- EMDB-20134: Structure of a drug-like molecule stalled PCSK9 ribosome nascent ... -
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データベース: EMDB / ID: EMD-20134
タイトル
Structure of a drug-like molecule stalled PCSK9 ribosome nascent chain complex (PCSK9-RNC) with AP tRNA and PE tRNA (sample prepared with a short incubation time)
マップデータ
Structure of a drug-like molecule stalled PCSK9 ribosome nascent chain complex (PCSK9-RNC) with AP tRNA and PE tRNA (sample prepared with a short incubation time)
試料
複合体: Structure of a drug-like molecule stalled PCSK9 ribosome nascent chain complex (PCSK9-RNC) with AP tRNA and PE tRNA (sample prepared with a short incubation time)
National Institutes of Health/National Human Genome Research Institute
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.
ダウンロード / ファイル: emd_20134.map.gz / 形式: CCP4 / 大きさ: 421.9 MB / タイプ: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
注釈
Structure of a drug-like molecule stalled PCSK9 ribosome nascent chain complex (PCSK9-RNC) with AP tRNA and PE tRNA (sample prepared with a short incubation time)
ボクセルのサイズ
X=Y=Z: 1.22 Å
密度
表面レベル
By EMDB: 0.3 / ムービー #1: 0.3
最小 - 最大
-0.38621876 - 1.2164409
平均 (標準偏差)
0.0076140556 (±0.072721496)
対称性
空間群: 1
詳細
EMDB XML:
マップ形状
Axis order
X
Y
Z
Origin
0
0
0
サイズ
480
480
480
Spacing
480
480
480
セル
A=B=C: 585.60004 Å α=β=γ: 90.0 °
CCP4マップ ヘッダ情報:
mode
Image stored as Reals
Å/pix. X/Y/Z
1.22
1.22
1.22
M x/y/z
480
480
480
origin x/y/z
0.000
0.000
0.000
length x/y/z
585.600
585.600
585.600
α/β/γ
90.000
90.000
90.000
MAP C/R/S
1
2
3
start NC/NR/NS
0
0
0
NC/NR/NS
480
480
480
D min/max/mean
-0.386
1.216
0.008
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添付データ
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試料の構成要素
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全体 : Structure of a drug-like molecule stalled PCSK9 ribosome nascent ...
全体
名称: Structure of a drug-like molecule stalled PCSK9 ribosome nascent chain complex (PCSK9-RNC) with AP tRNA and PE tRNA (sample prepared with a short incubation time)
要素
複合体: Structure of a drug-like molecule stalled PCSK9 ribosome nascent chain complex (PCSK9-RNC) with AP tRNA and PE tRNA (sample prepared with a short incubation time)
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超分子 #1: Structure of a drug-like molecule stalled PCSK9 ribosome nascent ...
超分子
名称: Structure of a drug-like molecule stalled PCSK9 ribosome nascent chain complex (PCSK9-RNC) with AP tRNA and PE tRNA (sample prepared with a short incubation time) タイプ: complex / ID: 1 / 親要素: 0 / 含まれる分子: #1