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PDBsum entry 7b5o
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Transcription
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PDB id
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7b5o
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Contents |
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65 a.a.
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281 a.a.
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297 a.a.
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References listed in PDB file
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Key reference
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Title
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2.5 å-Resolution structure of human cdk-Activating kinase bound to the clinical inhibitor icec0942.
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Authors
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B.J.Greber,
J.Remis,
S.Ali,
E.Nogales.
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Ref.
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Biophys J, 2021,
120,
677-686.
[DOI no: ]
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PubMed id
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Abstract
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The human CDK-activating kinase (CAK), composed of CDK7, cyclin H, and MAT1, is
involved in the control of transcription initiation and the cell cycle. Because
of these activities, it has been identified as a promising target for cancer
chemotherapy. A number of CDK7 inhibitors have entered clinical trials, among
them ICEC0942 (also known as CT7001). Structural information can aid in
improving the affinity and specificity of such drugs or drug candidates,
reducing side effects in patients. Here, we have determined the structure of the
human CAK in complex with ICEC0942 at 2.5 Å-resolution using cryogenic
electron microscopy. Our structure reveals conformational differences of
ICEC0942 compared with previous X-ray crystal structures of the CDK2-bound
complex, and highlights the critical ability of cryogenic electron microscopy to
resolve structures of drug-bound protein complexes without the need to
crystalize the protein target.
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