IntAct European Bioinformatics Institute IntAct intact http://www.ebi.ac.uk/ http://www.ebi.ac.uk/intact/query/${ac} EBI-[0-9]+|IA:[0-9]+ INTerAction database (IntAct) provides an open source database and toolkit for the storage, presentation and analysis of molecular interactions. http://www.ebi.ac.uk/intact European Bioinformatics Institute; Wellcome Trust Genome Campus; Hinxton, Cambridge; CB10 1SD; United Kingdom http://www.ebi.ac.uk/intact/ Binding of a cyano- and fluoro-containing drug bicalutamide to cytochrome P450 46A1: unusual features and spectral response. Binding of a cyano- and fluoro-containing drug bicalutamide to cytochrome P450 46A1: unusual features and spectral response. The Journal of biological chemistry 2013 imex curation Mast N., Zheng W., Stout CD., Pikuleva IA. dave@scripps.edu,iap8@case.edu 30-Aug-2019: Contacted by IntAct-Help. Only protein-protein interactions imex curation in vitro In vitro uv-vis ultraviolet-visible spectroscopy uv-vis predetermined predetermined participant predetermined Mast N., Zheng W., Stout CD., Pikuleva IA. dave@scripps.edu,iap8@case.edu Accepted 2019-AUG-23 AT 08:26 BST AT 08:26 BST by MGT The Journal of biological chemistry 2013 Only protein-protein interactions imex curation imex curation Binding of a cyano- and fluoro-containing drug bicalutamide to cytochrome P450 46A1: unusual features and spectral response. Binding of a cyano- and fluoro-containing drug bicalutamide to cytochrome P450 46A1: unusual features and spectral response. The Journal of biological chemistry 2013 imex curation Mast N., Zheng W., Stout CD., Pikuleva IA. dave@scripps.edu,iap8@case.edu 30-Aug-2019: Contacted by IntAct-Help. Only protein-protein interactions imex curation in vitro In vitro x-ray diffraction x-ray crystallography X-ray X-ray x-ray diffraction predetermined predetermined participant predetermined Mast N., Zheng W., Stout CD., Pikuleva IA. dave@scripps.edu,iap8@case.edu Accepted 2019-AUG-23 AT 08:26 BST AT 08:26 BST by MGT The Journal of biological chemistry 2013 Only protein-protein interactions imex curation imex curation removed the 'link' between the participants; interaction type changed; Kd values (for figure 8) checked and corrected wherever needed; The Biological roles (enzyme/target) corrected. I entered a Kd for figure 1B for you, and altered the Kd for the RAC form of P450, as they give two values - one from the image (1.6 as you entered) and the text elsewhere states 1.2 - so I averaged them. Let me know if it should be 1.6! - Thank you! (24s)-24-hydroxycholesterol (24S)-24-hydroxycholesterol (24S)-24-Hydroxycholesterol (24S)-hydroxycholesterol 24-Hydroxycholesterol 24S-hydroxy-cholesterol Cerebrosterol cholest-5-en-3beta,24S-diol Cholest-5-ene-3,24-diol (24S)-cholest-5-ene-3beta,24-diol small molecule small molecule chemical synthesis Chemical synthesis (Chemical synthesis) cp46a_human Cholesterol 24-hydroxylase CYP46A1 CYP46 Cytochrome P450 46A1 Cholesterol 24-monooxygenase Cholesterol 24S-hydroxylase protein protein human Homo sapiens Human MSPGLLLLGSAVLLAFGLCCTFVHRARSRYEHIPGPPRPSFLLGHLPCFWKKDEVGGRVLQDVFLDWAKKYGPVVRVNVFHKTSVIVTSPESVKKFLMSTKYNKDSKMYRALQTVFGERLFGQGLVSECNYERWHKQRRVIDLAFSRSSLVSLMETFNEKAEQLVEILEAKADGQTPVSMQDMLTYTAMDILAKAAFGMETSMLLGAQKPLSQAVKLMLEGITASRNTLAKFLPGKRKQLREVRESIRFLRQVGRDWVQRRREALKRGEEVPADILTQILKAEEGAQDDEGLLDNFVTFFIAGHETSANHLAFTVMELSRQPEIVARLQAEVDEVIGSKRYLDFEDLGRLQYLSQVLKESLRLYPPAWGTFRLLEEETLIDGVRVPGNTPLLFSTYVMGRMDTYFEDPLTFNPDRFGPGAPKPRFTYFPFSLGHRSCIGQQFAQMEVKVVMAKLLQRLEFRLVPGQRFGLQEQATLKPLDPVLCTLRPRGWQPAPPPPPC AB9307749D9E5FDA (s)-bicalutamide (S)-bicalutamide (+)-bicalutamide (S)-Casodex (2S)-N-[4-cyano-3-(trifluoromethyl)phenyl]-3-[(4-fluorophenyl)sulfonyl]-2-hydroxy-2-methylpropanamide small molecule small molecule chemical synthesis Chemical synthesis (Chemical synthesis) heme b Heme b small molecule small molecule chemical synthesis Chemical synthesis (Chemical synthesis) (r)-bicalutamide (R)-bicalutamide (-)-bicalutamide (R)-(-)bicalutamide (R)-Casodex (2R)-N-[4-cyano-3-(trifluoromethyl)phenyl]-3-[(4-fluorophenyl)sulfonyl]-2-hydroxy-2-methylpropanamide small molecule small molecule chemical synthesis Chemical synthesis (Chemical synthesis) bicalutamide Bicalutamide, an androgen antagonist small molecule small molecule chemical synthesis Chemical synthesis (Chemical synthesis) bicalutamide-cyp46a1-1 2 4 unspecified role unspecified role neutral component neutral component purified purified region sufficient to bind sufficient binding region sufficient to bind certain certain sequence position certain certain certain sequence position certain C-terminus his tag his tag Hexa-His-tag 6-His-tag Histidine-tag Hexa-His-tag Histidine-tag 6-His-tag c-term range C-terminal range c-term range c-term range C-terminal range c-term range ecoli Escherichia coli (strain K12) 5 unspecified role unspecified role neutral component neutral component purified purified chemical synthesis Chemical synthesis (Chemical synthesis) 7 unspecified role unspecified role neutral component neutral component purified purified chemical synthesis Chemical synthesis (Chemical synthesis) 6 cofactor cofactor coenzyme neutral component neutral component purified purified chemical synthesis Chemical synthesis (Chemical synthesis) physical association physical association TABLE 1, FIG. 3 2.1Å Rwork: 0.208 Rfree: 0.253 bicalutamide-cyp46a1-2 1 8 unspecified role unspecified role neutral component neutral component purified purified chemical synthesis Chemical synthesis (Chemical synthesis) 4 unspecified role unspecified role neutral component neutral component purified purified Q9Y6A2:p.Arg226Met mutation disrupting strength mutation disrupting interaction strength mutation disrupting strength certain certain sequence position certain certain certain sequence position certain R M Tue Jun 30 17:22:25 BST 2020 This feature has been corrected as a result of our quality control procedures. The original label was 'p.Arg226Met' Q9Y6A2:p.His81Ala mutation with no effect mutation with no effect mutation with no effect mutation not affecting interaction certain certain sequence position certain certain certain sequence position certain H A Tue Jun 30 16:09:57 BST 2020 This feature has been corrected as a result of our quality control procedures. The original label was 'p.His81Ala' Q9Y6A2:p.Lys82Glu mutation decreasing strength mutation decreasing interaction strength mutation decreasing strength certain certain sequence position certain certain certain sequence position certain K E Tue Jun 30 16:38:55 BST 2020 This feature has been corrected as a result of our quality control procedures. The original label was 'p.Lys82Glu' Q9Y6A2:p.Lys82Met mutation increasing strength mutation increasing interaction strength mutation increasing strength certain certain sequence position certain certain certain sequence position certain K M Tue Jun 30 19:35:02 BST 2020 This feature has been corrected as a result of our quality control procedures. The original label was 'p.Lys82Met' Q9Y6A2:p.Arg110Leu mutation decreasing strength mutation decreasing interaction strength mutation decreasing strength certain certain sequence position certain certain certain sequence position certain R L Tue Jun 30 18:50:23 BST 2020 This feature has been corrected as a result of our quality control procedures. The original label was 'p.Arg110Leu' Q9Y6A2:p.Arg226Glu mutation increasing strength mutation increasing interaction strength mutation increasing strength certain certain sequence position certain certain certain sequence position certain R E Tue Jun 30 16:24:30 BST 2020 This feature has been corrected as a result of our quality control procedures. The original label was 'p.Arg226Glu' Q9Y6A2:p.Thr306Ala mutation decreasing strength mutation decreasing interaction strength mutation decreasing strength certain certain sequence position certain certain certain sequence position certain T A Tue Jun 30 17:54:04 BST 2020 This feature has been corrected as a result of our quality control procedures. The original label was 'p.Thr306Ala' Q9Y6A2:p.Trp368Phe mutation increasing strength mutation increasing interaction strength mutation increasing strength certain certain sequence position certain certain certain sequence position certain W F Tue Jun 30 18:58:01 BST 2020 This feature has been corrected as a result of our quality control procedures. The original label was 'p.Trp368Phe' Q9Y6A2:p.Ala474Val mutation decreasing strength mutation decreasing interaction strength mutation decreasing strength certain certain sequence position certain certain certain sequence position certain A V Tue Jun 30 17:30:15 BST 2020 This feature has been corrected as a result of our quality control procedures. The original label was 'p.Ala474Val' ecoli Escherichia coli (strain K12) direct interaction direct interaction FIGURES 1A, 1C, 8, 9 Changes elicited by racBIC in CYP46A1-imidazole adduct were identical to those in substrate-free CYP46A1. (s)_bicalutamide-cyp46a1-1 1 5 unspecified role unspecified role neutral component neutral component purified purified chemical synthesis Chemical synthesis (Chemical synthesis) 4 unspecified role unspecified role neutral component neutral component purified purified Q9Y6A2:p.Lys82Glu mutation increasing strength mutation increasing interaction strength mutation increasing strength certain certain sequence position certain certain certain sequence position certain K E Tue Jun 30 17:52:08 BST 2020 This feature has been corrected as a result of our quality control procedures. The original label was 'p.Lys82Glu' Q9Y6A2:p.His81Ala mutation increasing strength mutation increasing interaction strength mutation increasing strength certain certain sequence position certain certain certain sequence position certain H A Tue Jun 30 17:37:20 BST 2020 This feature has been corrected as a result of our quality control procedures. The original label was 'p.His81Ala' Q9Y6A2:p.Lys82Met mutation increasing strength mutation increasing interaction strength mutation increasing strength certain certain sequence position certain certain certain sequence position certain K M Tue Jun 30 18:39:52 BST 2020 This feature has been corrected as a result of our quality control procedures. The original label was 'p.Lys82Met' Q9Y6A2:p.Arg110Leu mutation increasing strength mutation increasing interaction strength mutation increasing strength certain certain sequence position certain certain certain sequence position certain R L Tue Jun 30 17:43:32 BST 2020 This feature has been corrected as a result of our quality control procedures. The original label was 'p.Arg110Leu' Q9Y6A2:p.Arg226Glu mutation increasing strength mutation increasing interaction strength mutation increasing strength certain certain sequence position certain certain certain sequence position certain R E Tue Jun 30 16:41:13 BST 2020 This feature has been corrected as a result of our quality control procedures. The original label was 'p.Arg226Glu' Q9Y6A2:p.Arg226Met mutation increasing strength mutation increasing interaction strength mutation increasing strength certain certain sequence position certain certain certain sequence position certain R M Tue Jun 30 18:19:34 BST 2020 This feature has been corrected as a result of our quality control procedures. The original label was 'p.Arg226Met' Q9Y6A2:p.Thr306Ala mutation decreasing strength mutation decreasing interaction strength mutation decreasing strength certain certain sequence position certain certain certain sequence position certain T A Tue Jun 30 20:02:42 BST 2020 This feature has been corrected as a result of our quality control procedures. The original label was 'p.Thr306Ala' Q9Y6A2:p.Trp368Phe mutation increasing strength mutation increasing interaction strength mutation increasing strength certain certain sequence position certain certain certain sequence position certain W F Tue Jun 30 18:59:29 BST 2020 This feature has been corrected as a result of our quality control procedures. The original label was 'p.Trp368Phe' Q9Y6A2:p.Ala474Val mutation increasing strength mutation increasing interaction strength mutation increasing strength certain certain sequence position certain certain certain sequence position certain A V Tue Jun 30 20:02:11 BST 2020 This feature has been corrected as a result of our quality control procedures. The original label was 'p.Ala474Val' ecoli Escherichia coli (strain K12) direct interaction direct interaction FIGURES 1D, 8, 9 (r)_bicalutamide-cyp46a1-1 1 7 unspecified role unspecified role neutral component neutral component purified purified chemical synthesis Chemical synthesis (Chemical synthesis) 4 unspecified role unspecified role neutral component neutral component purified purified Q9Y6A2:p.Arg226Glu mutation increasing strength mutation increasing interaction strength mutation increasing strength certain certain sequence position certain certain certain sequence position certain R E Tue Jun 30 15:40:52 BST 2020 This feature has been corrected as a result of our quality control procedures. The original label was 'p.Arg226Glu' Q9Y6A2:p.Arg226Met mutation decreasing strength mutation decreasing interaction strength mutation decreasing strength certain certain sequence position certain certain certain sequence position certain R M Tue Jun 30 17:39:14 BST 2020 This feature has been corrected as a result of our quality control procedures. The original label was 'p.Arg226Met' Q9Y6A2:p.Thr306Ala mutation disrupting strength mutation disrupting interaction strength mutation disrupting strength certain certain sequence position certain certain certain sequence position certain T A Tue Jun 30 15:50:13 BST 2020 This feature has been corrected as a result of our quality control procedures. The original label was 'p.Thr306Ala' Q9Y6A2:p.Trp368Phe mutation increasing strength mutation increasing interaction strength mutation increasing strength certain certain sequence position certain certain certain sequence position certain W F Tue Jun 30 19:50:26 BST 2020 This feature has been corrected as a result of our quality control procedures. The original label was 'p.Trp368Phe' Q9Y6A2:p.Ala474Val mutation decreasing strength mutation decreasing interaction strength mutation decreasing strength certain certain sequence position certain certain certain sequence position certain A V Tue Jun 30 17:33:00 BST 2020 This feature has been corrected as a result of our quality control procedures. The original label was 'p.Ala474Val' Q9Y6A2:p.Lys82Glu mutation decreasing strength mutation decreasing interaction strength mutation decreasing strength certain certain sequence position certain certain certain sequence position certain K E Tue Jun 30 17:57:31 BST 2020 This feature has been corrected as a result of our quality control procedures. The original label was 'p.Lys82Glu' Q9Y6A2:p.His81Ala mutation increasing strength mutation increasing interaction strength mutation increasing strength certain certain sequence position certain certain certain sequence position certain H A Tue Jun 30 17:20:30 BST 2020 This feature has been corrected as a result of our quality control procedures. The original label was 'p.His81Ala' Q9Y6A2:p.Lys82Met mutation decreasing strength mutation decreasing interaction strength mutation decreasing strength certain certain sequence position certain certain certain sequence position certain K M Tue Jun 30 18:05:10 BST 2020 This feature has been corrected as a result of our quality control procedures. The original label was 'p.Lys82Met' Q9Y6A2:p.Arg110Leu mutation increasing strength mutation increasing interaction strength mutation increasing strength certain certain sequence position certain certain certain sequence position certain R L Tue Jun 30 19:04:30 BST 2020 This feature has been corrected as a result of our quality control procedures. The original label was 'p.Arg110Leu' ecoli Escherichia coli (strain K12) direct interaction direct interaction FIGURES 1E, 8, 9 (24s)_24_hydroxycholesterol-cyp46a1-1 1 4 unspecified role unspecified role neutral component neutral component purified purified ecoli Escherichia coli (strain K12) 3 unspecified role unspecified role neutral component neutral component purified purified chemical synthesis Chemical synthesis (Chemical synthesis) enzymatic reaction enzymatic reaction Biochemical reaction Biochemical reaction FIGURE 1B