HEADER APOPTOSIS 29-NOV-06 2O22
TITLE SOLUTION STRUCTURE OF THE ANTI-APOPTOTIC PROTEIN BCL-2 IN COMPLEX WITH
TITLE 2 AN ACYL-SULFONAMIDE-BASED LIGAND
COMPND MOL_ID: 1;
COMPND 2 MOLECULE: APOPTOSIS REGULATOR BCL-2;
COMPND 3 CHAIN: A;
COMPND 4 ENGINEERED: YES
SOURCE MOL_ID: 1;
SOURCE 2 ORGANISM_SCIENTIFIC: HOMO SAPIENS;
SOURCE 3 ORGANISM_COMMON: HUMAN;
SOURCE 4 ORGANISM_TAXID: 9606;
SOURCE 5 GENE: BCL2;
SOURCE 6 EXPRESSION_SYSTEM: ESCHERICHIA COLI BL21(DE3);
SOURCE 7 EXPRESSION_SYSTEM_TAXID: 469008;
SOURCE 8 EXPRESSION_SYSTEM_STRAIN: BL21(DE3);
SOURCE 9 EXPRESSION_SYSTEM_VECTOR_TYPE: PLASMID;
SOURCE 10 EXPRESSION_SYSTEM_PLASMID: PET28B
KEYWDS APOPTOSIS, COMPLEX, BCL
EXPDTA SOLUTION NMR
AUTHOR M.BRUNCKO,T.K.OOST,B.A.BELLI,H.DING,M.K.JOSEPH,A.KUNZER,D.MARTINEAU,
AUTHOR 2 W.J.MCCLELLAN,M.MITTEN,S.C.NG,P.M.NIMMER,T.OLTERSDORF,C.M.PARK,
AUTHOR 3 A.M.PETROS,A.R.SHOEMAKER,X.SONG,X.WANG,M.D.WENDT,H.ZHANG,S.W.FESIK,
AUTHOR 4 S.H.ROSENBERG,S.W.ELMORE
REVDAT 3 22-DEC-10 2O22 1 REMARK
REVDAT 2 24-FEB-09 2O22 1 VERSN
REVDAT 1 27-FEB-07 2O22 0
JRNL AUTH M.BRUNCKO,T.K.OOST,B.A.BELLI,H.DING,M.K.JOSEPH,A.KUNZER,
JRNL AUTH 2 D.MARTINEAU,W.J.MCCLELLAN,M.MITTEN,S.C.NG,P.M.NIMMER,
JRNL AUTH 3 T.OLTERSDORF,C.M.PARK,A.M.PETROS,A.R.SHOEMAKER,X.SONG,
JRNL AUTH 4 X.WANG,M.D.WENDT,H.ZHANG,S.W.FESIK,S.H.ROSENBERG,S.W.ELMORE
JRNL TITL STUDIES LEADING TO POTENT, DUAL INHIBITORS OF BCL-2 AND
JRNL TITL 2 BCL-XL.
JRNL REF J.MED.CHEM. V. 50 641 2007
JRNL REFN ISSN 0022-2623
JRNL PMID 17256834
JRNL DOI 10.1021/JM061152T
REMARK 2
REMARK 2 RESOLUTION. NOT APPLICABLE.
REMARK 3
REMARK 3 REFINEMENT.
REMARK 3 PROGRAM : CNS
REMARK 3 AUTHORS : BRUNGER A. T. ETALL
REMARK 3
REMARK 3 OTHER REFINEMENT REMARKS: NULL
REMARK 4
REMARK 4 2O22 COMPLIES WITH FORMAT V. 3.15, 01-DEC-08
REMARK 100
REMARK 100 THIS ENTRY HAS BEEN PROCESSED BY RCSB ON 07-DEC-06.
REMARK 100 THE RCSB ID CODE IS RCSB040588.
REMARK 210
REMARK 210 EXPERIMENTAL DETAILS
REMARK 210 EXPERIMENT TYPE : NMR
REMARK 210 TEMPERATURE (KELVIN) : 298
REMARK 210 PH : 8.0
REMARK 210 IONIC STRENGTH : 25 MM TRIS; 150 MM SODIUM
REMARK 210 CHLORIDE
REMARK 210 PRESSURE : 1 ATM
REMARK 210 SAMPLE CONTENTS : 25 MM TRIS BUFFER; 150 MM SODIUM
REMARK 210 CHLORIDE; 90% H2O, 10% D2O
REMARK 210
REMARK 210 NMR EXPERIMENTS CONDUCTED : 3D_13C-SEPARATED_NOESY
REMARK 210 SPECTROMETER FIELD STRENGTH : 600 MHZ; 800 MHZ
REMARK 210 SPECTROMETER MODEL : DRX
REMARK 210 SPECTROMETER MANUFACTURER : BRUKER
REMARK 210
REMARK 210 STRUCTURE DETERMINATION.
REMARK 210 SOFTWARE USED : NULL
REMARK 210 METHOD USED : SIMULATED ANNEALING
REMARK 210
REMARK 210 CONFORMERS, NUMBER CALCULATED : NULL
REMARK 210 CONFORMERS, NUMBER SUBMITTED : 1
REMARK 210 CONFORMERS, SELECTION CRITERIA : NULL
REMARK 210
REMARK 210 BEST REPRESENTATIVE CONFORMER IN THIS ENSEMBLE : 1
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 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 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 500
REMARK 500 GEOMETRY AND STEREOCHEMISTRY
REMARK 500 SUBTOPIC: CLOSE CONTACTS
REMARK 500
REMARK 500 THE FOLLOWING ATOMS ARE IN CLOSE CONTACT.
REMARK 500
REMARK 500 ATM1 RES C SSEQI ATM2 RES C SSEQI DISTANCE
REMARK 500 HA3 GLY A 142 HN17 LIU A 1000 1.57
REMARK 500
REMARK 500 REMARK: NULL
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 ALA A 2 73.08 178.15
REMARK 500 ARG A 4 31.28 -144.90
REMARK 500 GLU A 27 91.64 -54.94
REMARK 500 GLU A 36 83.95 47.48
REMARK 500 ARG A 38 57.77 -107.98
REMARK 500 THR A 39 -78.50 -50.38
REMARK 500 ALA A 41 150.90 68.51
REMARK 500 GLU A 46 -72.62 -53.54
REMARK 500 ASP A 108 -70.76 -174.72
REMARK 500 HIS A 117 172.01 60.14
REMARK 500 THR A 119 134.85 177.71
REMARK 500 ASP A 137 -61.58 -106.66
REMARK 500 ARG A 161 -74.73 -87.96
REMARK 500 GLU A 162 61.61 -178.48
REMARK 500 MET A 163 44.92 -150.06
REMARK 500 HIS A 181 -55.08 -127.97
REMARK 500 ASN A 189 52.47 -111.10
REMARK 500 TYR A 199 53.88 -107.07
REMARK 500 PRO A 201 158.75 -44.22
REMARK 500 SER A 202 98.81 -47.14
REMARK 500 MET A 203 -78.20 83.27
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 LIU A 1000
REMARK 900
REMARK 900 RELATED ENTRIES
REMARK 900 RELATED ID: 2O1Y RELATED DB: PDB
REMARK 900 RELATED ID: 2O21 RELATED DB: PDB
DBREF 2O22 A 1 32 UNP P10415 BCL2_HUMAN 3 34
DBREF 2O22 A 33 48 UNP Q07817 BCLX_HUMAN 29 44
DBREF 2O22 A 89 204 UNP P10415 BCL2_HUMAN 92 207
SEQRES 1 A 164 HIS ALA GLY ARG THR GLY TYR ASP ASN ARG GLU ILE VAL
SEQRES 2 A 164 MET LYS TYR ILE HIS TYR LYS LEU SER GLN ARG GLY TYR
SEQRES 3 A 164 GLU TRP ASP ALA GLY ASP ASP VAL GLU GLU ASN ARG THR
SEQRES 4 A 164 GLU ALA PRO GLU GLY THR GLU SER GLU VAL VAL HIS LEU
SEQRES 5 A 164 THR LEU ARG GLN ALA GLY ASP ASP PHE SER ARG ARG TYR
SEQRES 6 A 164 ARG ARG ASP PHE ALA GLU MET SER SER GLN LEU HIS LEU
SEQRES 7 A 164 THR PRO PHE THR ALA ARG GLY ARG PHE ALA THR VAL VAL
SEQRES 8 A 164 GLU GLU LEU PHE ARG ASP GLY VAL ASN TRP GLY ARG ILE
SEQRES 9 A 164 VAL ALA PHE PHE GLU PHE GLY GLY VAL MET CYS VAL GLU
SEQRES 10 A 164 SER VAL ASN ARG GLU MET SER PRO LEU VAL ASP ASN ILE
SEQRES 11 A 164 ALA LEU TRP MET THR GLU TYR LEU ASN ARG HIS LEU HIS
SEQRES 12 A 164 THR TRP ILE GLN ASP ASN GLY GLY TRP ASP ALA PHE VAL
SEQRES 13 A 164 GLU LEU TYR GLY PRO SER MET ARG
HET LIU A1000 77
HETNAM LIU N-[(4-{[1,1-DIMETHYL-2-(PHENYLTHIO)ETHYL]AMINO}-3-
HETNAM 2 LIU NITROPHENYL)SULFONYL]-4-(4,4-DIMETHYLPIPERIDIN-1-YL)
HETNAM 3 LIU BENZAMIDE
FORMUL 2 LIU C30 H36 N4 O5 S2
HELIX 1 1 ASP A 8 GLN A 23 1 16
HELIX 2 2 GLY A 44 TYR A 105 1 22
HELIX 3 3 ASP A 108 HIS A 117 1 10
HELIX 4 4 THR A 119 PHE A 135 1 17
HELIX 5 5 ASN A 140 GLU A 162 1 23
HELIX 6 6 PRO A 165 ASN A 189 1 25
HELIX 7 7 GLY A 191 TYR A 199 1 9
SITE 1 AC1 10 ALA A 97 PHE A 101 TYR A 105 ASP A 108
SITE 2 AC1 10 TRP A 141 GLY A 142 VAL A 145 ALA A 146
SITE 3 AC1 10 PHE A 195 TYR A 199
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
(ATOM LINES ARE NOT SHOWN.)
END
