data_17341 ####################### # Entry information # ####################### save_entry_information _Saveframe_category entry_information _Entry_title ; 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine as a Substrate of Cytochrome P450 2D6: Allosteric Effects of NADPH-Cytochrome P450 Reductase ; _BMRB_accession_number 17341 _BMRB_flat_file_name bmr17341.str _Entry_type original _Submission_date 2010-12-02 _Accession_date 2010-12-02 _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 Modi S. . . 2 Gilham D. E. . 3 Sutclffe M. J. . 4 Lian L.Y. . . 5 Primrose W. U. . 6 Wolf C. R. . 7 Roberts G. C.K. . stop_ loop_ _Saveframe_category_type _Saveframe_category_type_count binding_constants 1 stop_ loop_ _Revision_date _Revision_keyword _Revision_author _Revision_detail 2012-06-06 original author . stop_ _Original_release_date 2012-06-06 save_ ############################# # Citation for this entry # ############################# save_entry_citation _Saveframe_category entry_citation _Citation_full . _Citation_title '1-Methyl-4-phenyl-1,2,3,6-tetrahydrophyridine as a Substrate of Cytochrome P450 2D6: Allosteric Effects of NADPH-Cytochrome P450 Reductase' _Citation_status published _Citation_type journal _CAS_abstract_code . _MEDLINE_UI_code . _PubMed_ID ? loop_ _Author_ordinal _Author_family_name _Author_given_name _Author_middle_initials _Author_family_title 1 Modi S. . . 2 Gilham D. E. . 3 Sutclffe M. J. . 4 Lian L.Y. . . 5 Primrose W. U. . 6 Wolf C. R. . 7 Roberts G. C.K. . stop_ _Journal_abbreviation Biochemistry _Journal_volume 36 _Journal_issue . _Journal_CSD . _Book_chapter_title . _Book_volume . _Book_series . _Book_ISBN . _Conference_state_province . _Conference_abstract_number . _Page_first 4461 _Page_last 4470 _Year 1997 _Details . save_ ################################## # Molecular system description # ################################## save_assembly _Saveframe_category molecular_system _Mol_system_name 'CYP 2D6/MPTP complex' _Enzyme_commission_number . loop_ _Mol_system_component_name _Mol_label 'CYP 2D6' $CYP_2D6 MPTP $MPTP 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_CYP_2D6 _Saveframe_category monomeric_polymer _Mol_type polymer _Mol_polymer_class protein _Name_common CYP_2D6 _Molecular_mass . _Mol_thiol_state unknown _Details . ############################## # Polymer residue sequence # ############################## _Residue_count 479 _Mol_residue_sequence ; MAKKTSSKGKLPPGPLPLPG LGNLLHVDFQNTPYCFDQLR RRFGDVFSLQLAWTPVVVLN GLAAVREALVTHGEDTADRP PVPITQILGFGPRSQGVFLA RYGPAWREQRRFSVSTLRNL GLGKKSLEQWVTEEAACLCA AFANHSGRPFRPNGLLDKAV SNVIASLTCGRRFEYDDPRF LRLLDLAQEGLKEESGFLRE VLNAVPVDRHIPALAGKVLR FQKAFLTQLDELLTEHRMTW DPAQPPRDLTEAFLAEMEKA KGNPESSFNDENLRIVVADL FSAGMVTTSTTLAWGLLLMI LHPDVQRRVQQEIDDVIGQV RRPEMGDQAHMPYTTAVIHE VQRFGDIVPLGMTHMTSRDI EVQGFRIPKGTTLITNLSSV LKDEAVWEKPFRFHPEHFLD AQGHFVKPEAFLPFSAGRRA CLGEPLARMELFLFFTSLLQ HFSFSVPTGQPRPSHHGVFA FLVSPSPYELCAVPRHHHH ; loop_ _Residue_seq_code _Residue_label 1 MET 2 ALA 3 LYS 4 LYS 5 THR 6 SER 7 SER 8 LYS 9 GLY 10 LYS 11 LEU 12 PRO 13 PRO 14 GLY 15 PRO 16 LEU 17 PRO 18 LEU 19 PRO 20 GLY 21 LEU 22 GLY 23 ASN 24 LEU 25 LEU 26 HIS 27 VAL 28 ASP 29 PHE 30 GLN 31 ASN 32 THR 33 PRO 34 TYR 35 CYS 36 PHE 37 ASP 38 GLN 39 LEU 40 ARG 41 ARG 42 ARG 43 PHE 44 GLY 45 ASP 46 VAL 47 PHE 48 SER 49 LEU 50 GLN 51 LEU 52 ALA 53 TRP 54 THR 55 PRO 56 VAL 57 VAL 58 VAL 59 LEU 60 ASN 61 GLY 62 LEU 63 ALA 64 ALA 65 VAL 66 ARG 67 GLU 68 ALA 69 LEU 70 VAL 71 THR 72 HIS 73 GLY 74 GLU 75 ASP 76 THR 77 ALA 78 ASP 79 ARG 80 PRO 81 PRO 82 VAL 83 PRO 84 ILE 85 THR 86 GLN 87 ILE 88 LEU 89 GLY 90 PHE 91 GLY 92 PRO 93 ARG 94 SER 95 GLN 96 GLY 97 VAL 98 PHE 99 LEU 100 ALA 101 ARG 102 TYR 103 GLY 104 PRO 105 ALA 106 TRP 107 ARG 108 GLU 109 GLN 110 ARG 111 ARG 112 PHE 113 SER 114 VAL 115 SER 116 THR 117 LEU 118 ARG 119 ASN 120 LEU 121 GLY 122 LEU 123 GLY 124 LYS 125 LYS 126 SER 127 LEU 128 GLU 129 GLN 130 TRP 131 VAL 132 THR 133 GLU 134 GLU 135 ALA 136 ALA 137 CYS 138 LEU 139 CYS 140 ALA 141 ALA 142 PHE 143 ALA 144 ASN 145 HIS 146 SER 147 GLY 148 ARG 149 PRO 150 PHE 151 ARG 152 PRO 153 ASN 154 GLY 155 LEU 156 LEU 157 ASP 158 LYS 159 ALA 160 VAL 161 SER 162 ASN 163 VAL 164 ILE 165 ALA 166 SER 167 LEU 168 THR 169 CYS 170 GLY 171 ARG 172 ARG 173 PHE 174 GLU 175 TYR 176 ASP 177 ASP 178 PRO 179 ARG 180 PHE 181 LEU 182 ARG 183 LEU 184 LEU 185 ASP 186 LEU 187 ALA 188 GLN 189 GLU 190 GLY 191 LEU 192 LYS 193 GLU 194 GLU 195 SER 196 GLY 197 PHE 198 LEU 199 ARG 200 GLU 201 VAL 202 LEU 203 ASN 204 ALA 205 VAL 206 PRO 207 VAL 208 ASP 209 ARG 210 HIS 211 ILE 212 PRO 213 ALA 214 LEU 215 ALA 216 GLY 217 LYS 218 VAL 219 LEU 220 ARG 221 PHE 222 GLN 223 LYS 224 ALA 225 PHE 226 LEU 227 THR 228 GLN 229 LEU 230 ASP 231 GLU 232 LEU 233 LEU 234 THR 235 GLU 236 HIS 237 ARG 238 MET 239 THR 240 TRP 241 ASP 242 PRO 243 ALA 244 GLN 245 PRO 246 PRO 247 ARG 248 ASP 249 LEU 250 THR 251 GLU 252 ALA 253 PHE 254 LEU 255 ALA 256 GLU 257 MET 258 GLU 259 LYS 260 ALA 261 LYS 262 GLY 263 ASN 264 PRO 265 GLU 266 SER 267 SER 268 PHE 269 ASN 270 ASP 271 GLU 272 ASN 273 LEU 274 ARG 275 ILE 276 VAL 277 VAL 278 ALA 279 ASP 280 LEU 281 PHE 282 SER 283 ALA 284 GLY 285 MET 286 VAL 287 THR 288 THR 289 SER 290 THR 291 THR 292 LEU 293 ALA 294 TRP 295 GLY 296 LEU 297 LEU 298 LEU 299 MET 300 ILE 301 LEU 302 HIS 303 PRO 304 ASP 305 VAL 306 GLN 307 ARG 308 ARG 309 VAL 310 GLN 311 GLN 312 GLU 313 ILE 314 ASP 315 ASP 316 VAL 317 ILE 318 GLY 319 GLN 320 VAL 321 ARG 322 ARG 323 PRO 324 GLU 325 MET 326 GLY 327 ASP 328 GLN 329 ALA 330 HIS 331 MET 332 PRO 333 TYR 334 THR 335 THR 336 ALA 337 VAL 338 ILE 339 HIS 340 GLU 341 VAL 342 GLN 343 ARG 344 PHE 345 GLY 346 ASP 347 ILE 348 VAL 349 PRO 350 LEU 351 GLY 352 MET 353 THR 354 HIS 355 MET 356 THR 357 SER 358 ARG 359 ASP 360 ILE 361 GLU 362 VAL 363 GLN 364 GLY 365 PHE 366 ARG 367 ILE 368 PRO 369 LYS 370 GLY 371 THR 372 THR 373 LEU 374 ILE 375 THR 376 ASN 377 LEU 378 SER 379 SER 380 VAL 381 LEU 382 LYS 383 ASP 384 GLU 385 ALA 386 VAL 387 TRP 388 GLU 389 LYS 390 PRO 391 PHE 392 ARG 393 PHE 394 HIS 395 PRO 396 GLU 397 HIS 398 PHE 399 LEU 400 ASP 401 ALA 402 GLN 403 GLY 404 HIS 405 PHE 406 VAL 407 LYS 408 PRO 409 GLU 410 ALA 411 PHE 412 LEU 413 PRO 414 PHE 415 SER 416 ALA 417 GLY 418 ARG 419 ARG 420 ALA 421 CYS 422 LEU 423 GLY 424 GLU 425 PRO 426 LEU 427 ALA 428 ARG 429 MET 430 GLU 431 LEU 432 PHE 433 LEU 434 PHE 435 PHE 436 THR 437 SER 438 LEU 439 LEU 440 GLN 441 HIS 442 PHE 443 SER 444 PHE 445 SER 446 VAL 447 PRO 448 THR 449 GLY 450 GLN 451 PRO 452 ARG 453 PRO 454 SER 455 HIS 456 HIS 457 GLY 458 VAL 459 PHE 460 ALA 461 PHE 462 LEU 463 VAL 464 SER 465 PRO 466 SER 467 PRO 468 TYR 469 GLU 470 LEU 471 CYS 472 ALA 473 VAL 474 PRO 475 ARG 476 HIS 477 HIS 478 HIS 479 HIS stop_ _Sequence_homology_query_date . _Sequence_homology_query_revised_last_date 2015-10-28 loop_ _Database_name _Database_accession_code _Database_entry_mol_name _Sequence_query_to_submitted_percentage _Sequence_subject_length _Sequence_identity _Sequence_positive _Sequence_homology_expectation_value PDB 2F9Q "Crystal Structure Of Human Cytochrome P450 2d6" 100.00 479 100.00 100.00 0.00e+00 PDB 3QM4 "Human Cytochrome P450 (Cyp) 2d6 - Prinomastat Complex" 100.00 479 99.37 99.58 0.00e+00 PDB 3TBG "Human Cytochrome P450 2d6 With Two Thioridazines Bound In Active Site" 100.00 479 99.37 99.58 0.00e+00 PDB 3TDA "Competitive Replacement Of Thioridazine By Prinomastat In Crystals Of Cytochrome P450 2d6" 100.00 479 99.37 99.58 0.00e+00 PDB 4WNT "Human Cytochrome P450 2d6 Ajmalicine Complex" 100.00 479 99.37 99.58 0.00e+00 PDB 4WNU "Human Cytochrome P450 2d6 Quinidine Complex" 100.00 479 99.37 99.58 0.00e+00 PDB 4WNV "Human Cytochrome P450 2d6 Quinine Complex" 100.00 479 99.37 99.58 0.00e+00 PDB 4WNW "Human Cytochrome P450 2d6 Thioridazine Complex" 100.00 479 99.37 99.58 0.00e+00 PDB 4XRY "Human Cytochrome P450 2d6 Bace1 Inhibitor 5 Complex" 100.00 479 99.37 99.58 0.00e+00 PDB 4XRZ "Human Cytochrome P450 2d6 Bace1 Inhibitor 6 Complex" 100.00 479 99.37 99.58 0.00e+00 EMBL CAA30807 "cytochrome P450 db1 [Homo sapiens]" 99.16 497 97.47 98.11 0.00e+00 GB AAA36403 "cytochrome P450db1, partial [Homo sapiens]" 77.87 373 98.93 99.46 0.00e+00 GB AAA52153 "debrisoquine 4-hydroxylase [Homo sapiens]" 99.16 497 97.47 98.11 0.00e+00 GB AAA53500 "cytochrome P450 IID6 [Homo sapiens]" 99.16 497 97.26 98.11 0.00e+00 GB AAH75023 "Cytochrome P450, family 2, subfamily D, polypeptide 6 [Homo sapiens]" 99.16 497 97.26 98.11 0.00e+00 GB AAH75024 "Cytochrome P450, family 2, subfamily D, polypeptide 6 [Homo sapiens]" 99.16 497 97.26 98.11 0.00e+00 REF NP_000097 "cytochrome P450 2D6 isoform 1 [Homo sapiens]" 99.16 497 97.26 98.11 0.00e+00 REF NP_001035712 "cytochrome P450 2D6 [Pan troglodytes]" 93.95 497 98.00 99.11 0.00e+00 REF XP_005278411 "PREDICTED: cytochrome P450 2D6 isoform X6 [Homo sapiens]" 68.48 397 98.78 99.39 0.00e+00 REF XP_008975012 "PREDICTED: cytochrome P450 2D6-like, partial [Pan paniscus]" 50.31 324 98.76 98.76 8.15e-168 REF XP_011528268 "PREDICTED: cytochrome P450 2D6 isoform X1 [Homo sapiens]" 96.45 502 97.19 98.05 0.00e+00 SP P10635 "RecName: Full=Cytochrome P450 2D6; AltName: Full=CYPIID6; AltName: Full=Cholesterol 25-hydroxylase; AltName: Full=Cytochrome P4" 99.16 497 97.26 98.11 0.00e+00 SP Q2XNC8 "RecName: Full=Cytochrome P450 2D6; AltName: Full=CYPIID6; AltName: Full=Cholesterol 25-hydroxylase" 93.95 497 98.00 99.11 0.00e+00 stop_ save_ ############# # Ligands # ############# save_MPTP _Saveframe_category ligand _Mol_type non-polymer _Name_common "1-Methyl-4-phenyl-1,2,3,6-tetrahydrophyridine (MPTP)" _BMRB_code . _PDB_code . _Molecular_mass 173.25 _Mol_charge 0 _Mol_paramagnetic . _Mol_aromatic yes _Details . _Mol_thiol_state 'not present' _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 _Strain $CYP_2D6 baculovirus 10469 virus . baculovirus baculovirus Sf9 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 $CYP_2D6 'recombinant technology' . Escherichia coli . pET15b 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 _Concentration_min_value _Concentration_max_value _Isotopic_labeling $MPTP . uM 1 30 'natural abundance' $CYP_2D6 . mM 1 30 'natural abundance' 'phosphate buffer' 0.1 mM . . 'natural abundance' H2O . % . 100 'natural abundance' stop_ save_ ############################ # Computer software used # ############################ save_NMRCLUST _Saveframe_category software _Name NMRCLUST _Version . loop_ _Vendor _Address _Electronic_address '(Kelley et al., 1996)' . . stop_ loop_ _Task 'conformational clustering' stop_ _Details . save_ save_MODELLER _Saveframe_category software _Name MODELLER _Version . loop_ _Vendor _Address _Electronic_address '(Sali & Blundell, 1993)' . . stop_ loop_ _Task 'structure solution' stop_ _Details . save_ ######################### # Experimental detail # ######################### ################################## # NMR Spectrometer definitions # ################################## save_spectrometer_1 _Saveframe_category NMR_spectrometer _Manufacturer Bruker _Model AMX _Field_strength 600 _Details . save_ ############################# # NMR applied experiments # ############################# save_1H_NMR_1 _Saveframe_category NMR_applied_experiment _Experiment_name '1H NMR' _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 pH 8.0 . pH pressure 1 . atm temperature 277 . K stop_ save_