- EMDB-7024: Cryo-EM structure of the small subunit of Leishmania ribosome bou... -
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基本情報
登録情報
データベース: EMDB / ID: EMD-7024
タイトル
Cryo-EM structure of the small subunit of Leishmania ribosome bound to paromomycin
マップデータ
primary map
試料
複合体: Leishmania donovani 91S ribosome SSU
タンパク質・ペプチド: x 33種
RNA: x 5種
リガンド: x 3種
機能・相同性
機能・相同性情報
translation regulator activity / ribosome binding / ribosomal small subunit assembly / small ribosomal subunit / cytosolic small ribosomal subunit / rRNA binding / ribosome / structural constituent of ribosome / ribonucleoprotein complex / translation ...translation regulator activity / ribosome binding / ribosomal small subunit assembly / small ribosomal subunit / cytosolic small ribosomal subunit / rRNA binding / ribosome / structural constituent of ribosome / ribonucleoprotein complex / translation / RNA binding / zinc ion binding / metal ion binding 類似検索 - 分子機能
Ribosomal protein S26e / Ribosomal protein S26e superfamily / Ribosomal protein S26e / Ribosomal protein S12e / Ribosomal protein S5, eukaryotic/archaeal / Small (40S) ribosomal subunit Asc1/RACK1 / Ribosomal protein S2, eukaryotic / Ribosomal protein S21e / Ribosomal protein S21e superfamily / Ribosomal protein S21e ...Ribosomal protein S26e / Ribosomal protein S26e superfamily / Ribosomal protein S26e / Ribosomal protein S12e / Ribosomal protein S5, eukaryotic/archaeal / Small (40S) ribosomal subunit Asc1/RACK1 / Ribosomal protein S2, eukaryotic / Ribosomal protein S21e / Ribosomal protein S21e superfamily / Ribosomal protein S21e / 40S Ribosomal protein S10 / S27a-like superfamily / Ribosomal protein S10, eukaryotic/archaeal / Plectin/S10, N-terminal / Plectin/S10 domain / Ribosomal protein S25 / S25 ribosomal protein / Ribosomal protein S2, eukaryotic/archaeal / Ribosomal protein S27a / Ribosomal protein S27a / Ribosomal protein S27a / Ribosomal protein S8e subdomain, eukaryotes / Ribosomal protein S30 / Ribosomal protein S30 / 40S ribosomal protein S29/30S ribosomal protein S14 type Z / Ribosomal protein S3, eukaryotic/archaeal / Ribosomal protein S19e / Ribosomal protein S19e / Ribosomal_S19e / 40S ribosomal protein S4, C-terminal domain / 40S ribosomal protein S4 C-terminus / Ribosomal protein S19A/S15e / Ribosomal protein S8e, conserved site / Ribosomal protein S8e signature. / Ribosomal protein S17e / Ribosomal protein S17e-like superfamily / Ribosomal S17 / Ribosomal protein S6, eukaryotic / 40S ribosomal protein S1/3, eukaryotes / Ribosomal protein S4e, N-terminal / RS4NT (NUC023) domain / Ribosomal S24e conserved site / Ribosomal protein S24e signature. / 40S ribosomal protein S11, N-terminal / Ribosomal_S17 N-terminal / Ribosomal protein S7e / Ribosomal protein S7e / Ribosomal protein S4, KOW domain / Ribosomal protein S4e / Ribosomal protein S4e, central region / Ribosomal protein S4e, central domain superfamily / Ribosomal family S4e / Ribosomal protein S27, zinc-binding domain superfamily / Ribosomal protein S24e / Ribosomal protein S23, eukaryotic/archaeal / Ribosomal protein S24e / Ribosomal protein S6/S6e/A/B/2, conserved site / Ribosomal protein S6e signature. / Ribosomal protein S27 / Ribosomal protein S27 / Ribosomal protein S8e / Ribosomal protein S3Ae / Ribosomal protein S28e conserved site / Ribosomal S3Ae family / Ribosomal protein S28e signature. / Ribosomal S3Ae family / Ribosomal protein S28e / Ribosomal protein S28e / Ribosomal protein S6e / Ribosomal protein S5/S7, eukaryotic/archaeal / Ribosomal protein S6e / Ribosomal protein S6e / Ribosomal protein S13/S15, N-terminal / Ribosomal protein S15P / Ribosomal S13/S15 N-terminal domain / Ribosomal S13/S15 N-terminal domain / Ribosomal protein S4/S9, eukaryotic/archaeal / Ribosomal protein S8e/ribosomal biogenesis NSA2 / Ribosomal protein S8e / Ribosomal protein S14/S29 / Ribosomal protein L7Ae/L30e/S12e/Gadd45 / Ribosomal protein L7Ae/L30e/S12e/Gadd45 family / 50S ribosomal protein L30e-like / Ribosomal protein S2 signature 2. / KH domain / Type-2 KH domain profile. / K Homology domain, type 2 / Ribosomal protein S3, C-terminal / Ribosomal protein S3, C-terminal domain / Ribosomal protein S3, C-terminal domain superfamily / Ribosomal protein S15/S19, conserved site / Ribosomal protein S19 signature. / Ribosomal protein S10 / Ribosomal protein S19/S15 / Ribosomal protein S19/S15, superfamily / Ribosomal protein S19 / Ribosomal protein S2, conserved site / Ribosomal protein S5, N-terminal, conserved site / Ribosomal protein S5 signature. / Ribosomal protein S2 類似検索 - ドメイン・相同性
40S ribosomal protein S5 / 40S ribosomal protein SA / 40S ribosomal protein S7 / 40S ribosomal protein S21, putative / 40S ribosomal protein S15A, putative / 40S ribosomal protein S12 / 40S ribosomal protein S4 / 40S ribosomal protein S23, putative / 40S ribosomal protein S15, putative / 40S ribosomal protein S8 ...40S ribosomal protein S5 / 40S ribosomal protein SA / 40S ribosomal protein S7 / 40S ribosomal protein S21, putative / 40S ribosomal protein S15A, putative / 40S ribosomal protein S12 / 40S ribosomal protein S4 / 40S ribosomal protein S23, putative / 40S ribosomal protein S15, putative / 40S ribosomal protein S8 / 40S ribosomal protein S25 / 40S ribosomal protein S16, putative / 40S ribosomal protein S33, putative / Ribosomal protein S10 / Ribosomal protein S29, putative / 40S ribosomal protein S17, putative / 40S ribosomal protein S26 / 40S ribosomal protein S30 / 40S ribosomal protein S14 / 40S ribosomal protein S2 / 40S ribosomal protein S13, putative / 40S ribosomal protein S3, putative / 40S ribosomal protein S19 protein, putative / 40S ribosomal protein S3a / 60S ribosomal protein L40 / 40S ribosomal protein S18, putative / 40S ribosomal protein S10, putative / 40S ribosomal protein S9, putative / 40S ribosomal protein S24 / 40S ribosomal protein S27-1, putative / 40S ribosomal protein S6 / Guanine nucleotide-binding protein subunit beta-like protein / 40S ribosomal protein S11, putative 類似検索 - 構成要素
ジャーナル: Nat Commun / 年: 2017 タイトル: Atomic resolution snapshot of Leishmania ribosome inhibition by the aminoglycoside paromomycin. 著者: Moran Shalev-Benami / Yan Zhang / Haim Rozenberg / Yuko Nobe / Masato Taoka / Donna Matzov / Ella Zimmerman / Anat Bashan / Toshiaki Isobe / Charles L Jaffe / Ada Yonath / Georgios Skiniotis / 要旨: Leishmania is a single-celled eukaryotic parasite afflicting millions of humans worldwide, with current therapies limited to a poor selection of drugs that mostly target elements in the parasite's ...Leishmania is a single-celled eukaryotic parasite afflicting millions of humans worldwide, with current therapies limited to a poor selection of drugs that mostly target elements in the parasite's cell envelope. Here we determined the atomic resolution electron cryo-microscopy (cryo-EM) structure of the Leishmania ribosome in complex with paromomycin (PAR), a highly potent compound recently approved for treatment of the fatal visceral leishmaniasis (VL). The structure reveals the mechanism by which the drug induces its deleterious effects on the parasite. We further show that PAR interferes with several aspects of cytosolic translation, thus highlighting the cytosolic rather than the mitochondrial ribosome as the primary drug target. The results also highlight unique as well as conserved elements in the PAR-binding pocket that can serve as hotspots for the development of novel therapeutics.