登録情報 データベース : PDB / ID : 7djt 構造の表示 ダウンロードとリンクタイトル Human SARM1 inhibitory state bounded with inhibitor dHNN 要素NAD(+) hydrolase SARM1 詳細 キーワード HYDROLASE / NAD(+) hydrolase機能・相同性 機能・相同性情報分子機能 ドメイン・相同性 構成要素
negative regulation of MyD88-independent toll-like receptor signaling pathway / MyD88-independent TLR4 cascade / Toll Like Receptor 3 (TLR3) Cascade / NADP+ nucleosidase activity / NAD catabolic process / ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase / NAD+ nucleosidase activity / protein localization to mitochondrion / NAD+ nucleotidase, cyclic ADP-ribose generating / nervous system process ... negative regulation of MyD88-independent toll-like receptor signaling pathway / MyD88-independent TLR4 cascade / Toll Like Receptor 3 (TLR3) Cascade / NADP+ nucleosidase activity / NAD catabolic process / ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase / NAD+ nucleosidase activity / protein localization to mitochondrion / NAD+ nucleotidase, cyclic ADP-ribose generating / nervous system process / 加水分解酵素; 糖加水分解酵素; N-グリコシル化合物加水分解酵素 / regulation of dendrite morphogenesis / response to axon injury / regulation of neuron apoptotic process / response to glucose / signaling adaptor activity / TRAF6-mediated induction of TAK1 complex within TLR4 complex / Activation of IRF3, IRF7 mediated by TBK1, IKKε (IKBKE) / IKK complex recruitment mediated by RIP1 / nervous system development / microtubule / mitochondrial outer membrane / cell differentiation / axon / innate immune response / synapse / dendrite / cell surface / signal transduction / protein-containing complex / mitochondrion / identical protein binding / cytoplasm / cytosol 類似検索 - 分子機能 Sterile alpha and TIR motif-containing protein 1 / TIR domain / Toll - interleukin 1 - resistance / TIR domain profile. / Toll/interleukin-1 receptor homology (TIR) domain / Toll/interleukin-1 receptor homology (TIR) domain superfamily / SAM domain (Sterile alpha motif) / SAM domain profile. / Sterile alpha motif. / Sterile alpha motif domain ... Sterile alpha and TIR motif-containing protein 1 / TIR domain / Toll - interleukin 1 - resistance / TIR domain profile. / Toll/interleukin-1 receptor homology (TIR) domain / Toll/interleukin-1 receptor homology (TIR) domain superfamily / SAM domain (Sterile alpha motif) / SAM domain profile. / Sterile alpha motif. / Sterile alpha motif domain / Sterile alpha motif/pointed domain superfamily / Armadillo-like helical / Armadillo-type fold 類似検索 - ドメイン・相同性生物種 Homo sapiens (ヒト)手法 電子顕微鏡法 / 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度 : 2.8 Å 詳細データ登録者 Cai, Y. / Zhang, H. 引用ジャーナル : Elife / 年 : 2021タイトル : Permeant fluorescent probes visualize the activation of SARM1 and uncover an anti-neurodegenerative drug candidate.著者 : Wan Hua Li / Ke Huang / Yang Cai / Qian Wen Wang / Wen Jie Zhu / Yun Nan Hou / Sujing Wang / Sheng Cao / Zhi Ying Zhao / Xu Jie Xie / Yang Du / Chi-Sing Lee / Hon Cheung Lee / Hongmin Zhang / Yong Juan Zhao / 要旨 : SARM1 regulates axonal degeneration through its NAD-metabolizing activity and is a drug target for neurodegenerative disorders. We designed and synthesized fluorescent conjugates of styryl derivative ... SARM1 regulates axonal degeneration through its NAD-metabolizing activity and is a drug target for neurodegenerative disorders. We designed and synthesized fluorescent conjugates of styryl derivative with pyridine to serve as substrates of SARM1, which exhibited large red shifts after conversion. With the conjugates, SARM1 activation was visualized in live cells following elevation of endogenous NMN or treatment with a cell-permeant NMN-analog. In neurons, imaging documented mouse SARM1 activation preceded vincristine-induced axonal degeneration by hours. Library screening identified a derivative of nisoldipine (NSDP) as a covalent inhibitor of SARM1 that reacted with the cysteines, especially Cys311 in its ARM domain and blocked its NMN-activation, protecting axons from degeneration. The Cryo-EM structure showed that SARM1 was locked into an inactive conformation by the inhibitor, uncovering a potential neuroprotective mechanism of dihydropyridines. 履歴 登録 2020年11月21日 登録サイト : PDBJ / 処理サイト : PDBJ改定 1.0 2021年5月19日 Provider : repository / タイプ : Initial release改定 2.0 2023年4月5日 Group : Advisory / Atomic model ... Advisory / Atomic model / Author supporting evidence / Data collection / Database references / Derived calculations / Experimental preparation / Non-polymer description / Polymer sequence / Source and taxonomy / Structure summary カテゴリ : atom_site / chem_comp ... atom_site / chem_comp / database_2 / em_image_recording / em_specimen / em_vitrification / entity / entity_poly / entity_poly_seq / entity_src_gen / pdbx_entity_instance_feature / pdbx_entity_nonpoly / pdbx_nonpoly_scheme / pdbx_poly_seq_scheme / pdbx_struct_assembly_gen / pdbx_struct_mod_residue / pdbx_validate_close_contact / pdbx_validate_main_chain_plane / pdbx_validate_rmsd_angle / struct_asym / struct_conn Item : _atom_site.B_iso_or_equiv / _atom_site.Cartn_x ... _atom_site.B_iso_or_equiv / _atom_site.Cartn_x / _atom_site.Cartn_y / _atom_site.Cartn_z / _atom_site.auth_asym_id / _atom_site.auth_atom_id / _atom_site.auth_comp_id / _atom_site.auth_seq_id / _atom_site.group_PDB / _atom_site.label_asym_id / _atom_site.label_atom_id / _atom_site.label_comp_id / _atom_site.label_entity_id / _atom_site.label_seq_id / _atom_site.type_symbol / _chem_comp.formula / _chem_comp.formula_weight / _chem_comp.id / _chem_comp.mon_nstd_flag / _chem_comp.name / _chem_comp.type / _database_2.pdbx_DOI / _database_2.pdbx_database_accession / _em_image_recording.detector_mode / _em_specimen.concentration / _em_vitrification.chamber_temperature / _em_vitrification.details / _em_vitrification.humidity / _em_vitrification.instrument / _entity_poly.nstd_monomer / _entity_poly.pdbx_seq_one_letter_code / _entity_poly_seq.mon_id / _entity_src_gen.gene_src_common_name / _pdbx_poly_seq_scheme.auth_mon_id / _pdbx_poly_seq_scheme.mon_id / _pdbx_poly_seq_scheme.pdb_mon_id / _pdbx_struct_assembly_gen.asym_id_list / _struct_conn.pdbx_dist_value / _struct_conn.pdbx_leaving_atom_flag / _struct_conn.ptnr1_auth_comp_id / _struct_conn.ptnr1_auth_seq_id / _struct_conn.ptnr1_label_atom_id / _struct_conn.ptnr1_label_comp_id / _struct_conn.ptnr1_label_seq_id / _struct_conn.ptnr2_auth_comp_id / _struct_conn.ptnr2_auth_seq_id / _struct_conn.ptnr2_label_asym_id / _struct_conn.ptnr2_label_atom_id / _struct_conn.ptnr2_label_comp_id / _struct_conn.ptnr2_label_seq_id 改定 3.0 2023年11月15日 Group : Atomic model / Data collection / Non-polymer descriptionカテゴリ : atom_site / chem_comp ... atom_site / chem_comp / chem_comp_atom / chem_comp_bond / pdbx_validate_main_chain_plane / pdbx_validate_rmsd_angle Item : _atom_site.auth_atom_id / _atom_site.label_atom_id / _chem_comp.formula