data_15613 ####################### # Entry information # ####################### save_entry_information _Saveframe_category entry_information _Entry_title ; SOLUTION STRUCTURE OF THE BIS-C2-2-NAPHTHYLPYRROLO[2,1-c][1,4]BENZODIAZEPINE (DA046) DNA ADDUCT: THE MOLECULAR BASIS FOR DNA HELIX STABILIZATION. ; _BMRB_accession_number 15613 _BMRB_flat_file_name bmr15613.str _Entry_type original _Submission_date 2008-01-02 _Accession_date 2008-01-02 _Entry_origination author _NMR_STAR_version 2.1.1 _Experimental_method NMR _Details . loop_ _Author_ordinal _Author_family_name _Author_given_name _Author_middle_initials _Author_family_title 1 Antonow Dyeison . . 2 Barata Teresa . . 3 Jenkins Terence C. . 4 Parkinson Gary N. . 5 Howard Philip W. . 6 Thurston David E. . 7 Zloh Mire . . stop_ loop_ _Saveframe_category_type _Saveframe_category_type_count assigned_chemical_shifts 2 stop_ loop_ _Data_type _Data_type_count "1H chemical shifts" 138 stop_ loop_ _Revision_date _Revision_keyword _Revision_author _Revision_detail 2011-10-12 update BMRB 'update ligand saveframes' 2010-07-16 update BMRB 'update DNA residue label to two-letter code' 2008-06-26 original author 'original release' stop_ save_ ############################# # Citation for this entry # ############################# save_entry_citation1 _Saveframe_category entry_citation _Citation_full . _Citation_title 'Parallel Synthesis of a Novel C2-Aryl Pyrrolo[2,1-c][1,4]benzodiazepine (PBD) Library' _Citation_status published _Citation_type journal _CAS_abstract_code . _MEDLINE_UI_code . _PubMed_ID 17397227 loop_ _Author_ordinal _Author_family_name _Author_given_name _Author_middle_initials _Author_family_title 1 Antonow Dyeison . . 2 Cooper Nectaroula . . 3 Howard Philip W. . 4 Thurston David E. . stop_ _Journal_abbreviation 'J. Comb. Chem.' _Journal_volume 9 _Journal_issue 3 _Journal_CSD . _Book_chapter_title . _Book_volume . _Book_series . _Book_ISBN . _Conference_state_province . _Conference_abstract_number . _Page_first 437 _Page_last 445 _Year 2007 _Details . loop_ _Keyword anticancer Pyrrolo[2,1-c][1,4]benzodiazepine stop_ save_ ################################## # Molecular system description # ################################## save_assembly _Saveframe_category molecular_system _Mol_system_name 5'-D(*(DA)P*(DA)P*(DT)P*(DC)P*(DT)P*(DT)P*(DT)P*(DA)P*(DA)P*(DA)P*(DG)P*(DA)P*(DT)P*(DT))-3' _Enzyme_commission_number . loop_ _Mol_system_component_name _Mol_label 'DNA (5'-D(*(DA)P*(DA)P*(DT)P*(DC)P*(DT)P*(DT)P*(DT)P*(DA)P*(DA)P*(DA)P*(DG)P*(DA)P*(DT)P*(DT))-3')_1' $DNA_AATCTTTAAAGATT 'DNA (5'-D(*(DA)P*(DA)P*(DT)P*(DC)P*(DT)P*(DT)P*(DT)P*(DA)P*(DA)P*(DA)P*(DG)P*(DA)P*(DT)P*(DT))-3')_2' $DNA_AATCTTTAAAGATT PZD_1 $PZD PZD_2 $PZD stop_ _System_molecular_weight . _System_physical_state native _System_oligomer_state ? _System_paramagnetic no _System_thiol_state . _Database_query_date . _Details . save_ ######################## # Monomeric polymers # ######################## save_DNA_AATCTTTAAAGATT _Saveframe_category monomeric_polymer _Mol_type polymer _Mol_polymer_class DNA _Name_common DNA_AATCTTTAAAGATT _Molecular_mass 2338.598 _Mol_thiol_state 'not present' _Details . ############################## # Polymer residue sequence # ############################## _Residue_count 14 _Mol_residue_sequence AATCTTTAAAGATT loop_ _Residue_seq_code _Residue_label 1 DA 2 DA 3 DT 4 DC 5 DT 6 DT 7 DT 8 DA 9 DA 10 DA 11 DG 12 DA 13 DT 14 DT stop_ _Sequence_homology_query_date . _Sequence_homology_query_revised_last_date . save_ ############# # Ligands # ############# save_PZD _Saveframe_category ligand _Mol_type non-polymer _Name_common "PZD ((11aS)-7,8-dimethoxy-2-naphthalen-2-yl-1,10,11,11a-tetrahydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-5-one)" _BMRB_code . _PDB_code PZD _Molecular_mass 386.443 _Mol_charge 0 _Mol_paramagnetic . _Mol_aromatic yes _Details ; Information obtained from PDB's Chemical Component Dictionary at http://wwpdb-remediation.rutgers.edu/downloads.html Downloaded on Wed Oct 12 15:58:28 2011 ; loop_ _Atom_name _PDB_atom_name _Atom_type _Atom_chirality _Atom_charge _Atom_oxidation_number _Atom_unpaired_electrons C1A C1A C . 0 . ? C2A C2A C . 0 . ? C3A C3A C . 0 . ? C4A C4A C . 0 . ? C5A C5A C . 0 . ? C6A C6A C . 0 . ? C7A C7A C . 0 . ? N1A N1A N . 0 . ? C8A C8A C . 0 . ? C10 C10 C . 0 . ? C11 C11 C . 0 . ? C12 C12 C . 0 . ? O1A O1A O . 0 . ? C13 C13 C . 0 . ? C14 C14 C . 0 . ? C15 C15 C . 0 . ? C16 C16 C . 0 . ? C17 C17 C . 0 . ? C18 C18 C . 0 . ? C19 C19 C . 0 . ? C20 C20 C . 0 . ? C21 C21 C . 0 . ? C22 C22 C . 0 . ? O2A O2A O . 0 . ? C23 C23 C . 0 . ? O3A O3A O . 0 . ? C24 C24 C . 0 . ? C9A C9A C . 0 . ? N2A N2A N . 0 . ? H8A H8A H . 0 . ? H24 H24 H . 0 . ? H24A H24A H . 0 . ? H24B H24B H . 0 . ? H23 H23 H . 0 . ? H23A H23A H . 0 . ? H23B H23B H . 0 . ? H3A H3A H . 0 . ? H6A H6A H . 0 . ? H16 H16 H . 0 . ? H22 H22 H . 0 . ? H15 H15 H . 0 . ? H17 H17 H . 0 . ? H18 H18 H . 0 . ? H21 H21 H . 0 . ? H19 H19 H . 0 . ? H10 H10 H . 0 . ? H12 H12 H . 0 . ? H12A H12A H . 0 . ? H9A H9A H . 0 . ? HN2A HN2A H . 0 . ? H9AA H9AA H . 0 . ? stop_ loop_ _Bond_order _Bond_atom_one_atom_name _Bond_atom_two_atom_name _PDB_bond_atom_one_atom_name _PDB_bond_atom_two_atom_name SING O3A C1A ? ? DOUB C6A C1A ? ? SING C1A C2A ? ? SING C2A O2A ? ? DOUB C2A C3A ? ? SING C4A C3A ? ? SING C3A H3A ? ? DOUB C5A C4A ? ? SING C4A C7A ? ? SING C6A C5A ? ? SING N2A C5A ? ? SING H6A C6A ? ? SING N1A C7A ? ? DOUB C7A O1A ? ? SING C8A N1A ? ? SING N1A C10 ? ? SING C9A C8A ? ? SING H8A C8A ? ? SING C12 C8A ? ? DOUB C11 C10 ? ? SING C10 H10 ? ? SING C12 C11 ? ? SING C11 C20 ? ? SING H12A C12 ? ? SING H12 C12 ? ? DOUB C18 C13 ? ? SING C19 C13 ? ? SING C13 C14 ? ? DOUB C14 C15 ? ? SING C14 C22 ? ? SING C16 C15 ? ? SING C15 H15 ? ? DOUB C17 C16 ? ? SING C16 H16 ? ? SING H17 C17 ? ? SING C18 C17 ? ? SING H18 C18 ? ? SING H19 C19 ? ? DOUB C19 C20 ? ? SING C20 C21 ? ? DOUB C21 C22 ? ? SING C21 H21 ? ? SING C22 H22 ? ? SING O2A C23 ? ? SING H23B C23 ? ? SING C23 H23 ? ? SING C23 H23A ? ? SING C24 O3A ? ? SING H24A C24 ? ? SING C24 H24 ? ? SING C24 H24B ? ? SING H9A C9A ? ? SING C9A N2A ? ? SING C9A H9AA ? ? SING HN2A N2A ? ? stop_ _Mol_thiol_state . _Sequence_homology_query_date . save_ #################### # Natural source # #################### save_natural_source _Saveframe_category natural_source loop_ _Mol_label _Organism_name_common _NCBI_taxonomy_ID _Superkingdom _Kingdom _Genus _Species $DNA_AATCTTTAAAGATT . . . . . . stop_ save_ ######################### # Experimental source # ######################### save_experimental_source _Saveframe_category experimental_source loop_ _Mol_label _Production_method _Host_organism_name_common _Genus _Species _Strain _Vector_name _Details $DNA_AATCTTTAAAGATT 'chemical synthesis' . . . . . ; The 14-mer nucleotide sequence AATCTTTAAAGATT was synthesised using a Applied Biosystems 391 DNA synthesizer using solid-phase -cyanoethylphosphoramidite synthetic protocol. The 5 -dimethoxytritylated oligonucleotide was removed from the synthesis column and treated with concentrated ammonium (10 ml) at 60 C for over 16 h. The DNA sequence was purified by solid-phase HPLC (BioCad Sprint, flux 4 mL/min using a R3 Column, 10 x 100 mm) at room temperature, and the column had been previously equilibrated with buffer A (3 column volumes (CV), 100 mM ammonium acetate; pH 10.0). For the double helix formation, the self-complementary DNA strands were re-suspended in 90% H2O:10% 2H2O buffer solution (500 L, [sodium phosphate 10 mM:sodium chloride 100 mM], pH 6.85) and heated at 65 C for 5 min in a water bath. The solution was allowed to slowly (16 h) cool down to 25 C. This procedure was repeated to insure proper annealing. ; $PZD 'chemical synthesis' . . . . . 'See: Antonow, D., Cooper, N., Howard, P. W. & Thurston, D. E. (2007). Parallel Synthesis of a Novel C2-Aryl Pyrrolo[2,1-c][1,4]benzodiazepine (PBD) Library. Journal of Combinatorial Chemistry 9, 437-445.' stop_ save_ ##################################### # Sample contents and methodology # ##################################### ######################## # Sample description # ######################## save_sample_1 _Saveframe_category sample _Sample_type solution _Details 'The 0.68 mM DNA solution was incubated with PZD(7.5 mg as a slurry) at room temperature for 48 h under gentle shaking. The excess PZD was removed by filtration (Millipore 25 mm syringe filters, 0.45 m pore size) and the filtrated was collected in the NMR tube. This purification method was verified by repeating the procedure with PZD in D2O ,where filtrate showed no peaks even with higher number of scans (1048).' loop_ _Mol_label _Concentration_value _Concentration_value_units _Isotopic_labeling $DNA_AATCTTTAAAGATT 0.68 mM 'natural abundance' $PZD 0.68 mM . 'sodium phosphate' 10 mM . 'sodium chloride' 100 mM . D2O 10 % '[U-100% 2H]' H2O 90 % . stop_ save_ ############################ # Computer software used # ############################ save_X-PLOR_NIH _Saveframe_category software _Name X-PLOR_NIH _Version 2.16 loop_ _Vendor _Address _Electronic_address 'Schwieters, Kuszewski, Tjandra and Clore' . . stop_ loop_ _Task refinement stop_ _Details . save_ save_TOPSPIN _Saveframe_category software _Name TOPSPIN _Version 1.3 loop_ _Vendor _Address _Electronic_address 'Bruker Biospin' . . stop_ loop_ _Task collection processing stop_ _Details . save_ save_AMIX _Saveframe_category software _Name AMIX _Version 3.5.5 loop_ _Vendor _Address _Electronic_address 'Bruker Biospin' . . stop_ loop_ _Task 'peak picking' 'chemical shift assignment' stop_ _Details . save_ ######################### # Experimental detail # ######################### ################################## # NMR Spectrometer definitions # ################################## save_spectrometer_1 _Saveframe_category NMR_spectrometer _Manufacturer Bruker _Model Avance _Field_strength 500 _Details . save_ ############################# # NMR applied experiments # ############################# save_2D_1H-1H_TOCSY_1 _Saveframe_category NMR_applied_experiment _Experiment_name '2D 1H-1H TOCSY' _Sample_label $sample_1 save_ save_2D_1H-1H_COSY_2 _Saveframe_category NMR_applied_experiment _Experiment_name '2D 1H-1H COSY' _Sample_label $sample_1 save_ save_2D_1H-1H_NOESY_3 _Saveframe_category NMR_applied_experiment _Experiment_name '2D 1H-1H NOESY' _Sample_label $sample_1 save_ ####################### # Sample conditions # ####################### save_sample_conditions_1 _Saveframe_category sample_conditions _Details . loop_ _Variable_type _Variable_value _Variable_value_error _Variable_value_units temperature 298 . K pH 6.85 . pH pressure 1 . atm 'ionic strength' 130 . mM stop_ save_ #################### # NMR parameters # #################### ############################## # Assigned chemical shifts # ############################## ################################ # Chemical shift referencing # ################################ save_chemical_shift_reference_1 _Saveframe_category chemical_shift_reference _Details . loop_ _Mol_common_name _Atom_type _Atom_isotope_number _Atom_group _Chem_shift_units _Chem_shift_value _Reference_method _Reference_type _External_reference_sample_geometry _External_reference_location _External_reference_axis _Indirect_shift_ratio TSP H 1 'methyl protons' ppm 0.00 internal direct . . . 1.000000000 stop_ save_ ################################### # Assigned chemical shift lists # ################################### ################################################################### # Chemical Shift Ambiguity Index Value Definitions # # # # The values other than 1 are used for those atoms with different # # chemical shifts that cannot be assigned to stereospecific atoms # # or to specific residues or chains. # # # # Index Value Definition # # # # 1 Unique (including isolated methyl protons, # # geminal atoms, and geminal methyl # # groups with identical chemical shifts) # # (e.g. ILE HD11, HD12, HD13 protons) # # 2 Ambiguity of geminal atoms or geminal methyl # # proton groups (e.g. ASP HB2 and HB3 # # protons, LEU CD1 and CD2 carbons, or # # LEU HD11, HD12, HD13 and HD21, HD22, # # HD23 methyl protons) # # 3 Aromatic atoms on opposite sides of # # symmetrical rings (e.g. TYR HE1 and HE2 # # protons) # # 4 Intraresidue ambiguities (e.g. LYS HG and # # HD protons or TRP HZ2 and HZ3 protons) # # 5 Interresidue ambiguities (LYS 12 vs. LYS 27) # # 6 Intermolecular ambiguities (e.g. ASP 31 CA # # in monomer 1 and ASP 31 CA in monomer 2 # # of an asymmetrical homodimer, duplex # # DNA assignments, or other assignments # # that may apply to atoms in one or more # # molecule in the molecular assembly) # # 9 Ambiguous, specific ambiguity not defined # # # ################################################################### save_assigned_chem_shift_list_1_1 _Saveframe_category assigned_chemical_shifts _Details . loop_ _Software_label $AMIX stop_ loop_ _Experiment_label '2D 1H-1H TOCSY' '2D 1H-1H NOESY' stop_ loop_ _Sample_label $sample_1 stop_ _Sample_conditions_label $sample_conditions_1 _Chem_shift_reference_set_label $chemical_shift_reference_1 _Mol_system_component_name 'DNA (5'-D(*(DA)P*(DA)P*(DT)P*(DC)P*(DT)P*(DT)P*(DT)P*(DA)P*(DA)P*(DA)P*(DG)P*(DA)P*(DT)P*(DT))-3')_1' _Text_data_format . _Text_data . loop_ _Atom_shift_assign_ID _Residue_author_seq_code _Residue_seq_code _Residue_label _Atom_name _Atom_type _Chem_shift_value _Chem_shift_value_error _Chem_shift_ambiguity_code 1 1 1 DA H1' H 5.88 . . 2 1 1 DA H2 H 7.5 . . 3 1 1 DA H2' H 2.5 . . 4 1 1 DA H2'' H 2.71 . . 5 1 1 DA H3' H 4.79 . . 6 1 1 DA H4' H 4.11 . . 7 1 1 DA H8 H 8.03 . . 8 2 2 DA H1' H 6.21 . . 9 2 2 DA H2 H 7.48 . . 10 2 2 DA H2' H 2.6 . . 11 2 2 DA H2'' H 2.91 . . 12 2 2 DA H3' H 4.8 . . 13 2 2 DA H4' H 4.41 . . 14 2 2 DA H8 H 8.18 . . 15 3 3 DT H3 H 13.59 . . 16 3 3 DT H1' H 5.82 . . 17 3 3 DT H2' H 1.97 . . 18 3 3 DT H2'' H 2.41 . . 19 3 3 DT H3' H 4.75 . . 20 3 3 DT H4' H 4.15 . . 21 3 3 DT H6 H 7.03 . . 22 3 3 DT H71 H 1.3 . . 23 3 3 DT H72 H 1.3 . . 24 3 3 DT H73 H 1.3 . . 25 4 4 DC H1' H 6.27 . . 26 4 4 DC H2' H 1.93 . . 27 4 4 DC H2'' H 2.43 . . 28 4 4 DC H3' H 4.8 . . 29 4 4 DC H4' H 3.98 . . 30 4 4 DC H5 H 5.32 . . 31 4 4 DC H6 H 7.4 . . 32 4 4 DC H41 H 6.42 . . 33 5 5 DT H3 H 14 . . 34 5 5 DT H1' H 5.51 . . 35 5 5 DT H2' H 1.9 . . 36 5 5 DT H2'' H 1.93 . . 37 5 5 DT H3' H 4.82 . . 38 5 5 DT H4' H 4.18 . . 39 5 5 DT H5' H 3.67 . . 40 5 5 DT H6 H 7.18 . . 41 5 5 DT H71 H 1.51 . . 42 5 5 DT H72 H 1.51 . . 43 5 5 DT H73 H 1.51 . . 44 6 6 DT H3 H 13.47 . . 45 6 6 DT H1' H 5.71 . . 46 6 6 DT H2' H 1.87 . . 47 6 6 DT H2'' H 2.13 . . 48 6 6 DT H3' H 4.6 . . 49 6 6 DT H4' H 4.16 . . 50 6 6 DT H5' H 3.16 . . 51 6 6 DT H6 H 7.17 . . 52 6 6 DT H71 H 1.52 . . 53 6 6 DT H72 H 1.52 . . 54 6 6 DT H73 H 1.52 . . 55 7 7 DT H3 H 13.16 . . 56 7 7 DT H1' H 5.81 . . 57 7 7 DT H2' H 2.3 . . 58 7 7 DT H2'' H 2.46 . . 59 7 7 DT H3' H 4.81 . . 60 7 7 DT H4' H 4.07 . . 61 7 7 DT H5' H 3.15 . . 62 7 7 DT H6 H 7.24 . . 63 7 7 DT H71 H 1.48 . . 64 7 7 DT H72 H 1.48 . . 65 7 7 DT H73 H 1.48 . . 66 8 8 DA H1' H 5.6 . . 67 8 8 DA H2 H 6.9 . . 68 8 8 DA H2' H 2.65 . . 69 8 8 DA H2'' H 2.69 . . 70 8 8 DA H3' H 4.93 . . 71 8 8 DA H4' H 4.12 . . 72 8 8 DA H8 H 8.05 . . 73 9 9 DA H1' H 5.48 . . 74 9 9 DA H2 H 7.26 . . 75 9 9 DA H2' H 2.44 . . 76 9 9 DA H2'' H 2.69 . . 77 9 9 DA H3' H 4.91 . . 78 9 9 DA H4' H 4.12 . . 79 9 9 DA H8 H 7.95 . . 80 10 10 DA H1' H 5.82 . . 81 10 10 DA H2 H 7.84 . . 82 10 10 DA H2' H 2.27 . . 83 10 10 DA H2'' H 2.46 . . 84 10 10 DA H3' H 4.83 . . 85 10 10 DA H4' H 4.16 . . 86 10 10 DA H8 H 7.83 . . 87 10 10 DA H61 H 6.01 . . 88 11 11 DG H1 H 12.8 . . 89 11 11 DG H1' H 5.83 . . 90 11 11 DG H2' H 2.6 . . 91 11 11 DG H2'' H 2.74 . . 92 11 11 DG H3' H 4.96 . . 93 11 11 DG H4' H 4.13 . . 94 11 11 DG H8 H 8.2 . . 95 11 11 DG H21 H 8.32 . . 96 12 12 DA H1' H 6.19 . . 97 12 12 DA H2 H 7.96 . . 98 12 12 DA H2' H 2.39 . . 99 12 12 DA H2'' H 2.62 . . 100 12 12 DA H3' H 4.89 . . 101 12 12 DA H4' H 4.16 . . 102 12 12 DA H8 H 7.93 . . 103 13 13 DT H1' H 6.06 . . 104 13 13 DT H2' H 1.98 . . 105 13 13 DT H2'' H 2.4 . . 106 13 13 DT H3' H 4.67 . . 107 13 13 DT H4' H 4 . . 108 13 13 DT H6 H 7.07 . . 109 13 13 DT H71 H 1.11 . . 110 13 13 DT H72 H 1.11 . . 111 13 13 DT H73 H 1.11 . . 112 14 14 DT H1' H 6.24 . . 113 14 14 DT H2' H 2.19 . . 114 14 14 DT H2'' H 2.18 . . 115 14 14 DT H3' H 4.52 . . 116 14 14 DT H4' H 4.04 . . 117 14 14 DT H5' H 3.19 . . 118 14 14 DT H6 H 7.3 . . 119 14 14 DT H71 H 1.49 . . 120 14 14 DT H72 H 1.49 . . 121 14 14 DT H73 H 1.49 . . stop_ save_ save_assigned_chem_shift_list_1_2 _Saveframe_category assigned_chemical_shifts _Details . loop_ _Software_label $AMIX stop_ loop_ _Experiment_label '2D 1H-1H TOCSY' '2D 1H-1H NOESY' stop_ loop_ _Sample_label $sample_1 stop_ _Sample_conditions_label $sample_conditions_1 _Chem_shift_reference_set_label $chemical_shift_reference_1 _Mol_system_component_name 'DNA (5'-D(*(DA)P*(DA)P*(DT)P*(DC)P*(DT)P*(DT)P*(DT)P*(DA)P*(DA)P*(DA)P*(DG)P*(DA)P*(DT)P*(DT))-3')_2' _Text_data_format . _Text_data . loop_ _Atom_shift_assign_ID _Residue_author_seq_code _Residue_seq_code _Residue_label _Atom_name _Atom_type _Chem_shift_value _Chem_shift_value_error _Chem_shift_ambiguity_code 1 . 1 PZD H1A H 4.13 . . 2 . 1 PZD H4A H 3.98 . . 3 . 1 PZD H5A H 3.84 . . 4 . 1 PZD H8A H 7.17 . . 5 . 1 PZD H9A H 6.6 . . 6 . 1 PZD H10A H 7.45 . . 7 . 1 PZD H11A H 7.47 . . 8 . 1 PZD H12A H 7.79 . . 9 . 1 PZD H13A H 7.8 . . 10 . 1 PZD H14A H 7.85 . . 11 . 1 PZD H15A H 8.2 . . 12 . 1 PZD H16A H 7.6 . . 13 . 1 PZD H17A H 8.05 . . 14 . 1 PZD H18A H 3.99 . . 15 . 1 PZD H19A H 4.03 . . 16 . 1 PZD H20A H 5.84 . . 17 . 1 PZD H21A H 8.3 . . stop_ save_