EMDB/PDB/SASBDBから引用されている文献のデータベース

キーワード
構造解析手法	All X線回折 NMR 電子顕微鏡小角散乱中性子線回折線維回折粉末回折赤外分光 EPR FRET 理論モデルハイブリッド
著者・登録者
ジャーナル
IF	>30 >20 >10 >5 all

タイトル	Structures of human telomerase with BIBR1532 reveal novel mechanism of inhibition.
ジャーナル・号・ページ	Nat Chem Biol, Year 2026
掲載日	2026年6月2日
著者	Yuqing Wang / Baocheng Liu / Yao He / Juli Feigon /
PubMed 要旨	Human telomerase processively adds telomeric repeats (dGGTTAG) to chromosome 3'-ends to maintain telomere length. While mostly absent in somatic cells, telomerase is aberrantly upregulated in most ...Human telomerase processively adds telomeric repeats (dGGTTAG) to chromosome 3'-ends to maintain telomere length. While mostly absent in somatic cells, telomerase is aberrantly upregulated in most tumor cells to sustain cellular immortality, making it a promising oncology target. However, to date there are no reported structures of human telomerase with inhibitor, impeding structure-based drug design and optimization. We report nine cryo-electron microscopy structures of human telomerase with and without BIBR1532, a highly selective small-molecule telomerase inhibitor. Unexpectedly, BIBR1532 binds a previously unknown pocket between TERT finger and palm. BIBR1532 inhibits each step but disproportionately affects the rate-limiting first step of telomere repeat nucleotide addition. The structures reveal a rigid finger that explains telomerase's slow rate and low fidelity. Our study provides insights into telomerase catalytic mechanism and its inhibition by BIBR1532, explains why prior BIBR derivatives did not improve potency and suggests a rational approach for design of small-molecule telomerase inhibitors.
リンク	Nat Chem Biol / PubMed:42230822
手法	EM (単粒子)
解像度	2.7 - 3.4 Å
構造データ	72111 9q0z EMDB-72111, PDB-9q0z: Human telomerase catalytic core with shelterin protein TPP1, BIBR1532 and DNA primer ending in AGGG 手法: EM (単粒子) / 解像度: 3.1 Å 72112 9q10 EMDB-72112, PDB-9q10: Human telomerase catalytic core with shelterin protein TPP1, dTpNHpp and DNA primer ending in AGGG 手法: EM (単粒子) / 解像度: 2.9 Å 72113 9q11 EMDB-72113, PDB-9q11: Human telomerase catalytic core with shelterin protein TPP1, BIBR1532, dTpNHpp and DNA primer ending in AGGG 手法: EM (単粒子) / 解像度: 2.9 Å 72114 9q12 EMDB-72114, PDB-9q12: Human telomerase catalytic core with shelterin protein TPP1 and DNA primer ending in TTAG 手法: EM (単粒子) / 解像度: 2.8 Å 72115 9q14 EMDB-72115, PDB-9q14: Human telomerase catalytic core with shelterin protein TPP1, BIBR1532 and DNA primer ending in TTAG 手法: EM (単粒子) / 解像度: 3.0 Å 72117 9q16 EMDB-72117, PDB-9q16: Human telomerase catalytic core with shelterin protein TPP1, dGpNHpp and DNA primer ending in TTAG 手法: EM (単粒子) / 解像度: 2.7 Å 72118 9q17 EMDB-72118, PDB-9q17: Class I (T1D0+) of Human telomerase catalytic core with shelterin protein TPP1, BIBR1532, dGpNHpp and DNA primer ending in TTAG 手法: EM (単粒子) / 解像度: 3.3 Å 72119 9q18 EMDB-72119, PDB-9q18: Class II ("T0D0") of Human telomerase catalytic core with shelterin protein TPP1, BIBR1532, dGpNHpp and DNA primer ending in TTAG 手法: EM (単粒子) / 解像度: 3.3 Å 72120 9q19 EMDB-72120, PDB-9q19: Class III (T1D0) of Human telomerase catalytic core with shelterin protein TPP1, BIBR1532, dGpNHpp and DNA primer ending in TTAG 手法: EM (単粒子) / 解像度: 3.4 Å
化合物	ChemComp-55C: 2-{[(2E)-3-(naphthalen-2-yl)but-2-enoyl]amino}benzoic acid ChemComp-1FZ: 5'-O-[(R)-hydroxy{[(R)-hydroxy(phosphonooxy)phosphoryl]amino}phosphoryl]thymidine ChemComp-XG4: 2'-deoxy-5'-O-[(R)-hydroxy{[(R)-hydroxy(phosphonooxy)phosphoryl]amino}phosphoryl]guanosine
由来	homo sapiens (ヒト)
キーワード	RNA BINDING PROTEIN/RNA/DNA / DNA polymerase / Reverse Transcriptase / Ribonucleoprotein / RNA BINDING PROTEIN / RNA BINDING PROTEIN-RNA-DNA complex