data_27287 ####################### # Entry information # ####################### save_entry_information _Saveframe_category entry_information _Entry_title ; Catalytic Domain of Human Aprataxin ; _BMRB_accession_number 27287 _BMRB_flat_file_name bmr27287.str _Entry_type original _Submission_date 2017-10-18 _Accession_date 2017-10-18 _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 Mueller Geoffrey . . 2 Tumbale Percy . . 3 Schellenberg Matthew . . 4 Williams Scott . . 5 London Robert . . stop_ loop_ _Saveframe_category_type _Saveframe_category_type_count assigned_chemical_shifts 1 stop_ loop_ _Data_type _Data_type_count "1H chemical shifts" 149 "13C chemical shifts" 312 "15N chemical shifts" 149 stop_ loop_ _Revision_date _Revision_keyword _Revision_author _Revision_detail 2018-07-17 original BMRB . stop_ _Original_release_date 2017-10-18 save_ ############################# # Citation for this entry # ############################# save_entry_citation _Saveframe_category entry_citation _Citation_full . _Citation_title ; Mechanism of APTX nicked DNA sensing and pleiotropic inactivation in neurodegenerative disease ; _Citation_status published _Citation_type journal _CAS_abstract_code . _MEDLINE_UI_code . _PubMed_ID 29934293 loop_ _Author_ordinal _Author_family_name _Author_given_name _Author_middle_initials _Author_family_title 1 Tumbale Percy . . 2 Schellenberg Matthew J. . 3 Mueller Geoffrey A. . 4 Fairweather Emma . . 5 Watson Mandy . . 6 Little Jessica N. . 7 Krahn Juno . . 8 Waddell Ian . . 9 London Robert E. . 10 Williams 'R Scott' S. . stop_ _Journal_abbreviation 'EMBO J.' _Journal_name_full 'The EMBO journal' _Journal_volume 37 _Journal_issue 14 _Journal_ISSN 1460-2075 _Journal_CSD . _Book_chapter_title . _Book_volume . _Book_series . _Book_ISBN . _Conference_state_province . _Conference_abstract_number . _Page_first e98875 _Page_last e98875 _Year 2018 _Details . save_ ################################## # Molecular system description # ################################## save_assembly _Saveframe_category molecular_system _Mol_system_name APTX _Enzyme_commission_number . loop_ _Mol_system_component_name _Mol_label APTX $hAPTX 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_hAPTX _Saveframe_category monomeric_polymer _Mol_type polymer _Mol_polymer_class protein _Name_common hAPTX _Molecular_mass . _Mol_thiol_state unknown _Details . ############################## # Polymer residue sequence # ############################## _Residue_count 192 _Mol_residue_sequence ; GSHMKDAPIKKESLGHWSQG LKISMQDPKMQVYKDEQVVV IKDKYPKARYHWLVLPWTSI SSLKAVAREHLELLKHMHTV GEKVIVDFAGSSKLRFRLGY HAIPSMSHVHLHVISQDFDS PCLKNKKHWNSFNTEYFLES QAVIEMVQEAGRVTVRDGMP ELLKLPLRCHECQQLLPSIP QLKEHLRKHWTQ ; loop_ _Residue_seq_code _Residue_author_seq_code _Residue_label 1 151 GLY 2 152 SER 3 153 HIS 4 154 MET 5 155 LYS 6 156 ASP 7 157 ALA 8 158 PRO 9 159 ILE 10 160 LYS 11 161 LYS 12 162 GLU 13 163 SER 14 164 LEU 15 165 GLY 16 166 HIS 17 167 TRP 18 168 SER 19 169 GLN 20 170 GLY 21 171 LEU 22 172 LYS 23 173 ILE 24 174 SER 25 175 MET 26 176 GLN 27 177 ASP 28 178 PRO 29 179 LYS 30 180 MET 31 181 GLN 32 182 VAL 33 183 TYR 34 184 LYS 35 185 ASP 36 186 GLU 37 187 GLN 38 188 VAL 39 189 VAL 40 190 VAL 41 191 ILE 42 192 LYS 43 193 ASP 44 194 LYS 45 195 TYR 46 196 PRO 47 197 LYS 48 198 ALA 49 199 ARG 50 200 TYR 51 201 HIS 52 202 TRP 53 203 LEU 54 204 VAL 55 205 LEU 56 206 PRO 57 207 TRP 58 208 THR 59 209 SER 60 210 ILE 61 211 SER 62 212 SER 63 213 LEU 64 214 LYS 65 215 ALA 66 216 VAL 67 217 ALA 68 218 ARG 69 219 GLU 70 220 HIS 71 221 LEU 72 222 GLU 73 223 LEU 74 224 LEU 75 225 LYS 76 226 HIS 77 227 MET 78 228 HIS 79 229 THR 80 230 VAL 81 231 GLY 82 232 GLU 83 233 LYS 84 234 VAL 85 235 ILE 86 236 VAL 87 237 ASP 88 238 PHE 89 239 ALA 90 240 GLY 91 241 SER 92 242 SER 93 243 LYS 94 244 LEU 95 245 ARG 96 246 PHE 97 247 ARG 98 248 LEU 99 249 GLY 100 250 TYR 101 251 HIS 102 252 ALA 103 253 ILE 104 254 PRO 105 255 SER 106 256 MET 107 257 SER 108 258 HIS 109 259 VAL 110 260 HIS 111 261 LEU 112 262 HIS 113 263 VAL 114 264 ILE 115 265 SER 116 266 GLN 117 267 ASP 118 268 PHE 119 269 ASP 120 270 SER 121 271 PRO 122 272 CYS 123 273 LEU 124 274 LYS 125 275 ASN 126 276 LYS 127 277 LYS 128 278 HIS 129 279 TRP 130 280 ASN 131 281 SER 132 282 PHE 133 283 ASN 134 284 THR 135 285 GLU 136 286 TYR 137 287 PHE 138 288 LEU 139 289 GLU 140 290 SER 141 291 GLN 142 292 ALA 143 293 VAL 144 294 ILE 145 295 GLU 146 296 MET 147 297 VAL 148 298 GLN 149 299 GLU 150 300 ALA 151 301 GLY 152 302 ARG 153 303 VAL 154 304 THR 155 305 VAL 156 306 ARG 157 307 ASP 158 308 GLY 159 309 MET 160 310 PRO 161 311 GLU 162 312 LEU 163 313 LEU 164 314 LYS 165 315 LEU 166 316 PRO 167 317 LEU 168 318 ARG 169 319 CYS 170 320 HIS 171 321 GLU 172 322 CYS 173 323 GLN 174 324 GLN 175 325 LEU 176 326 LEU 177 327 PRO 178 328 SER 179 329 ILE 180 330 PRO 181 331 GLN 182 332 LEU 183 333 LYS 184 334 GLU 185 335 HIS 186 336 LEU 187 337 ARG 188 338 LYS 189 339 HIS 190 340 TRP 191 341 THR 192 342 GLN stop_ _Sequence_homology_query_date . _Sequence_homology_query_revised_last_date . save_ #################### # Natural source # #################### save_natural_source _Saveframe_category natural_source loop_ _Mol_label _Organism_name_common _NCBI_taxonomy_ID _Superkingdom _Kingdom _Genus _Species $hAPTX Human 9606 Eukaryota Metazoa Homo sapiens 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 $hAPTX 'recombinant technology' . Escherichia coli . pET stop_ save_ ##################################### # Sample contents and methodology # ##################################### ######################## # Sample description # ######################## save_sample_1 _Saveframe_category sample _Sample_type solution _Details . loop_ _Mol_label _Concentration_value _Concentration_value_units _Isotopic_labeling $hAPTX 1 mM '[U-100% 13C; U-100% 15N]' 'Na phosphate NaH2PO4' 5 mM 'natural abundance' KCl 1.3 mM 'natural abundance' NaCl 67 mM 'natural abundance' 'K phosphate KH2PO4' 0.8 mM 'natural abundance' stop_ save_ ############################ # Computer software used # ############################ save_NMRPipe _Saveframe_category software _Name NMRPipe _Version . loop_ _Vendor _Address _Electronic_address 'Delaglio, Grzesiek, Vuister, Zhu, Pfeifer and Bax' . . stop_ loop_ _Task 'data analysis' stop_ _Details . save_ save_NMRView _Saveframe_category software _Name NMRView _Version . loop_ _Vendor _Address _Electronic_address 'Johnson, One Moon Scientific' . . stop_ loop_ _Task 'data analysis' stop_ _Details . save_ ######################### # Experimental detail # ######################### ################################## # NMR Spectrometer definitions # ################################## save_spectrometer_1 _Saveframe_category NMR_spectrometer _Manufacturer Varian _Model INOVA _Field_strength 600 _Details . save_ ############################# # NMR applied experiments # ############################# save_2D_1H-15N_HSQC_1 _Saveframe_category NMR_applied_experiment _Experiment_name '2D 1H-15N HSQC' _Sample_label $sample_1 save_ save_3D_HNCA_2 _Saveframe_category NMR_applied_experiment _Experiment_name '3D HNCA' _Sample_label $sample_1 save_ save_3D_HNCACB_3 _Saveframe_category NMR_applied_experiment _Experiment_name '3D HNCACB' _Sample_label $sample_1 save_ save_3D_HN(CO)CA_4 _Saveframe_category NMR_applied_experiment _Experiment_name '3D HN(CO)CA' _Sample_label $sample_1 save_ save_3D_CBCA(CO)NH_5 _Saveframe_category NMR_applied_experiment _Experiment_name '3D CBCA(CO)NH' _Sample_label $sample_1 save_ save_3D_HCCH-TOCSY_6 _Saveframe_category NMR_applied_experiment _Experiment_name '3D HCCH-TOCSY' _Sample_label $sample_1 save_ save_3D_C(CO)NH_7 _Saveframe_category NMR_applied_experiment _Experiment_name '3D C(CO)NH' _Sample_label $sample_1 save_ ####################### # Sample conditions # ####################### save_sample_conditions_1 _Saveframe_category sample_conditions _Details '1/2 strength PBS' loop_ _Variable_type _Variable_value _Variable_value_error _Variable_value_units 'ionic strength' 0.075 . M pH 7.4 . pH pressure 1 . atm temperature 273 . K 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 DSS C 13 'methyl protons' ppm 0 internal indirect . . . 0.251449530 DSS H 1 'methyl protons' ppm 0 internal direct . . . 1 DSS N 15 'methyl protons' ppm 0 internal indirect . . . 0.101329118 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 _Saveframe_category assigned_chemical_shifts _Details . loop_ _Experiment_label '2D 1H-15N HSQC' '3D HNCA' '3D HNCACB' '3D HN(CO)CA' '3D CBCA(CO)NH' '3D HCCH-TOCSY' '3D C(CO)NH' 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 APTX _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 1 153 3 HIS CA C 63.0302 0.0000 1 2 153 3 HIS CB C 32.0161 0.0000 1 3 154 4 MET H H 8.1600 0.0000 1 4 154 4 MET CA C 61.0067 0.0000 1 5 154 4 MET CB C 38.7703 0.0000 1 6 154 4 MET N N 121.1648 0.0000 1 7 155 5 LYS H H 8.3736 0.0000 1 8 155 5 LYS CB C 32.9512 0.0000 1 9 155 5 LYS N N 126.2925 0.0000 1 10 156 6 ASP H H 8.2749 0.0000 1 11 156 6 ASP CA C 54.2725 0.0000 1 12 156 6 ASP CB C 41.1649 0.0000 1 13 156 6 ASP N N 120.9788 0.0000 1 14 157 7 ALA H H 8.0798 0.0000 1 15 157 7 ALA CA C 50.7472 0.0000 1 16 157 7 ALA CB C 18.3621 0.0000 1 17 157 7 ALA N N 125.1935 0.0000 1 18 165 15 GLY CA C 45.7500 0.0000 1 19 166 16 HIS H H 8.4259 0.0000 1 20 166 16 HIS CA C 60.2249 0.0000 1 21 166 16 HIS CB C 31.0155 0.0000 1 22 166 16 HIS N N 120.1161 0.0000 1 23 167 17 TRP H H 8.0825 0.0000 1 24 167 17 TRP CA C 58.1096 0.0000 1 25 167 17 TRP N N 119.0452 0.0000 1 26 168 18 SER H H 9.1441 0.0000 1 27 168 18 SER CA C 54.4567 0.0000 1 28 168 18 SER N N 119.5912 0.0000 1 29 169 19 GLN H H 7.2012 0.0000 1 30 169 19 GLN CA C 56.0217 0.0000 1 31 169 19 GLN N N 122.4534 0.0000 1 32 171 21 LEU CA C 57.4860 0.0000 1 33 171 21 LEU CB C 42.1401 0.0000 1 34 172 22 LYS H H 8.0032 0.0000 1 35 172 22 LYS CA C 59.2558 0.0000 1 36 172 22 LYS CB C 32.0391 0.0000 1 37 172 22 LYS N N 118.2848 0.0000 1 38 173 23 ILE H H 7.6490 0.0000 1 39 173 23 ILE CA C 63.4221 0.0000 1 40 173 23 ILE CB C 37.9711 0.0000 1 41 173 23 ILE N N 117.7872 0.0000 1 42 174 24 SER CA C 61.8591 0.0000 1 43 174 24 SER CB C 63.4992 0.0000 1 44 175 25 MET H H 8.0784 0.0000 1 45 175 25 MET CA C 57.9994 0.0000 1 46 175 25 MET CB C 33.7506 0.0000 1 47 175 25 MET N N 116.8767 0.0000 1 48 176 26 GLN H H 7.3041 0.0000 1 49 176 26 GLN CA C 55.7495 0.0000 1 50 176 26 GLN CB C 29.7508 0.0000 1 51 176 26 GLN N N 113.1744 0.0000 1 52 177 27 ASP H H 8.3473 0.0000 1 53 177 27 ASP CA C 52.9997 0.0000 1 54 177 27 ASP CB C 40.7502 0.0000 1 55 177 27 ASP N N 123.3556 0.0000 1 56 178 28 PRO CA C 64.6394 0.0000 1 57 178 28 PRO CB C 32.3309 0.0000 1 58 179 29 LYS H H 8.2867 0.0000 1 59 179 29 LYS CA C 58.0603 0.0000 1 60 179 29 LYS CB C 31.8903 0.0000 1 61 179 29 LYS N N 115.3816 0.0000 1 62 180 30 MET H H 7.8924 0.0000 1 63 180 30 MET CA C 54.3266 0.0000 1 64 180 30 MET CB C 33.2222 0.0000 1 65 180 30 MET N N 115.1293 0.0000 1 66 181 31 GLN H H 7.0933 0.0000 1 67 181 31 GLN CA C 55.8392 0.0000 1 68 181 31 GLN CB C 28.2508 0.0000 1 69 181 31 GLN N N 117.7456 0.0000 1 70 182 32 VAL H H 8.9400 0.0000 1 71 182 32 VAL CA C 62.9182 0.0000 1 72 182 32 VAL CB C 32.7467 0.0000 1 73 182 32 VAL N N 124.3347 0.0000 1 74 183 33 TYR H H 7.3981 0.0000 1 75 183 33 TYR CA C 57.4152 0.0000 1 76 183 33 TYR CB C 41.4792 0.0000 1 77 183 33 TYR N N 118.8629 0.0000 1 78 184 34 LYS H H 7.4626 0.0000 1 79 184 34 LYS CA C 56.2606 0.0000 1 80 184 34 LYS CB C 35.9634 0.0000 1 81 184 34 LYS N N 126.0718 0.0000 1 82 185 35 ASP H H 9.3176 0.0000 1 83 185 35 ASP CA C 53.5825 0.0000 1 84 185 35 ASP CB C 40.9856 0.0000 1 85 185 35 ASP N N 122.9915 0.0000 1 86 186 36 GLU H H 8.9169 0.0000 1 87 186 36 GLU CA C 58.7899 0.0000 1 88 186 36 GLU CB C 29.2130 0.0000 1 89 186 36 GLU N N 116.0006 0.0000 1 90 187 37 GLN H H 9.5839 0.0000 1 91 187 37 GLN CA C 58.3704 0.0000 1 92 187 37 GLN CB C 33.2506 0.0000 1 93 187 37 GLN N N 117.4022 0.0000 1 94 188 38 VAL H H 8.9579 0.0000 1 95 188 38 VAL CA C 57.9655 0.0000 1 96 188 38 VAL CB C 37.4625 0.0000 1 97 188 38 VAL N N 114.6768 0.0000 1 98 189 39 VAL H H 8.5596 0.0000 1 99 189 39 VAL CA C 59.2159 0.0000 1 100 189 39 VAL CB C 35.5820 0.0000 1 101 189 39 VAL N N 117.4429 0.0000 1 102 190 40 VAL H H 8.7072 0.0000 1 103 190 40 VAL CA C 59.8175 0.0000 1 104 190 40 VAL CB C 33.4497 0.0000 1 105 190 40 VAL N N 125.1506 0.0000 1 106 192 42 LYS CA C 57.1643 0.0000 1 107 192 42 LYS CB C 32.9811 0.0000 1 108 193 43 ASP H H 7.6754 0.0000 1 109 193 43 ASP CA C 55.7516 0.0000 1 110 193 43 ASP CB C 41.9420 0.0000 1 111 193 43 ASP N N 124.2689 0.0000 1 112 194 44 LYS H H 7.5152 0.0000 1 113 194 44 LYS CA C 58.1096 0.0000 1 114 194 44 LYS CB C 33.0006 0.0000 1 115 194 44 LYS N N 126.1486 0.0000 1 116 195 45 TYR H H 9.0931 0.0000 1 117 195 45 TYR CA C 53.9754 0.0000 1 118 195 45 TYR CB C 38.5003 0.0000 1 119 195 45 TYR N N 119.6287 0.0000 1 120 196 46 PRO CA C 61.9881 0.0000 1 121 196 46 PRO CB C 33.2506 0.0000 1 122 197 47 LYS H H 11.6619 0.0000 1 123 197 47 LYS CA C 54.2122 0.0000 1 124 197 47 LYS CB C 30.4782 0.0000 1 125 197 47 LYS N N 126.6157 0.0000 1 126 198 48 ALA H H 7.1146 0.0000 1 127 198 48 ALA CA C 50.6123 0.0000 1 128 198 48 ALA CB C 24.5228 0.0000 1 129 198 48 ALA N N 114.0669 0.0000 1 130 199 49 ARG H H 9.8280 0.0000 1 131 199 49 ARG CA C 60.0553 0.0000 1 132 199 49 ARG CB C 30.4255 0.0000 1 133 199 49 ARG N N 121.1437 0.0000 1 134 200 50 TYR H H 7.9889 0.0000 1 135 200 50 TYR CA C 56.5488 0.0000 1 136 200 50 TYR CB C 40.2630 0.0000 1 137 200 50 TYR N N 115.3602 0.0000 1 138 201 51 HIS H H 7.7515 0.0000 1 139 201 51 HIS CA C 53.8711 0.0000 1 140 201 51 HIS CB C 33.5081 0.0000 1 141 201 51 HIS N N 122.0240 0.0000 1 142 202 52 TRP H H 9.6797 0.0000 1 143 202 52 TRP CA C 57.7498 0.0000 1 144 202 52 TRP CB C 32.0006 0.0000 1 145 202 52 TRP N N 126.5037 0.0000 1 146 203 53 LEU H H 9.2675 0.0000 1 147 203 53 LEU CA C 52.4997 0.0000 1 148 203 53 LEU CB C 43.7741 0.0000 1 149 203 53 LEU N N 119.0282 0.0000 1 150 204 54 VAL H H 9.5041 0.0000 1 151 204 54 VAL CA C 61.5123 0.0000 1 152 204 54 VAL CB C 31.5007 0.0000 1 153 204 54 VAL N N 122.0531 0.0000 1 154 205 55 LEU H H 9.2588 0.0000 1 155 205 55 LEU CA C 52.1289 0.0000 1 156 205 55 LEU CB C 43.2723 0.0000 1 157 205 55 LEU N N 127.0272 0.0000 1 158 206 56 PRO CA C 61.2116 0.0000 1 159 206 56 PRO CB C 32.0596 0.0000 1 160 207 57 TRP H H 7.6530 0.0000 1 161 207 57 TRP CA C 59.4749 0.0000 1 162 207 57 TRP CB C 29.7514 0.0000 1 163 207 57 TRP N N 120.4246 0.0000 1 164 208 58 THR H H 8.2257 0.0000 1 165 208 58 THR CA C 62.5550 0.0000 1 166 208 58 THR CB C 69.5411 0.0000 1 167 208 58 THR N N 115.1516 0.0000 1 168 209 59 SER H H 8.2887 0.0000 1 169 209 59 SER CA C 58.3838 0.0000 1 170 209 59 SER CB C 63.2979 0.0000 1 171 209 59 SER N N 120.1777 0.0000 1 172 210 60 ILE H H 8.2969 0.0000 1 173 210 60 ILE CA C 60.8444 0.0000 1 174 210 60 ILE N N 128.8937 0.0000 1 175 211 61 SER H H 8.7870 0.0000 1 176 211 61 SER CA C 61.5947 0.0000 1 177 211 61 SER CB C 63.4625 0.0000 1 178 211 61 SER N N 121.1277 0.0000 1 179 212 62 SER H H 7.1165 0.0000 1 180 212 62 SER CA C 57.5640 0.0000 1 181 212 62 SER CB C 65.2239 0.0000 1 182 212 62 SER N N 109.9012 0.0000 1 183 214 64 LYS CA C 58.4939 0.0000 1 184 214 64 LYS CB C 32.0650 0.0000 1 185 215 65 ALA H H 7.2913 0.0000 1 186 215 65 ALA CA C 51.4134 0.0000 1 187 215 65 ALA CB C 19.7230 0.0000 1 188 215 65 ALA N N 119.8716 0.0000 1 189 216 66 VAL H H 6.7217 0.0000 1 190 216 66 VAL CA C 62.8893 0.0000 1 191 216 66 VAL CB C 31.5007 0.0000 1 192 216 66 VAL N N 118.9481 0.0000 1 193 217 67 ALA H H 11.4644 0.0000 1 194 217 67 ALA CA C 50.8405 0.0000 1 195 217 67 ALA CB C 23.0552 0.0000 1 196 217 67 ALA N N 134.61 0.0000 1 197 218 68 ARG H H 8.4700 0.0000 1 198 218 68 ARG CA C 60.7493 0.0000 1 199 218 68 ARG CB C 29.5008 0.0000 1 200 218 68 ARG N N 119.9968 0.0000 1 201 219 69 GLU H H 9.0621 0.0000 1 202 219 69 GLU CA C 58.3965 0.0000 1 203 219 69 GLU CB C 28.3207 0.0000 1 204 219 69 GLU N N 117.3394 0.0000 1 205 220 70 HIS H H 8.0885 0.0000 1 206 220 70 HIS CA C 57.7323 0.0000 1 207 220 70 HIS CB C 32.0635 0.0000 1 208 220 70 HIS N N 119.5333 0.0000 1 209 221 71 LEU H H 7.8753 0.0000 1 210 221 71 LEU CA C 59.5303 0.0000 1 211 221 71 LEU CB C 42.5002 0.0000 1 212 221 71 LEU N N 121.3986 0.0000 1 213 222 72 GLU H H 8.5619 0.0000 1 214 222 72 GLU CA C 60.0748 0.0000 1 215 222 72 GLU CB C 28.2615 0.0000 1 216 222 72 GLU N N 116.2626 0.0000 1 217 223 73 LEU H H 8.1024 0.0000 1 218 223 73 LEU CA C 58.2024 0.0000 1 219 223 73 LEU CB C 41.5002 0.0000 1 220 223 73 LEU N N 124.3060 0.0000 1 221 224 74 LEU H H 8.5547 0.0000 1 222 224 74 LEU CA C 58.4071 0.0000 1 223 224 74 LEU CB C 42.0138 0.0000 1 224 224 74 LEU N N 119.8291 0.0000 1 225 225 75 LYS H H 8.8849 0.0000 1 226 225 75 LYS CA C 57.2063 0.0000 1 227 225 75 LYS CB C 33.0006 0.0000 1 228 225 75 LYS N N 122.0216 0.0000 1 229 226 76 HIS H H 8.0839 0.0000 1 230 226 76 HIS CB C 31.2798 0.0000 1 231 226 76 HIS N N 121.0417 0.0000 1 232 227 77 MET H H 9.0965 0.0000 1 233 227 77 MET CA C 60.7124 0.0000 1 234 227 77 MET N N 117.3721 0.0000 1 235 228 78 HIS H H 7.4967 0.0000 1 236 228 78 HIS CA C 60.9993 0.0000 1 237 228 78 HIS CB C 32.2506 0.0000 1 238 228 78 HIS N N 117.7486 0.0000 1 239 229 79 THR H H 8.2028 0.0000 1 240 229 79 THR CA C 66.5178 0.0000 1 241 229 79 THR CB C 68.8141 0.0000 1 242 229 79 THR N N 115.0255 0.0000 1 243 230 80 VAL H H 8.4994 0.0000 1 244 230 80 VAL CA C 66.5460 0.0000 1 245 230 80 VAL CB C 31.0007 0.0000 1 246 230 80 VAL N N 123.3335 0.0000 1 247 231 81 GLY H H 8.1679 0.0000 1 248 231 81 GLY CA C 48.1184 0.0000 1 249 231 81 GLY N N 108.3271 0.0000 1 250 232 82 GLU H H 7.8651 0.0000 1 251 232 82 GLU CA C 59.7402 0.0000 1 252 232 82 GLU CB C 29.4957 0.0000 1 253 232 82 GLU N N 117.2237 0.0000 1 254 233 83 LYS H H 7.6750 0.0000 1 255 233 83 LYS CA C 58.8196 0.0000 1 256 233 83 LYS CB C 32.2659 0.0000 1 257 233 83 LYS N N 121.9336 0.0000 1 258 234 84 VAL H H 7.9772 0.0000 1 259 234 84 VAL CA C 66.0560 0.0000 1 260 234 84 VAL CB C 30.7507 0.0000 1 261 234 84 VAL N N 118.6432 0.0000 1 262 235 85 ILE H H 6.8838 0.0000 1 263 235 85 ILE CA C 65.9009 0.0000 1 264 235 85 ILE CB C 37.5004 0.0000 1 265 235 85 ILE N N 118.5925 0.0000 1 266 236 86 VAL H H 6.9344 0.0000 1 267 236 86 VAL CA C 66.2491 0.0000 1 268 236 86 VAL CB C 31.7367 0.0000 1 269 236 86 VAL N N 117.9164 0.0000 1 270 237 87 ASP H H 8.4103 0.0000 1 271 237 87 ASP CA C 56.9094 0.0000 1 272 237 87 ASP CB C 40.3220 0.0000 1 273 237 87 ASP N N 119.1545 0.0000 1 274 238 88 PHE H H 8.2208 0.0000 1 275 238 88 PHE CA C 59.2063 0.0000 1 276 238 88 PHE CB C 40.6800 0.0000 1 277 238 88 PHE N N 114.5140 0.0000 1 278 239 89 ALA H H 8.3167 0.0000 1 279 239 89 ALA CA C 52.1022 0.0000 1 280 239 89 ALA CB C 19.4171 0.0000 1 281 239 89 ALA N N 123.3776 0.0000 1 282 240 90 GLY H H 7.9823 0.0000 1 283 240 90 GLY CA C 47.7370 0.0000 1 284 240 90 GLY N N 109.8643 0.0000 1 285 243 93 LYS CA C 56.8634 0.0000 1 286 243 93 LYS CB C 30.7564 0.0000 1 287 244 94 LEU H H 7.7348 0.0000 1 288 244 94 LEU CA C 54.6130 0.0000 1 289 244 94 LEU CB C 43.9957 0.0000 1 290 244 94 LEU N N 120.4925 0.0000 1 291 245 95 ARG H H 8.1484 0.0000 1 292 245 95 ARG CA C 55.2968 0.0000 1 293 245 95 ARG N N 120.4147 0.0000 1 294 246 96 PHE H H 8.7377 0.0000 1 295 246 96 PHE CA C 57.3551 0.0000 1 296 246 96 PHE CB C 45.2074 0.0000 1 297 246 96 PHE N N 119.6533 0.0000 1 298 247 97 ARG H H 8.4402 0.0000 1 299 247 97 ARG CA C 56.1676 0.0000 1 300 247 97 ARG CB C 35.4934 0.0000 1 301 247 97 ARG N N 116.4422 0.0000 1 302 248 98 LEU H H 9.0787 0.0000 1 303 248 98 LEU CA C 54.3184 0.0000 1 304 248 98 LEU CB C 44.1627 0.0000 1 305 248 98 LEU N N 121.9583 0.0000 1 306 249 99 GLY H H 9.0005 0.0000 1 307 249 99 GLY CA C 46.8966 0.0000 1 308 249 99 GLY N N 111.0586 0.0000 1 309 250 100 TYR H H 8.7736 0.0000 1 310 250 100 TYR CA C 56.7495 0.0000 1 311 250 100 TYR N N 116.3837 0.0000 1 312 251 101 HIS H H 8.5716 0.0000 1 313 251 101 HIS CA C 55.1630 0.0000 1 314 251 101 HIS N N 119.5840 0.0000 1 315 252 102 ALA H H 8.5039 0.0000 1 316 252 102 ALA CA C 54.4546 0.0000 1 317 252 102 ALA CB C 18.9791 0.0000 1 318 252 102 ALA N N 122.7980 0.0000 1 319 253 103 ILE H H 6.1241 0.0000 1 320 253 103 ILE CA C 57.2099 0.0000 1 321 253 103 ILE CB C 39.0003 0.0000 1 322 253 103 ILE N N 112.8320 0.0000 1 323 260 110 HIS CA C 56.0615 0.0000 1 324 260 110 HIS CB C 33.0084 0.0000 1 325 261 111 LEU H H 8.4192 0.0000 1 326 261 111 LEU CA C 54.1758 0.0000 1 327 261 111 LEU CB C 45.1316 0.0000 1 328 261 111 LEU N N 124.2664 0.0000 1 329 262 112 HIS H H 9.4809 0.0000 1 330 262 112 HIS CA C 57.2652 0.0000 1 331 262 112 HIS CB C 34.5005 0.0000 1 332 262 112 HIS N N 125.3005 0.0000 1 333 263 113 VAL H H 9.3664 0.0000 1 334 263 113 VAL CA C 62.2764 0.0000 1 335 263 113 VAL CB C 33.1464 0.0000 1 336 263 113 VAL N N 123.4218 0.0000 1 337 264 114 ILE H H 8.9796 0.0000 1 338 264 114 ILE CA C 58.4022 0.0000 1 339 264 114 ILE N N 123.2941 0.0000 1 340 265 115 SER H H 8.7694 0.0000 1 341 265 115 SER CA C 58.8128 0.0000 1 342 265 115 SER CB C 62.9992 0.0000 1 343 265 115 SER N N 128.5566 0.0000 1 344 266 116 GLN H H 7.5066 0.0000 1 345 266 116 GLN CA C 55.2069 0.0000 1 346 266 116 GLN N N 110.4240 0.0000 1 347 267 117 ASP H H 9.2116 0.0000 1 348 267 117 ASP CA C 54.7923 0.0000 1 349 267 117 ASP CB C 40.6689 0.0000 1 350 267 117 ASP N N 117.1495 0.0000 1 351 268 118 PHE H H 5.9110 0.0000 1 352 268 118 PHE CA C 60.6597 0.0000 1 353 268 118 PHE CB C 37.7420 0.0000 1 354 268 118 PHE N N 106.8059 0.0000 1 355 269 119 ASP H H 9.0831 0.0000 1 356 269 119 ASP CA C 52.2181 0.0000 1 357 269 119 ASP CB C 40.0463 0.0000 1 358 269 119 ASP N N 117.5764 0.0000 1 359 270 120 SER H H 7.3511 0.0000 1 360 270 120 SER CA C 53.3492 0.0000 1 361 270 120 SER CB C 65.2434 0.0000 1 362 270 120 SER N N 113.0822 0.0000 1 363 271 121 PRO CA C 63.6397 0.0000 1 364 271 121 PRO CB C 32.2037 0.0000 1 365 272 122 CYS H H 7.9586 0.0000 1 366 272 122 CYS CA C 59.3179 0.0000 1 367 272 122 CYS CB C 26.7838 0.0000 1 368 272 122 CYS N N 114.4195 0.0000 1 369 273 123 LEU H H 7.0943 0.0000 1 370 273 123 LEU CA C 55.7635 0.0000 1 371 273 123 LEU CB C 41.2502 0.0000 1 372 273 123 LEU N N 121.4285 0.0000 1 373 274 124 LYS H H 10.3126 0.0000 1 374 274 124 LYS CA C 57.1316 0.0000 1 375 274 124 LYS N N 127.1914 0.0000 1 376 275 125 ASN H H 8.1132 0.0000 1 377 275 125 ASN CA C 52.1139 0.0000 1 378 275 125 ASN CB C 41.2451 0.0000 1 379 275 125 ASN N N 117.1192 0.0000 1 380 278 128 HIS CA C 58.0888 0.0000 1 381 278 128 HIS CB C 33.3074 0.0000 1 382 279 129 TRP H H 7.6218 0.0000 1 383 279 129 TRP CA C 60.4845 0.0000 1 384 279 129 TRP CB C 30.5107 0.0000 1 385 279 129 TRP N N 115.6996 0.0000 1 386 280 130 ASN H H 9.1307 0.0000 1 387 280 130 ASN CA C 55.1317 0.0000 1 388 280 130 ASN CB C 39.0003 0.0000 1 389 280 130 ASN N N 116.3048 0.0000 1 390 281 131 SER H H 8.0192 0.0000 1 391 281 131 SER CA C 60.6881 0.0000 1 392 281 131 SER CB C 61.9993 0.0000 1 393 281 131 SER N N 117.0323 0.0000 1 394 282 132 PHE H H 6.4909 0.0000 1 395 282 132 PHE CA C 59.0795 0.0000 1 396 282 132 PHE CB C 42.6773 0.0000 1 397 282 132 PHE N N 112.7116 0.0000 1 398 283 133 ASN H H 6.7668 0.0000 1 399 283 133 ASN CA C 54.5572 0.0000 1 400 283 133 ASN CB C 39.9173 0.0000 1 401 283 133 ASN N N 114.0801 0.0000 1 402 284 134 THR H H 7.1500 0.0000 1 403 284 134 THR CA C 60.9638 0.0000 1 404 284 134 THR N N 107.7714 0.0000 1 405 285 135 GLU H H 9.2959 0.0000 1 406 285 135 GLU CA C 58.7705 0.0000 1 407 285 135 GLU CB C 28.7760 0.0000 1 408 285 135 GLU N N 119.8893 0.0000 1 409 286 136 TYR H H 7.8335 0.0000 1 410 286 136 TYR CA C 60.2141 0.0000 1 411 286 136 TYR CB C 40.2237 0.0000 1 412 286 136 TYR N N 119.6775 0.0000 1 413 287 137 PHE H H 7.8661 0.0000 1 414 287 137 PHE CA C 56.4592 0.0000 1 415 287 137 PHE CB C 38.8490 0.0000 1 416 287 137 PHE N N 117.4815 0.0000 1 417 288 138 LEU H H 9.0797 0.0000 1 418 288 138 LEU CA C 54.1003 0.0000 1 419 288 138 LEU CB C 43.3935 0.0000 1 420 288 138 LEU N N 129.0042 0.0000 1 421 289 139 GLU H H 8.8356 0.0000 1 422 289 139 GLU CA C 57.6405 0.0000 1 423 289 139 GLU CB C 29.9908 0.0000 1 424 289 139 GLU N N 123.4455 0.0000 1 425 290 140 SER H H 9.1483 0.0000 1 426 290 140 SER CA C 61.7739 0.0000 1 427 290 140 SER N N 120.1808 0.0000 1 428 291 141 GLN H H 9.1969 0.0000 1 429 291 141 GLN CA C 58.8741 0.0000 1 430 291 141 GLN CB C 27.9699 0.0000 1 431 291 141 GLN N N 114.3181 0.0000 1 432 292 142 ALA H H 6.9213 0.0000 1 433 292 142 ALA CA C 54.9612 0.0000 1 434 292 142 ALA CB C 18.0447 0.0000 1 435 292 142 ALA N N 120.1644 0.0000 1 436 293 143 VAL H H 8.1029 0.0000 1 437 293 143 VAL CA C 67.4883 0.0000 1 438 293 143 VAL N N 121.5952 0.0000 1 439 294 144 ILE H H 8.4198 0.0000 1 440 294 144 ILE CA C 66.6053 0.0000 1 441 294 144 ILE CB C 38.5021 0.0000 1 442 294 144 ILE N N 119.8764 0.0000 1 443 295 145 GLU H H 7.9633 0.0000 1 444 295 145 GLU CA C 59.7901 0.0000 1 445 295 145 GLU CB C 29.4083 0.0000 1 446 295 145 GLU N N 117.7606 0.0000 1 447 296 146 MET H H 8.1524 0.0000 1 448 296 146 MET CA C 60.1567 0.0000 1 449 296 146 MET CB C 33.7052 0.0000 1 450 296 146 MET N N 119.3057 0.0000 1 451 297 147 VAL H H 8.0573 0.0000 1 452 297 147 VAL CA C 66.8255 0.0000 1 453 297 147 VAL CB C 30.6107 0.0000 1 454 297 147 VAL N N 119.0543 0.0000 1 455 298 148 GLN H H 8.7474 0.0000 1 456 298 148 GLN CA C 59.7144 0.0000 1 457 298 148 GLN CB C 29.2819 0.0000 1 458 298 148 GLN N N 119.8026 0.0000 1 459 299 149 GLU H H 8.3155 0.0000 1 460 299 149 GLU CA C 58.5787 0.0000 1 461 299 149 GLU CB C 30.5748 0.0000 1 462 299 149 GLU N N 117.2763 0.0000 1 463 300 150 ALA H H 8.6040 0.0000 1 464 300 150 ALA CA C 52.2005 0.0000 1 465 300 150 ALA CB C 21.2509 0.0000 1 466 300 150 ALA N N 119.7719 0.0000 1 467 301 151 GLY H H 8.2576 0.0000 1 468 301 151 GLY CA C 46.1472 0.0000 1 469 301 151 GLY N N 108.8129 0.0000 1 470 302 152 ARG H H 7.2108 0.0000 1 471 302 152 ARG CA C 54.1578 0.0000 1 472 302 152 ARG CB C 32.0852 0.0000 1 473 302 152 ARG N N 112.5640 0.0000 1 474 303 153 VAL H H 9.6609 0.0000 1 475 303 153 VAL CA C 62.0002 0.0000 1 476 303 153 VAL CB C 32.7702 0.0000 1 477 303 153 VAL N N 122.5849 0.0000 1 478 304 154 THR H H 7.8497 0.0000 1 479 304 154 THR CA C 62.7219 0.0000 1 480 304 154 THR CB C 69.1813 0.0000 1 481 304 154 THR N N 125.5914 0.0000 1 482 305 155 VAL H H 8.3472 0.0000 1 483 305 155 VAL CA C 60.9922 0.0000 1 484 305 155 VAL CB C 33.2377 0.0000 1 485 305 155 VAL N N 127.4397 0.0000 1 486 306 156 ARG H H 8.6251 0.0000 1 487 306 156 ARG CA C 56.4995 0.0000 1 488 306 156 ARG CB C 30.7507 0.0000 1 489 306 156 ARG N N 127.5964 0.0000 1 490 307 157 ASP H H 8.3498 0.0000 1 491 307 157 ASP CA C 55.2732 0.0000 1 492 307 157 ASP CB C 41.5002 0.0000 1 493 307 157 ASP N N 120.1161 0.0000 1 494 310 160 PRO CA C 66.2676 0.0000 1 495 310 160 PRO CB C 30.8870 0.0000 1 496 311 161 GLU H H 7.7737 0.0000 1 497 311 161 GLU CA C 58.6390 0.0000 1 498 311 161 GLU CB C 28.7508 0.0000 1 499 311 161 GLU N N 115.4115 0.0000 1 500 312 162 LEU H H 7.9827 0.0000 1 501 312 162 LEU CA C 57.0257 0.0000 1 502 312 162 LEU CB C 40.9681 0.0000 1 503 312 162 LEU N N 120.5927 0.0000 1 504 313 163 LEU H H 7.0410 0.0000 1 505 313 163 LEU CA C 56.0232 0.0000 1 506 313 163 LEU CB C 40.7357 0.0000 1 507 313 163 LEU N N 111.2633 0.0000 1 508 314 164 LYS H H 7.3495 0.0000 1 509 314 164 LYS CA C 55.7915 0.0000 1 510 314 164 LYS CB C 33.1901 0.0000 1 511 314 164 LYS N N 117.8055 0.0000 1 512 315 165 LEU H H 6.9746 0.0000 1 513 315 165 LEU CA C 54.8542 0.0000 1 514 315 165 LEU CB C 41.0071 0.0000 1 515 315 165 LEU N N 122.7961 0.0000 1 516 316 166 PRO CA C 62.8453 0.0000 1 517 316 166 PRO CB C 32.5759 0.0000 1 518 317 167 LEU H H 8.5131 0.0000 1 519 317 167 LEU CA C 55.6079 0.0000 1 520 317 167 LEU CB C 41.8025 0.0000 1 521 317 167 LEU N N 122.4824 0.0000 1 522 318 168 ARG H H 7.6148 0.0000 1 523 318 168 ARG CA C 54.0252 0.0000 1 524 318 168 ARG CB C 33.7506 0.0000 1 525 318 168 ARG N N 122.0435 0.0000 1 526 319 169 CYS H H 8.6005 0.0000 1 527 319 169 CYS CA C 61.5208 0.0000 1 528 319 169 CYS CB C 30.2881 0.0000 1 529 319 169 CYS N N 126.7225 0.0000 1 530 320 170 HIS CA C 58.6052 0.0000 1 531 320 170 HIS CB C 30.4966 0.0000 1 532 321 171 GLU H H 9.1567 0.0000 1 533 321 171 GLU CA C 57.5997 0.0000 1 534 321 171 GLU CB C 29.2508 0.0000 1 535 321 171 GLU N N 125.7264 0.0000 1 536 322 172 CYS H H 8.2639 0.0000 1 537 322 172 CYS CA C 58.6025 0.0000 1 538 322 172 CYS CB C 31.9847 0.0000 1 539 322 172 CYS N N 117.0643 0.0000 1 540 323 173 GLN H H 7.4733 0.0000 1 541 323 173 GLN CA C 58.6377 0.0000 1 542 323 173 GLN CB C 25.6548 0.0000 1 543 323 173 GLN N N 114.9037 0.0000 1 544 324 174 GLN H H 7.8562 0.0000 1 545 324 174 GLN CA C 57.5923 0.0000 1 546 324 174 GLN CB C 30.0546 0.0000 1 547 324 174 GLN N N 121.5435 0.0000 1 548 325 175 LEU H H 8.3473 0.0000 1 549 325 175 LEU CA C 54.9429 0.0000 1 550 325 175 LEU CB C 42.9913 0.0000 1 551 325 175 LEU N N 125.2472 0.0000 1 552 326 176 LEU H H 8.3908 0.0000 1 553 326 176 LEU CB C 44.2479 0.0000 1 554 326 176 LEU N N 126.6403 0.0000 1 555 327 177 PRO CA C 64.3000 0.0000 1 556 327 177 PRO CB C 32.7000 0.0000 1 557 328 178 SER H H 6.7978 0.0000 1 558 328 178 SER CA C 56.3500 0.0000 1 559 328 178 SER CB C 66.1000 0.0000 1 560 328 178 SER N N 109.0388 0.0000 1 561 330 180 PRO CA C 66.6125 0.0000 1 562 330 180 PRO CB C 31.0657 0.0000 1 563 331 181 GLN H H 7.1690 0.0000 1 564 331 181 GLN CA C 58.9542 0.0000 1 565 331 181 GLN CB C 28.7921 0.0000 1 566 331 181 GLN N N 114.0161 0.0000 1 567 332 182 LEU H H 8.3177 0.0000 1 568 332 182 LEU CA C 58.8686 0.0000 1 569 332 182 LEU CB C 41.8078 0.0000 1 570 332 182 LEU N N 124.6774 0.0000 1 571 333 183 LYS H H 8.6633 0.0000 1 572 333 183 LYS CA C 60.7694 0.0000 1 573 333 183 LYS CB C 32.3162 0.0000 1 574 333 183 LYS N N 118.3350 0.0000 1 575 334 184 GLU H H 7.3816 0.0000 1 576 334 184 GLU CA C 58.9012 0.0000 1 577 334 184 GLU CB C 29.7585 0.0000 1 578 334 184 GLU N N 117.3271 0.0000 1 579 335 185 HIS H H 7.9504 0.0000 1 580 335 185 HIS CA C 59.9759 0.0000 1 581 335 185 HIS CB C 28.4570 0.0000 1 582 335 185 HIS N N 119.9638 0.0000 1 583 336 186 LEU H H 8.5961 0.0000 1 584 336 186 LEU CA C 58.1100 0.0000 1 585 336 186 LEU CB C 41.9252 0.0000 1 586 336 186 LEU N N 117.5132 0.0000 1 587 337 187 ARG H H 6.6272 0.0000 1 588 337 187 ARG CA C 58.1430 0.0000 1 589 337 187 ARG CB C 29.7507 0.0000 1 590 337 187 ARG N N 114.1551 0.0000 1 591 338 188 LYS H H 7.3528 0.0000 1 592 338 188 LYS CA C 57.9656 0.0000 1 593 338 188 LYS CB C 31.2654 0.0000 1 594 338 188 LYS N N 116.5776 0.0000 1 595 339 189 HIS H H 7.4116 0.0000 1 596 339 189 HIS CA C 55.6076 0.0000 1 597 339 189 HIS CB C 28.6370 0.0000 1 598 339 189 HIS N N 114.9615 0.0000 1 599 340 190 TRP H H 7.3527 0.0000 1 600 340 190 TRP CA C 55.9569 0.0000 1 601 340 190 TRP CB C 29.5978 0.0000 1 602 340 190 TRP N N 120.2417 0.0000 1 603 341 191 THR H H 8.0727 0.0000 1 604 341 191 THR CA C 61.8558 0.0000 1 605 341 191 THR CB C 70.0213 0.0000 1 606 341 191 THR N N 114.3287 0.0000 1 607 342 192 GLN H H 8.0035 0.0000 1 608 342 192 GLN CA C 57.6911 0.0000 1 609 342 192 GLN CB C 30.4224 0.0000 1 610 342 192 GLN N N 127.5105 0.0000 1 stop_ save_