HEADER LIGASE 23-JUN-04 1TTV
TITLE NMR STRUCTURE OF A COMPLEX BETWEEN MDM2 AND A SMALL
TITLE 2 MOLECULE INHIBITOR
COMPND MOL_ID: 1;
COMPND 2 MOLECULE: UBIQUITIN-PROTEIN LIGASE E3 MDM2;
COMPND 3 CHAIN: A;
COMPND 4 FRAGMENT: RESIUDES 13-119;
COMPND 5 SYNONYM: P53-BINDING PROTEIN MDM2, DOUBLE MINUTE 2 PROTEIN,
COMPND 6 XDM2;
COMPND 7 EC: 6.3.2.-;
COMPND 8 ENGINEERED: YES;
COMPND 9 MUTATION: YES
SOURCE MOL_ID: 1;
SOURCE 2 ORGANISM_SCIENTIFIC: XENOPUS LAEVIS;
SOURCE 3 ORGANISM_COMMON: AFRICAN CLAWED FROG;
SOURCE 4 ORGANISM_TAXID: 8355;
SOURCE 5 GENE: MDM2;
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: PUBS 520
KEYWDS MDM2, PROTEIN-PROTEIN INTERACTION, LIGASE
EXPDTA SOLUTION NMR
NUMMDL 18
AUTHOR D.C.FRY,S.D.EMERSON,S.PALME,B.T.VU,C.M.LIU,F.PODLASKI
REVDAT 2 24-FEB-09 1TTV 1 VERSN
REVDAT 1 04-JAN-05 1TTV 0
JRNL AUTH D.C.FRY,S.D.EMERSON,S.PALME,B.T.VU,C.M.LIU,
JRNL AUTH 2 F.PODLASKI
JRNL TITL NMR STRUCTURE OF A COMPLEX BETWEEN MDM2 AND A
JRNL TITL 2 SMALL MOLECULE INHIBITOR.
JRNL REF J.BIOMOL.NMR V. 30 163 2004
JRNL REFN ISSN 0925-2738
JRNL PMID 15557803
JRNL DOI 10.1023/B:JNMR.0000048856.84603.9B
REMARK 1
REMARK 2
REMARK 2 RESOLUTION. NOT APPLICABLE.
REMARK 3
REMARK 3 REFINEMENT.
REMARK 3 PROGRAM : CNX 2000.1
REMARK 3 AUTHORS : BRUNGER ET AL.
REMARK 3
REMARK 3 OTHER REFINEMENT REMARKS: STRUCTURE CALCULATIONS UTILIZED 1169
REMARK 3 NOE-BASED DISTANCE CONSTRAINTS, OF WHICH 54 WERE
REMARK 3 INTERMOLECULAR; 176 DIHEDRAL ANGLE CONSTRAINTS; AND 48
REMARK 3 HYDROGEN BOND CONSTRAINTS. THE PIPERAZINYL MOIETY OF THE
REMARK 3 INHIBITOR GAVE NO NOES, HENCE THE POSITIONS OF ITS ATOMS ARE
REMARK 3 NOT KNOWN AND THE STEREOCHEMISTRY IS NOT RIGOROUSLY
REMARK 3 ESTABLISHED.
REMARK 4
REMARK 4 1TTV COMPLIES WITH FORMAT V. 3.15, 01-DEC-08
REMARK 100
REMARK 100 THIS ENTRY HAS BEEN PROCESSED BY RCSB ON 25-JUN-04.
REMARK 100 THE RCSB ID CODE IS RCSB022895.
REMARK 210
REMARK 210 EXPERIMENTAL DETAILS
REMARK 210 EXPERIMENT TYPE : NMR
REMARK 210 TEMPERATURE (KELVIN) : 293
REMARK 210 PH : 7.0
REMARK 210 IONIC STRENGTH : 50MM D13-MES; 150MM KCL; 50MM
REMARK 210 D10-DTT; 1.5MM NAN3
REMARK 210 PRESSURE : AMBIENT
REMARK 210 SAMPLE CONTENTS : 0.6MM 13C/15N-MDM2; 3.5MM
REMARK 210 INHIBITOR; 50MM D13-MES; 150MM
REMARK 210 KCL; 50MM D10-DTT; 1.5MM NAN3
REMARK 210
REMARK 210 NMR EXPERIMENTS CONDUCTED : 3D_15N-SEPARATED_NOESY, 3D_
REMARK 210 13C-SEPARATED_NOESY, 2D 13C/
REMARK 210 15N-FILTERED NOESY
REMARK 210 SPECTROMETER FIELD STRENGTH : 600 MHZ
REMARK 210 SPECTROMETER MODEL : INOVA
REMARK 210 SPECTROMETER MANUFACTURER : VARIAN
REMARK 210
REMARK 210 STRUCTURE DETERMINATION.
REMARK 210 SOFTWARE USED : FELIX 2000, NMRVIEW 5.0.3,
REMARK 210 CNX 2000.1
REMARK 210 METHOD USED : SIMULATED ANNEALING
REMARK 210
REMARK 210 CONFORMERS, NUMBER CALCULATED : 42
REMARK 210 CONFORMERS, NUMBER SUBMITTED : 18
REMARK 210 CONFORMERS, SELECTION CRITERIA : STRUCTURES WITH ACCEPTABLE
REMARK 210 COVALENT GEOMETRY,STRUCTURES
REMARK 210 WITH THE LEAST RESTRAINT
REMARK 210 VIOLATIONS
REMARK 210
REMARK 210 BEST REPRESENTATIVE CONFORMER IN THIS ENSEMBLE : 4
REMARK 210
REMARK 210 REMARK: NULL
REMARK 215
REMARK 215 NMR STUDY
REMARK 215 THE COORDINATES IN THIS ENTRY WERE GENERATED FROM SOLUTION
REMARK 215 NMR DATA. PROTEIN DATA BANK CONVENTIONS REQUIRE THAT
REMARK 215 CRYST1 AND SCALE RECORDS BE INCLUDED, BUT THE VALUES ON
REMARK 215 THESE RECORDS ARE MEANINGLESS.
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 1 SER A 16 -74.65 -173.05
REMARK 500 1 THR A 17 -58.95 -165.12
REMARK 500 1 ASP A 19 26.99 -158.29
REMARK 500 1 LYS A 41 179.85 -51.77
REMARK 500 1 GLN A 61 63.16 71.87
REMARK 500 1 LYS A 66 -78.52 -46.49
REMARK 500 1 GLU A 86 129.57 179.35
REMARK 500 2 ILE A 15 -42.96 -148.22
REMARK 500 2 SER A 16 -66.23 70.08
REMARK 500 2 GLU A 21 -166.12 -106.85
REMARK 500 2 GLN A 61 62.18 69.77
REMARK 500 2 ASN A 102 32.23 -96.12
REMARK 500 2 GLU A 110 163.88 60.83
REMARK 500 3 SER A 16 -75.06 -166.72
REMARK 500 3 THR A 17 -67.47 -163.60
REMARK 500 3 GLU A 21 -163.37 -117.39
REMARK 500 3 THR A 27 158.94 -48.65
REMARK 500 3 LYS A 41 177.52 -52.19
REMARK 500 3 GLN A 61 60.25 72.01
REMARK 500 3 ASN A 102 37.96 -95.63
REMARK 500 3 VAL A 104 -82.83 -53.35
REMARK 500 4 ILE A 15 -77.05 64.57
REMARK 500 4 SER A 16 -80.66 61.52
REMARK 500 4 ASP A 19 135.28 63.83
REMARK 500 4 GLU A 21 -81.75 -145.38
REMARK 500 4 THR A 27 162.07 -49.20
REMARK 500 4 LYS A 41 176.15 -49.15
REMARK 500 4 GLN A 61 69.19 69.67
REMARK 500 4 ASN A 102 43.32 -96.67
REMARK 500 5 ILE A 15 -68.24 68.64
REMARK 500 5 SER A 16 -179.68 57.10
REMARK 500 5 THR A 17 167.96 60.12
REMARK 500 5 GLN A 40 -58.16 -125.47
REMARK 500 5 GLN A 61 60.98 75.08
REMARK 500 5 ASN A 102 37.39 -95.92
REMARK 500 5 VAL A 104 -81.87 -52.01
REMARK 500 6 HIS A 14 94.37 -68.43
REMARK 500 6 THR A 17 -73.60 65.61
REMARK 500 6 GLN A 61 67.51 67.56
REMARK 500 6 ASN A 102 33.23 -97.24
REMARK 500 6 ASN A 107 100.52 -57.64
REMARK 500 6 GLU A 110 162.31 173.38
REMARK 500 7 ILE A 15 164.14 58.82
REMARK 500 7 THR A 17 -78.12 64.09
REMARK 500 7 ASP A 19 -79.86 -178.68
REMARK 500 7 LYS A 41 179.25 -54.35
REMARK 500 7 MET A 46 -33.16 -39.17
REMARK 500 7 GLN A 61 65.17 68.74
REMARK 500 7 ASN A 107 101.86 -58.02
REMARK 500 7 PHE A 116 30.84 -98.54
REMARK 500 8 SER A 16 -169.48 178.62
REMARK 500 8 LYS A 41 179.36 -56.12
REMARK 500 8 GLN A 61 68.17 68.29
REMARK 500 8 VAL A 104 -90.68 -48.12
REMARK 500 9 SER A 16 -78.30 64.98
REMARK 500 9 ASP A 19 -65.53 -125.73
REMARK 500 9 GLN A 40 -68.94 -120.40
REMARK 500 9 LYS A 41 175.59 -50.56
REMARK 500 9 GLN A 61 55.45 73.78
REMARK 500 9 ASN A 102 32.76 -99.42
REMARK 500 10 THR A 17 -169.34 56.72
REMARK 500 10 ASP A 19 28.44 -155.84
REMARK 500 10 LYS A 41 179.87 -58.05
REMARK 500 10 VAL A 49 -70.00 -52.07
REMARK 500 10 GLN A 61 65.84 70.00
REMARK 500 10 ASN A 102 34.92 -96.28
REMARK 500 10 VAL A 104 -99.11 -53.88
REMARK 500 10 GLU A 110 91.88 43.09
REMARK 500 11 SER A 16 -66.41 -165.01
REMARK 500 11 THR A 17 -75.12 -150.81
REMARK 500 11 LYS A 41 179.86 -54.17
REMARK 500 11 GLN A 61 63.74 71.13
REMARK 500 11 VAL A 104 -70.18 -56.14
REMARK 500 12 THR A 17 -67.19 68.89
REMARK 500 12 ASP A 19 28.87 -158.19
REMARK 500 12 GLU A 21 -148.78 -107.11
REMARK 500 12 GLN A 40 -73.08 -114.71
REMARK 500 12 LYS A 41 175.20 -48.59
REMARK 500 12 GLN A 61 65.84 71.08
REMARK 500 12 ASN A 102 31.66 -94.76
REMARK 500 12 GLU A 110 -179.39 -170.87
REMARK 500 13 ILE A 15 163.99 60.30
REMARK 500 13 SER A 16 -71.96 -84.89
REMARK 500 13 THR A 17 -53.62 -161.77
REMARK 500 13 GLU A 21 -171.79 56.49
REMARK 500 13 THR A 27 159.55 -49.12
REMARK 500 13 GLN A 61 64.21 70.45
REMARK 500 13 ASN A 102 30.97 -92.93
REMARK 500 14 SER A 16 93.63 47.62
REMARK 500 14 THR A 17 -164.64 63.92
REMARK 500 14 SER A 18 109.12 -54.69
REMARK 500 14 GLU A 21 171.70 56.73
REMARK 500 14 LYS A 41 179.79 -55.93
REMARK 500 14 GLN A 61 66.24 69.81
REMARK 500 14 ASN A 102 37.43 -92.91
REMARK 500 14 VAL A 104 -84.71 -52.32
REMARK 500 14 GLU A 110 137.25 63.64
REMARK 500 15 THR A 17 -72.26 66.30
REMARK 500 15 GLN A 40 -70.24 -114.75
REMARK 500 15 LYS A 41 175.61 -49.04
REMARK 500 15 GLN A 61 63.09 69.88
REMARK 500 16 SER A 16 66.71 -118.48
REMARK 500 16 ASP A 19 133.78 63.85
REMARK 500 16 LYS A 41 179.63 -53.94
REMARK 500 16 GLN A 61 65.49 70.16
REMARK 500 16 ASN A 102 31.34 -99.25
REMARK 500 16 GLU A 110 82.95 -155.85
REMARK 500 17 SER A 16 -66.94 69.43
REMARK 500 17 THR A 17 -45.38 -159.23
REMARK 500 17 GLU A 21 30.80 -153.19
REMARK 500 17 GLN A 61 62.90 71.53
REMARK 500 17 MET A 98 -70.94 -59.39
REMARK 500 17 LYS A 109 91.98 -61.65
REMARK 500 18 ILE A 15 -162.59 55.23
REMARK 500 18 SER A 16 88.12 75.47
REMARK 500 18 GLU A 21 -59.27 -155.35
REMARK 500 18 THR A 27 156.70 -46.12
REMARK 500 18 GLN A 61 59.37 73.32
REMARK 500 18 GLU A 86 125.41 176.22
REMARK 500
REMARK 500 REMARK: NULL
REMARK 600
REMARK 600 HETEROGEN
REMARK 600
REMARK 600 AUTHOR NOTED THAT THE PIPERIZINYL MOIETY PRODUCED NO NOES,
REMARK 600 SO THE POSITIONS OF ITS ATOMS COULD NOT BE DETERMINED
REMARK 600 EXPERIMENTALLY AND ARE NOT INCLUDED IN THE COORDINATES.
REMARK 610
REMARK 610 MISSING HETEROATOM
REMARK 610 THE FOLLOWING RESIDUES HAVE MISSING ATOMS (M=MODEL NUMBER;
REMARK 610 RES=RESIDUE NAME; C=CHAIN IDENTIFIER; SSEQ=SEQUENCE NUMBER;
REMARK 610 I=INSERTION CODE):
REMARK 610 M RES C SSEQI
REMARK 610 1 IMY A 120
REMARK 610 2 IMY A 120
REMARK 610 3 IMY A 120
REMARK 610 4 IMY A 120
REMARK 610 5 IMY A 120
REMARK 610 6 IMY A 120
REMARK 610 7 IMY A 120
REMARK 610 8 IMY A 120
REMARK 610 9 IMY A 120
REMARK 610 10 IMY A 120
REMARK 610 11 IMY A 120
REMARK 610 12 IMY A 120
REMARK 610 13 IMY A 120
REMARK 610 14 IMY A 120
REMARK 610 15 IMY A 120
REMARK 610 16 IMY A 120
REMARK 610 17 IMY A 120
REMARK 610 18 IMY A 120
REMARK 800
REMARK 800 SITE
REMARK 800 SITE_IDENTIFIER: AC1
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: BINDING SITE FOR RESIDUE IMY A 120
REMARK 900
REMARK 900 RELATED ENTRIES
REMARK 900 RELATED ID: 1YCQ RELATED DB: PDB
REMARK 900 X-RAY STRUCTURE OF MDM2 WITH A P53 PEPTIDE BY KUSSIE ET AL.
REMARK 900 RELATED ID: 1RV1 RELATED DB: PDB
REMARK 900 X-RAY STRUCTURE OF MDM2 WITH AN IMIDAZOLINE INHIBITOR BY
REMARK 900 LUKACS, KAMMLOTT, AND GRAVES
DBREF 1TTV A 13 119 UNP P56273 MDM2_XENLA 13 119
SEQADV 1TTV LEU A 50 UNP P56273 ILE 50 ENGINEERED
SEQADV 1TTV HIS A 92 UNP P56273 PRO 92 ENGINEERED
SEQADV 1TTV ILE A 95 UNP P56273 LEU 95 ENGINEERED
SEQRES 1 A 107 ASN HIS ILE SER THR SER ASP GLN GLU LYS LEU VAL GLN
SEQRES 2 A 107 PRO THR PRO LEU LEU LEU SER LEU LEU LYS SER ALA GLY
SEQRES 3 A 107 ALA GLN LYS GLU THR PHE THR MET LYS GLU VAL LEU TYR
SEQRES 4 A 107 HIS LEU GLY GLN TYR ILE MET ALA LYS GLN LEU TYR ASP
SEQRES 5 A 107 GLU LYS GLN GLN HIS ILE VAL HIS CYS SER ASN ASP PRO
SEQRES 6 A 107 LEU GLY GLU LEU PHE GLY VAL GLN GLU PHE SER VAL LYS
SEQRES 7 A 107 GLU HIS ARG ARG ILE TYR ALA MET ILE SER ARG ASN LEU
SEQRES 8 A 107 VAL SER ALA ASN VAL LYS GLU SER SER GLU ASP ILE PHE
SEQRES 9 A 107 GLY ASN VAL
HET IMY A 120 54
HETNAM IMY 1-{[4,5-BIS(4-CHLOROPHENYL)-2-(2-ISOPROPOXY-4-
HETNAM 2 IMY METHOXYPHENYL)-4,5-DIHYDRO-1H-IMIDAZOL-1-
HETNAM 3 IMY YL]CARBONYL}PIPERAZINE
HETSYN IMY CIS-[4,5-BIS-(4-CHLOROPHENYL)-2-(2-ISOPROPOXY-4-
HETSYN 2 IMY METHOXYPHENYL)-4,5-DIHYD ROIMIDAZOL-1-YL]-PIPERAZIN-1-
HETSYN 3 IMY YL-METHANONE
FORMUL 2 IMY C30 H32 CL2 N4 O3
HELIX 1 1 THR A 27 ALA A 37 1 11
HELIX 2 2 THR A 45 GLN A 61 1 17
HELIX 3 3 ASP A 76 GLY A 83 1 8
HELIX 4 4 GLU A 91 ARG A 101 1 11
SHEET 1 A 2 VAL A 24 PRO A 26 0
SHEET 2 A 2 LEU A 103 ALA A 106 -1 O SER A 105 N GLN A 25
SHEET 1 B 2 ILE A 70 VAL A 71 0
SHEET 2 B 2 PHE A 87 SER A 88 -1 O PHE A 87 N VAL A 71
SITE 1 AC1 8 LEU A 50 LEU A 53 GLY A 54 ILE A 57
SITE 2 AC1 8 GLN A 68 HIS A 69 VAL A 89 HIS A 92
CRYST1 1.000 1.000 1.000 90.00 90.00 90.00 P 1 1
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 1.000000 0.000000 0.000000 0.00000
SCALE2 0.000000 1.000000 0.000000 0.00000
SCALE3 0.000000 0.000000 1.000000 0.00000
MODEL 1
(ATOM LINES ARE NOT SHOWN.)
END
