZE (%) : 5.000
REMARK 3 FREE R VALUE TEST SET COUNT : 225
REMARK 3
REMARK 3 NUMBER OF NON-HYDROGEN ATOMS USED IN REFINEMENT.
REMARK 3 PROTEIN ATOMS : 689
REMARK 3 NUCLEIC ACID ATOMS : 0
REMARK 3 HETEROGEN ATOMS : 58
REMARK 3 SOLVENT ATOMS : 46
REMARK 3
REMARK 3 B VALUES.
REMARK 3 FROM WILSON PLOT (A**2) : 42.60
REMARK 3 MEAN B VALUE (OVERALL, A**2) : 37.98
REMARK 3 OVERALL ANISOTROPIC B VALUE.
REMARK 3 B11 (A**2) : -0.04000
REMARK 3 B22 (A**2) : -0.04000
REMARK 3 B33 (A**2) : 0.09000
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 OVERALL COORDINATE ERROR.
REMARK 3 ESU BASED ON R VALUE (A): 0.429
REMARK 3 ESU BASED ON FREE R VALUE (A): 0.280
REMARK 3 ESU BASED ON MAXIMUM LIKELIHOOD (A): 0.201
REMARK 3 ESU FOR B VALUES BASED ON MAXIMUM LIKELIHOOD (A**2): 8.957
REMARK 3
REMARK 3 RMS DEVIATIONS FROM IDEAL VALUES.
REMARK 3 DISTANCE RESTRAINTS. RMS SIGMA
REMARK 3 BOND LENGTH (A) : NULL ; NULL
REMARK 3 ANGLE DISTANCE (A) : NULL ; NULL
REMARK 3 INTRAPLANAR 1-4 DISTANCE (A) : NULL ; NULL
REMARK 3 H-BOND OR METAL COORDINATION (A) : NULL ; NULL
REMARK 3
REMARK 3 PLANE RESTRAINT (A) : NULL ; NULL
REMARK 3 CHIRAL-CENTER RESTRAINT (A**3) : NULL ; NULL
REMARK 3
REMARK 3 NON-BONDED CONTACT RESTRAINTS.
REMARK 3 SINGLE TORSION (A) : NULL ; NULL
REMARK 3 MULTIPLE TORSION (A) : NULL ; NULL
REMARK 3 H-BOND (X...Y) (A) : NULL ; NULL
REMARK 3 H-BOND (X-H...Y) (A) : NULL ; NULL
REMARK 3
REMARK 3 CONFORMATIONAL TORSION ANGLE RESTRAINTS.
REMARK 3 SPECIFIED (DEGREES) : NULL ; NULL
REMARK 3 PLANAR (DEGREES) : NULL ; NULL
REMARK 3 STAGGERED (DEGREES) : NULL ; NULL
REMARK 3 TRANSVERSE (DEGREES) : NULL ; NULL
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 OTHER REFINEMENT REMARKS: HYDROGENS HAVE BEEN ADDED IN THE RIDING
REMARK 3 POSITIONS U VALUES : REFINED INDIVIDUALLY
REMARK 4
REMARK 4 6Q9U COMPLIES WITH FORMAT V. 3.30, 13-JUL-11
REMARK 100
REMARK 100 THIS ENTRY HAS BEEN PROCESSED BY PDBE ON 18-DEC-18.
REMARK 100 THE DEPOSITION ID IS D_1200013525.
REMARK 200
REMARK 200 EXPERIMENTAL DETAILS
REMARK 200 EXPERIMENT TYPE : X-RAY DIFFRACTION
REMARK 200 DATE OF DATA COLLECTION : 21-JUN-12
REMARK 200 TEMPERATURE (KELVIN) : 100
REMARK 200 PH : 7.5
REMARK 200 NUMBER OF CRYSTALS USED : 1
REMARK 200
REMARK 200 SYNCHROTRON (Y/N) : Y
REMARK 200 RADIATION SOURCE : SLS
REMARK 200 BEAMLINE : X10SA
REMARK 200 X-RAY GENERATOR MODEL : NULL
REMARK 200 MONOCHROMATIC OR LAUE (M/L) : M
REMARK 200 WAVELENGTH OR RANGE (A) : 0.99983
REMARK 200 MONOCHROMATOR : SI 111 CHANNEL
REMARK 200 OPTICS : NULL
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 : XSCALE
REMARK 200
REMARK 200 NUMBER OF UNIQUE REFLECTIONS : 4485
REMARK 200 RESOLUTION RANGE HIGH (A) : 2.400
REMARK 200 RESOLUTION RANGE LOW (A) : 19.080
REMARK 200 REJECTION CRITERIA (SIGMA(I)) : NULL
REMARK 200
REMARK 200 OVERALL.
REMARK 200 COMPLETENESS FOR RANGE (%) : 99.7
REMARK 200 DATA REDUNDANCY : 6.500
REMARK 200 R MERGE (I) : 0.14100
REMARK 200 R SYM (I) : NULL
REMARK 200 <I/SIGMA(I)> FOR THE DATA SET : 8.5000
REMARK 200
REMARK 200 IN THE HIGHEST RESOLUTION SHELL.
REMARK 200 HIGHEST RESOLUTION SHELL, RANGE HIGH (A) : 2.40
REMARK 200 HIGHEST RESOLUTION SHELL, RANGE LOW (A) : 2.46
REMARK 200 COMPLETENESS FOR SHELL (%) : 99.7
REMARK 200 DATA REDUNDANCY IN SHELL : 6.10
REMARK 200 R MERGE FOR SHELL (I) : 0.34700
REMARK 200 R SYM FOR SHELL (I) : NULL
REMARK 200 <I/SIGMA(I)> FOR SHELL : 4.000
REMARK 200
REMARK 200 DIFFRACTION PROTOCOL: SINGLE WAVELENGTH
REMARK 200 METHOD USED TO DETERMINE THE STRUCTURE: MOLECULAR REPLACEMENT
REMARK 200 SOFTWARE USED: PHASER
REMARK 200 STARTING MODEL: 6Q9Q
REMARK 200
REMARK 200 REMARK: NULL
REMARK 280
REMARK 280 CRYSTAL
REMARK 280 SOLVENT CONTENT, VS (%): 52.17
REMARK 280 MATTHEWS COEFFICIENT, VM (ANGSTROMS**3/DA): 2.57
REMARK 280
REMARK 280 CRYSTALLIZATION CONDITIONS: 2.3M AMSO4, 2% W/V 18-CROWN-ETHER,
REMARK 280 0.1M HEPES, PH 7.5, VAPOR DIFFUSION, HANGING DROP, TEMPERATURE
REMARK 280 298K
REMARK 290
REMARK 290 CRYSTALLOGRAPHIC SYMMETRY
REMARK 290 SYMMETRY OPERATORS FOR SPACE GROUP: P 41
REMARK 290
REMARK 290 SYMOP SYMMETRY
REMARK 290 NNNMMM OPERATOR
REMARK 290 1555 X,Y,Z
REMARK 290 2555 -X,-Y,Z+1/2
REMARK 290 3555 -Y,X,Z+1/4
REMARK 290 4555 Y,-X,Z+3/4
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 27.91250
REMARK 290 SMTRY1 3 0.000000 -1.000000 0.000000 0.00000
REMARK 290 SMTRY2 3 1.000000 0.000000 0.000000 0.00000
REMARK 290 SMTRY3 3 0.000000 0.000000 1.000000 13.95625
REMARK 290 SMTRY1 4 0.000000 1.000000 0.000000 0.00000
REMARK 290 SMTRY2 4 -1.000000 0.000000 0.000000 0.00000
REMARK 290 SMTRY3 4 0.000000 0.000000 1.000000 41.86875
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 TOTAL BURIED SURFACE AREA: 90 ANGSTROM**2
REMARK 350 SURFACE AREA OF THE COMPLEX: 5590 ANGSTROM**2
REMARK 350 CHANGE IN SOLVENT FREE ENERGY: -5.0 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 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 GLY A 13
REMARK 465 PRO A 14
REMARK 465 ASP A 15
REMARK 465 SER A 16
REMARK 465 ALA A 17
REMARK 465 SER A 18
REMARK 465 ARG A 19
REMARK 465 ILE A 20
REMARK 465 SER A 21
REMARK 465 PRO A 22
REMARK 465 GLY A 23
REMARK 465 GLN A 24
REMARK 465 ALA A 111
REMARK 465 THR A 112
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 GLN A 65 56.76 38.69
REMARK 500 GLU A 71 88.46 -150.79
REMARK 500 PRO A 96 59.16 -103.85
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 HRE A 201
REMARK 800
REMARK 800 SITE_IDENTIFIER: AC2
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: binding site for residue O4B A 202
REMARK 800
REMARK 800 SITE_IDENTIFIER: AC3
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: binding site for residue CL A 203
REMARK 900
REMARK 900 RELATED ENTRIES
REMARK 900 RELATED ID: 6Q96 RELATED DB: PDB
DBREF 6Q9U A 15 112 UNP O15151 MDM4_HUMAN 14 111
SEQADV 6Q9U GLY A 13 UNP O15151 EXPRESSION TAG
SEQADV 6Q9U PRO A 14 UNP O15151 EXPRESSION TAG
SEQADV 6Q9U SER A 18 UNP O15151 CYS 17 ENGINEERED MUTATION
SEQRES 1 A 100 GLY PRO ASP SER ALA SER ARG ILE SER PRO GLY GLN ILE
SEQRES 2 A 100 ASN GLN VAL ARG PRO LYS LEU PRO LEU LEU LYS ILE LEU
SEQRES 3 A 100 HIS ALA ALA GLY ALA GLN GLY GLU MET PHE THR VAL LYS
SEQRES 4 A 100 GLU VAL MET HIS TYR LEU GLY GLN TYR ILE MET VAL LYS
SEQRES 5 A 100 GLN LEU TYR ASP GLN GLN GLU GLN HIS MET VAL TYR CYS
SEQRES 6 A 100 GLY GLY ASP LEU LEU GLY GLU LEU LEU GLY ARG GLN SER
SEQRES 7 A 100 PHE SER VAL LYS ASP PRO SER PRO LEU TYR ASP MET LEU
SEQRES 8 A 100 ARG LYS ASN LEU VAL THR LEU ALA THR
HET HRE A 201 39
HET O4B A 202 18
HET CL A 203 1
HETNAM HRE 4-[(4~{S})-5-(5-CHLORANYL-2-OXIDANYLIDENE-1~{H}-
HETNAM 2 HRE PYRIDIN-3-YL)-2-[2-(DIMETHYLAMINO)-4-METHOXY-
HETNAM 3 HRE PYRIMIDIN-5-YL]-6-OXIDANYLIDENE-3-PROPAN-2-YL-4~{H}-
HETNAM 4 HRE PYRROLO[3,4-C]PYRAZOL-4-YL]BENZENECARBONITRILE
HETNAM O4B 1,4,7,10,13,16-HEXAOXACYCLOOCTADECANE
HETNAM CL CHLORIDE ION
FORMUL 2 HRE C27 H25 CL N8 O3
FORMUL 3 O4B C12 H24 O6
FORMUL 4 CL CL 1-
FORMUL 5 HOH *46(H2 O)
HELIX 1 AA1 LYS A 31 ALA A 41 1 11
HELIX 2 AA2 VAL A 50 LYS A 64 1 15
HELIX 3 AA3 ASP A 80 GLY A 87 1 8
HELIX 4 AA4 PRO A 96 ASN A 106 1 11
SHEET 1 AA1 3 PHE A 48 THR A 49 0
SHEET 2 AA1 3 GLN A 27 PRO A 30 -1 N VAL A 28 O PHE A 48
SHEET 3 AA1 3 LEU A 107 THR A 109 -1 O VAL A 108 N ARG A 29
SHEET 1 AA2 3 TYR A 67 ASP A 68 0
SHEET 2 AA2 3 GLU A 71 TYR A 76 -1 O MET A 74 N ASP A 68
SHEET 3 AA2 3 SER A 90 SER A 92 -1 O PHE A 91 N VAL A 75
SITE 1 AC1 11 MET A 54 HIS A 55 GLY A 58 GLN A 59
SITE 2 AC1 11 ILE A 61 TYR A 67 GLN A 72 VAL A 93
SITE 3 AC1 11 PRO A 96 LEU A 99 TYR A 100
SITE 1 AC2 7 ILE A 25 VAL A 28 ALA A 40 VAL A 50
SITE 2 AC2 7 VAL A 63 LYS A 64 THR A 109
SITE 1 AC3 2 TYR A 56 GLN A 59
CRYST1 45.403 45.403 55.825 90.00 90.00 90.00 P 41 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 0.022025 0.000000 0.000000 0.00000
SCALE2 0.000000 0.022025 0.000000 0.00000
SCALE3 0.000000 0.000000 0.017913 0.00000
(ATOM LINES ARE NOT SHOWN.)
END
