response to Gram-positive bacterium / regulation of protein catabolic process at postsynapse, modulating synaptic transmission / pituitary gland development / gamma-catenin binding / cell-cell adhesion mediated by cadherin / negative regulation of axon extension / cellular response to indole-3-methanol / flotillin complex / positive regulation of cysteine-type endopeptidase activity involved in execution phase of apoptosis / negative regulation of endoplasmic reticulum unfolded protein response ...response to Gram-positive bacterium / regulation of protein catabolic process at postsynapse, modulating synaptic transmission / pituitary gland development / gamma-catenin binding / cell-cell adhesion mediated by cadherin / negative regulation of axon extension / cellular response to indole-3-methanol / flotillin complex / positive regulation of cysteine-type endopeptidase activity involved in execution phase of apoptosis / negative regulation of endoplasmic reticulum unfolded protein response / embryonic brain development / eukaryotic 80S initiation complex / oxidized pyrimidine DNA binding / response to TNF agonist / positive regulation of base-excision repair / negative regulation of protein neddylation / Formation of definitive endoderm / calcium-dependent cell-cell adhesion via plasma membrane cell adhesion molecules / protein tyrosine kinase inhibitor activity / translation at presynapse / positive regulation of respiratory burst involved in inflammatory response / axial mesoderm development / positive regulation of intrinsic apoptotic signaling pathway in response to DNA damage / positive regulation of gastrulation / negative regulation of formation of translation preinitiation complex / nucleolus organization / ribosomal protein import into nucleus / IRE1-RACK1-PP2A complex / : / exit from mitosis / positive regulation of endodeoxyribonuclease activity / positive regulation of Golgi to plasma membrane protein transport / 90S preribosome assembly / TNFR1-mediated ceramide production / laminin receptor activity / negative regulation of DNA repair / negative regulation of RNA splicing / optic nerve development / TORC2 complex binding / Adherens junctions interactions / catenin complex / Apoptotic cleavage of cell adhesion proteins / GAIT complex / negative regulation of intrinsic apoptotic signaling pathway in response to hydrogen peroxide / oxidized purine DNA binding / supercoiled DNA binding / neural crest cell differentiation / retinal ganglion cell axon guidance / middle ear morphogenesis / NF-kappaB complex / GTPase activating protein binding / ubiquitin-like protein conjugating enzyme binding / regulation of establishment of cell polarity / negative regulation of phagocytosis / cell-cell junction assembly / positive regulation of ubiquitin-protein transferase activity / Formation of the ternary complex, and subsequently, the 43S complex / rRNA modification in the nucleus and cytosol / erythrocyte homeostasis / cytoplasmic side of rough endoplasmic reticulum membrane / adherens junction organization / A band / regulation of G1 to G0 transition / alpha-beta T cell differentiation / 顔料 / positive regulation of intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator / regulation of translation involved in cellular response to UV / protein kinase A binding / protein-DNA complex disassembly / positive regulation of DNA damage response, signal transduction by p53 class mediator resulting in transcription of p21 class mediator / Ribosomal scanning and start codon recognition / negative regulation of ubiquitin protein ligase activity / ankyrin binding / ion channel inhibitor activity / Translation initiation complex formation / apical junction complex / positive regulation of mitochondrial depolarization / response to aldosterone / G1 to G0 transition / homeostatic process / negative regulation of cell-cell adhesion / lung morphogenesis / cellular response to lithium ion / negative regulation of Wnt signaling pathway / fibroblast growth factor binding / positive regulation of T cell receptor signaling pathway / positive regulation of activated T cell proliferation / regulation of cell division / ヒドロキシル化 / iron-sulfur cluster binding / macrophage chemotaxis / BH3 domain binding / mTORC1-mediated signalling / SARS-CoV-1 modulates host translation machinery / homophilic cell adhesion via plasma membrane adhesion molecules / Peptide chain elongation / positive regulation of intrinsic apoptotic signaling pathway by p53 class mediator / Selenocysteine synthesis / monocyte chemotaxis / cysteine-type endopeptidase activator activity involved in apoptotic process 類似検索 - 分子機能
Cadherin prodomain like / Cadherin prodomain / Cadherin prodomain like / Cadherin, Y-type LIR-motif / Cadherin, Y-type LIR-motif / Catenin binding domain superfamily / カドヘリン / 40S ribosomal protein SA / 40S ribosomal protein SA, C-terminal domain / 60s Acidic ribosomal protein ...Cadherin prodomain like / Cadherin prodomain / Cadherin prodomain like / Cadherin, Y-type LIR-motif / Cadherin, Y-type LIR-motif / Catenin binding domain superfamily / カドヘリン / 40S ribosomal protein SA / 40S ribosomal protein SA, C-terminal domain / 60s Acidic ribosomal protein / Cadherin conserved site / Cadherin domain signature. / 40S ribosomal protein SA C-terminus / Cadherin repeats. / Ribosomal protein L6, N-terminal / 60S acidic ribosomal protein P0 / Ribosomal protein L6, N-terminal domain / Ribosomal protein L30e / Cadherin domain / Cadherins domain profile. / Cadherin-like / Cadherin-like superfamily / Ribosomal protein L23 / Ubiquitin-like protein FUBI / Ribosomal protein L2, archaeal-type / Ribosomal protein L28e / Ribosomal protein L41 / Ribosomal L15/L27a, N-terminal / Ribosomal protein L41 / : / 50S ribosomal protein L10, insertion domain superfamily / metallochaperone-like domain / Ribosomal L28e/Mak16 / Ribosomal L28e protein family / TRASH domain / Ribosomal protein S21e, conserved site / 60S ribosomal protein L10P, insertion domain / Insertion domain in 60S ribosomal protein L10P / Ribosomal protein S26e / Ribosomal protein S26e superfamily / Ribosomal protein S19e, conserved site / Ribosomal protein S26e / Ribosomal protein L29e / Ribosomal protein S26e signature. / Ribosomal protein S2, eukaryotic / Ribosomal L29e protein family / Ribosomal protein S21e / Ribosomal protein S21e superfamily / Ribosomal protein S21e / : / Ribosomal protein S8e subdomain, eukaryotes / Ribosomal protein S21e signature. / Ribosomal protein S12e signature. / Ribosomal protein S2, eukaryotic/archaeal / Ribosomal protein S12e / Ribosomal protein S19e / Ribosomal_S19e / Ribosomal protein S5, eukaryotic/archaeal / Ribosomal protein S8e, conserved site / : / Ribosomal protein L24e, conserved site / Ribosomal protein S4e, N-terminal, conserved site / 40S ribosomal protein S4, C-terminal domain / Ribosomal protein S19e signature. / Small (40S) ribosomal subunit Asc1/RACK1 / Ribosomal protein S19e / Ribosomal protein L22e / Ribosomal protein L22e superfamily / Ribosomal protein L23/L25, N-terminal / Ribosomal L22e protein family / 40S ribosomal protein S4 C-terminus / Ribosomal protein S4e, N-terminal / Ribosomal protein L30e, conserved site / Ribosomal protein L34e, conserved site / Ribosomal protein S23, eukaryotic/archaeal / 40S Ribosomal protein S10 / S27a-like superfamily / Ribosomal protein L23, N-terminal domain / Ribosomal protein S10, eukaryotic/archaeal / Ribosomal protein L13e, conserved site / Ribosomal protein L13e signature. / Ribosomal protein S8e / Ribosomal protein S4, KOW domain / Ribosomal protein S4e / Ribosomal protein S4e, central region / Ribosomal protein L1, conserved site / Ribosomal protein S4e, central domain superfamily / Plectin/S10, N-terminal / Plectin/S10 domain / Ribosomal protein L38e / Ribosomal protein L38e superfamily / Ribosomal L38e protein family / Ribosomal Protein L6, KOW domain / Ribosomal protein L30/YlxQ / Ribosomal protein S25 / S25 ribosomal protein / RS4NT (NUC023) domain / Ribosomal protein L1 signature. / : / Ribosomal protein L13e 類似検索 - ドメイン・相同性
Chem-MVM / リボ核酸 / RNA (> 10) / RNA (> 100) / RNA (> 1000) / FAU ubiquitin like and ribosomal protein S30 fusion / Large ribosomal subunit protein uL10 / Small ribosomal subunit protein eS17 / Small ribosomal subunit protein uS2 / E-カドヘリン ...Chem-MVM / リボ核酸 / RNA (> 10) / RNA (> 100) / RNA (> 1000) / FAU ubiquitin like and ribosomal protein S30 fusion / Large ribosomal subunit protein uL10 / Small ribosomal subunit protein eS17 / Small ribosomal subunit protein uS2 / E-カドヘリン / Small ribosomal subunit protein uS5 / Large ribosomal subunit protein eL33 / Large ribosomal subunit protein uL30 / Large ribosomal subunit protein uL22 / Small ribosomal subunit protein eS4, Y isoform 1 / Small ribosomal subunit protein uS3 / Small ribosomal subunit protein eS12 / Large ribosomal subunit protein eL13 / Large ribosomal subunit protein uL16 / Large ribosomal subunit protein uL11 / Large ribosomal subunit protein uL6 / Large ribosomal subunit protein eL22 / Large ribosomal subunit protein uL4 / Small ribosomal subunit protein eS19 / Large ribosomal subunit protein uL3 / Large ribosomal subunit protein uL13 / Small ribosomal subunit protein eS27 / Large ribosomal subunit protein uL29 / Large ribosomal subunit protein uL15 / Large ribosomal subunit protein uL18 / Large ribosomal subunit protein eL21 / Large ribosomal subunit protein eL28 / Small ribosomal subunit protein uS4 / Small ribosomal subunit protein uS7 / Small ribosomal subunit protein eS10 / Large ribosomal subunit protein eL29 / Large ribosomal subunit protein eL34 / Large ribosomal subunit protein eL14 / Small ribosomal subunit protein uS10 / Small ribosomal subunit protein eS1 / Large ribosomal subunit protein uL24 / Large ribosomal subunit protein eL15 / Large ribosomal subunit protein eL27 / Large ribosomal subunit protein eL43 / Large ribosomal subunit protein eL37 / Small ribosomal subunit protein eS7 / Small ribosomal subunit protein eS8 / Small ribosomal subunit protein uS8 / Small ribosomal subunit protein uS9 / Small ribosomal subunit protein uS11 / Small ribosomal subunit protein uS12 / Small ribosomal subunit protein uS13 / Small ribosomal subunit protein uS14 / Small ribosomal subunit protein uS15 / Small ribosomal subunit protein uS17 / Large ribosomal subunit protein eL8 / Large ribosomal subunit protein uL23 / Small ribosomal subunit protein eS6 / Large ribosomal subunit protein uL14 / Small ribosomal subunit protein uS19 / Small ribosomal subunit protein eS24 / Small ribosomal subunit protein eS25 / Small ribosomal subunit protein eS26 / Small ribosomal subunit protein eS28 / Ubiquitin-like FUBI-ribosomal protein eS30 fusion protein / Large ribosomal subunit protein eL30 / Large ribosomal subunit protein eL39 / Large ribosomal subunit protein eL31 / Large ribosomal subunit protein uL1 / Large ribosomal subunit protein eL32 / Large ribosomal subunit protein uL5 / Large ribosomal subunit protein uL2 / Small ribosomal subunit protein eS32 / Ubiquitin-ribosomal protein eS31 fusion protein / Ubiquitin-ribosomal protein eL40 fusion protein / Large ribosomal subunit protein eL38 / Small ribosomal subunit protein eS21 / Small ribosomal subunit protein RACK1 / Large ribosomal subunit protein eL24 / Large ribosomal subunit protein eL42 / Large ribosomal subunit protein eL19 / Large ribosomal subunit protein eL20 / Large ribosomal subunit protein eL6 / Large ribosomal subunit protein eL18 / Large ribosomal subunit protein uL14 / Large ribosomal subunit protein eL36 類似検索 - 構成要素
National Institutes of Health/National Human Genome Research Institute (NIH/NHGRI)
R01-GM065050
米国
引用
ジャーナル: Nat Struct Mol Biol / 年: 2019 タイトル: Structural basis for selective stalling of human ribosome nascent chain complexes by a drug-like molecule. 著者: Wenfei Li / Fred R Ward / Kim F McClure / Stacey Tsai-Lan Chang / Elizabeth Montabana / Spiros Liras / Robert G Dullea / Jamie H D Cate / 要旨: The drug-like molecule PF-06446846 (PF846) binds the human ribosome and selectively blocks the translation of a small number of proteins by an unknown mechanism. In structures of PF846-stalled human ...The drug-like molecule PF-06446846 (PF846) binds the human ribosome and selectively blocks the translation of a small number of proteins by an unknown mechanism. In structures of PF846-stalled human ribosome nascent chain complexes, PF846 binds in the ribosome exit tunnel in a eukaryotic-specific pocket formed by 28S ribosomal RNA, and alters the path of the nascent polypeptide chain. PF846 arrests the translating ribosome in the rotated state of translocation, in which the peptidyl-transfer RNA 3'-CCA end is improperly docked in the peptidyl transferase center. Selections of messenger RNAs from mRNA libraries using translation extracts reveal that PF846 can stall translation elongation, arrest termination or even enhance translation, depending on nascent chain sequence context. These results illuminate how a small molecule selectively targets translation by the human ribosome, and provides a foundation for developing small molecules that modulate the production of proteins of therapeutic interest.
60S ribosomal protein ... , 44種, 44分子 AAABACADAEAFAGAHAIAJALAMANAOAPAQARASATAUAVAWAXAYAZAaAbAcAdAe...
#1: タンパク質
60SribosomalproteinL8 / / Large ribosomal subunit protein uL2
分子量: 28088.863 Da / 分子数: 1 / 由来タイプ: 天然 / 由来: (天然) Homo sapiens (ヒト) / 参照: UniProt: P62917
#3: タンパク質
60SribosomalproteinL3 / / HIV-1 TAR RNA-binding protein B / TARBP-B / Large ribosomal subunit protein uL3
分子量: 45222.949 Da / 分子数: 1 / 由来タイプ: 天然 / 由来: (天然) Homo sapiens (ヒト) / 参照: UniProt: P39023
#5: タンパク質
60SribosomalproteinL4 / / 60S ribosomal protein L1 / Large ribosomal subunit protein uL4
分子量: 41171.547 Da / 分子数: 1 / 由来タイプ: 天然 / 由来: (天然) Homo sapiens (ヒト) / 参照: UniProt: P36578
#9: タンパク質
60SribosomalproteinL5 / / Large ribosomal subunit protein uL18
分子量: 34091.371 Da / 分子数: 1 / 由来タイプ: 天然 / 由来: (天然) Homo sapiens (ヒト) / 参照: UniProt: P46777
#10: タンパク質
60SribosomalproteinL6 / / Large ribosomal subunit protein eL6 / Neoplasm-related protein C140 / Tax-responsive enhancer ...Large ribosomal subunit protein eL6 / Neoplasm-related protein C140 / Tax-responsive enhancer element-binding protein 107 / TaxREB107
分子量: 22262.428 Da / 分子数: 1 / 由来タイプ: 天然 / 由来: (天然) Homo sapiens (ヒト) / 参照: UniProt: Q02878
#11: タンパク質
60SribosomalproteinL7 / / Large ribosomal subunit protein uL30
分子量: 27733.146 Da / 分子数: 1 / 由来タイプ: 天然 / 由来: (天然) Homo sapiens (ヒト) / 参照: UniProt: P18124
#12: タンパク質
60SribosomalproteinL7a / / Large ribosomal subunit protein eL8 / PLA-X polypeptide / Surfeit locus protein 3
分子量: 26724.568 Da / 分子数: 1 / 由来タイプ: 天然 / 由来: (天然) Homo sapiens (ヒト) / 参照: UniProt: P62424
#13: タンパク質
60SribosomalproteinL9 / / Large ribosomal subunit protein uL6
分子量: 21770.355 Da / 分子数: 1 / 由来タイプ: 天然 / 由来: (天然) Homo sapiens (ヒト) / 参照: UniProt: P32969
#14: タンパク質
60SribosomalproteinL10 / / Laminin receptor homolog / Large ribosomal subunit protein uL16 / Protein QM / Ribosomal protein ...Laminin receptor homolog / Large ribosomal subunit protein uL16 / Protein QM / Ribosomal protein L10 / Tumor suppressor QM
分子量: 24381.760 Da / 分子数: 1 / 由来タイプ: 天然 / 由来: (天然) Homo sapiens (ヒト) / 参照: UniProt: P27635
#15: タンパク質
60SribosomalproteinL11 / / CLL-associated antigen KW-12 / Large ribosomal subunit protein uL5
分子量: 19270.318 Da / 分子数: 1 / 由来タイプ: 天然 / 由来: (天然) Homo sapiens (ヒト) / 参照: UniProt: P62913
#17: タンパク質
60SribosomalproteinL13 / / Breast basic conserved protein 1 / Large ribosomal subunit protein eL13
分子量: 23574.697 Da / 分子数: 1 / 由来タイプ: 天然 / 由来: (天然) Homo sapiens (ヒト) / 参照: UniProt: P26373
#18: タンパク質
60SribosomalproteinL14 / / CAG-ISL 7 / Large ribosomal subunit protein eL14
分子量: 16220.309 Da / 分子数: 1 / 由来タイプ: 天然 / 由来: (天然) Homo sapiens (ヒト) / 参照: UniProt: P50914
#19: タンパク質
60SribosomalproteinL15 / / Large ribosomal subunit protein eL15
分子量: 24076.088 Da / 分子数: 1 / 由来タイプ: 天然 / 由来: (天然) Homo sapiens (ヒト) / 参照: UniProt: P61313
#20: タンパク質
60SribosomalproteinL13a / / 23 kDa highly basic protein / Large ribosomal subunit protein uL13
分子量: 22820.395 Da / 分子数: 1 / 由来タイプ: 天然 / 由来: (天然) Homo sapiens (ヒト) / 参照: UniProt: P40429
#21: タンパク質
60SribosomalproteinL17 / / 60S ribosomal protein L23 / Large ribosomal subunit protein uL22 / PD-1
分子量: 17757.627 Da / 分子数: 1 / 由来タイプ: 天然 / 由来: (天然) Homo sapiens (ヒト) / 参照: UniProt: P18621
#22: タンパク質
60SribosomalproteinL18 / / Large ribosomal subunit protein eL18
分子量: 21556.482 Da / 分子数: 1 / 由来タイプ: 天然 / 由来: (天然) Homo sapiens (ヒト) / 参照: UniProt: Q07020
#23: タンパク質
60SribosomalproteinL19 / / Large ribosomal subunit protein eL19
分子量: 21742.146 Da / 分子数: 1 / 由来タイプ: 天然 / 由来: (天然) Homo sapiens (ヒト) / 参照: UniProt: P84098
#24: タンパク質
60SribosomalproteinL18a / / Large ribosomal subunit protein eL20
分子量: 20661.340 Da / 分子数: 1 / 由来タイプ: 天然 / 由来: (天然) Homo sapiens (ヒト) / 参照: UniProt: Q02543
#25: タンパク質
60SribosomalproteinL21 / / Large ribosomal subunit protein eL21
分子量: 18276.518 Da / 分子数: 1 / 由来タイプ: 天然 / 由来: (天然) Homo sapiens (ヒト) / 参照: UniProt: P46778
#26: タンパク質
60SribosomalproteinL22 / / EBER-associated protein / EAP / Epstein-Barr virus small RNA-associated protein / Heparin-binding ...EBER-associated protein / EAP / Epstein-Barr virus small RNA-associated protein / Heparin-binding protein HBp15 / Large ribosomal subunit protein eL22
分子量: 11481.248 Da / 分子数: 1 / 由来タイプ: 天然 / 由来: (天然) Homo sapiens (ヒト) / 参照: UniProt: P35268
40SribosomalproteinS27a / / Ubiquitin carboxyl extension protein 80
分子量: 8645.277 Da / 分子数: 1 / 由来タイプ: 天然 / 由来: (天然) Homo sapiens (ヒト) / 参照: UniProt: P62979
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RNA鎖 , 6種, 6分子 A3A4A2B1BvBx
#7: RNA鎖
5.8SribosomalRNA / 5.8SリボソームRNA
分子量: 50449.812 Da / 分子数: 1 / 由来タイプ: 天然 / 由来: (天然) Homo sapiens (ヒト)
#8: RNA鎖
5SribosomalRNA / 5SリボソームRNA
分子量: 38385.750 Da / 分子数: 1 / 由来タイプ: 天然 / 由来: (天然) Homo sapiens (ヒト)
#51: RNA鎖
28SribosomalRNA / 28SリボソームRNA
分子量: 1170164.875 Da / 分子数: 1 / 由来タイプ: 天然 / 由来: (天然) Homo sapiens (ヒト)
#52: RNA鎖
18SribosomalRNA /
分子量: 551108.188 Da / 分子数: 1 / 由来タイプ: 天然 / 由来: (天然) Homo sapiens (ヒト)
#83: RNA鎖
tRNA / 転移RNA
分子量: 24485.539 Da / 分子数: 1 / 由来タイプ: 天然 / 由来: (天然) Homo sapiens (ヒト)
#84: RNA鎖
mRNA / 伝令RNA
分子量: 4853.695 Da / 分子数: 1 / 由来タイプ: 天然 / 由来: (天然) Homo sapiens (ヒト)
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タンパク質 , 2種, 2分子 AKBg
#16: タンパク質
60SacidicribosomalproteinP0 / / 60S ribosomal protein L10E / Large ribosomal subunit protein uL10
分子量: 12505.798 Da / 分子数: 1 / 由来タイプ: 天然 / 由来: (天然) Homo sapiens (ヒト) / 参照: UniProt: P05388
#82: タンパク質
ReceptorofactivatedproteinCkinase1 / Cell proliferation-inducing gene 21 protein / Guanine nucleotide-binding protein subunit beta-2- ...Cell proliferation-inducing gene 21 protein / Guanine nucleotide-binding protein subunit beta-2-like 1 / Guanine nucleotide-binding protein subunit beta-like protein 12.3 / Human lung cancer oncogene 7 protein / HLC-7 / Receptor for activated C kinase / Small ribosomal subunit protein RACK1
分子量: 34726.164 Da / 分子数: 1 / 由来タイプ: 天然 / 由来: (天然) Homo sapiens (ヒト) / 参照: UniProt: P63244