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Structures of human telomerase with BIBR1532 reveal novel mechanism of inhibition.
Nature Chemical Biology · · Journal Article · Open access
Wang, Liu + more
Abstract ↗AI summary
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Nine cryo-EM structures of human telomerase with BIBR1532 show the inhibitor binds a previously unknown pocket between TERT finger and palm, blocking repeat addition.
- Why it matters: Telomerase is aberrantly upregulated in most tumor cells, but lack of inhibitor-bound human structures has limited structure-based drug design and optimization.
- What they did: The team determined nine cryo-electron microscopy structures of human telomerase with and without BIBR1532, a highly selective small-molecule inhibitor.
- The result: BIBR1532 inhibits each step of telomere repeat nucleotide addition, disproportionately affecting the rate-limiting first step, and the structures suggest a rational design path for improved inhibitors.
The findingWhy it mattersWhat they didThe result
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