Database of articles cited by EMDB/PDB/SASBDB data

Keywords
Structure methods	All X-ray diffraction NMR electron microscopy small angle scattering neutron diffraction fiber diffraction powder diffraction infrared spectroscopy EPR fluorescence transfer theoretical model Hybrid
Author
Journal
IF	>30 >20 >10 >5 all

Title	Structures of human telomerase with BIBR1532 reveal novel mechanism of inhibition.
Journal, issue, pages	Nat Chem Biol, Year 2026
Publish date	Jun 2, 2026
Authors	Yuqing Wang / Baocheng Liu / Yao He / Juli Feigon /
PubMed Abstract	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.
External links	Nat Chem Biol / PubMed:42230822
Methods	EM (single particle)
Resolution	2.7 - 3.4 Å
Structure data	72111 9q0z EMDB-72111, PDB-9q0z: Human telomerase catalytic core with shelterin protein TPP1, BIBR1532 and DNA primer ending in AGGG Method: EM (single particle) / Resolution: 3.1 Å 72112 9q10 EMDB-72112, PDB-9q10: Human telomerase catalytic core with shelterin protein TPP1, dTpNHpp and DNA primer ending in AGGG Method: EM (single particle) / Resolution: 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 Method: EM (single particle) / Resolution: 2.9 Å 72114 9q12 EMDB-72114, PDB-9q12: Human telomerase catalytic core with shelterin protein TPP1 and DNA primer ending in TTAG Method: EM (single particle) / Resolution: 2.8 Å 72115 9q14 EMDB-72115, PDB-9q14: Human telomerase catalytic core with shelterin protein TPP1, BIBR1532 and DNA primer ending in TTAG Method: EM (single particle) / Resolution: 3.0 Å 72117 9q16 EMDB-72117, PDB-9q16: Human telomerase catalytic core with shelterin protein TPP1, dGpNHpp and DNA primer ending in TTAG Method: EM (single particle) / Resolution: 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 Method: EM (single particle) / Resolution: 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 Method: EM (single particle) / Resolution: 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 Method: EM (single particle) / Resolution: 3.4 Å
Chemicals	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
Source	homo sapiens (human)
Keywords	RNA BINDING PROTEIN/RNA/DNA / DNA polymerase / Reverse Transcriptase / Ribonucleoprotein / RNA BINDING PROTEIN / RNA BINDING PROTEIN-RNA-DNA complex