Cyclin-Dependent Kinase 12 (CDK12), Human Kinase Domain; A Target Enabling Package

A description of the materials and methods is included within the TEP datasheet. Cyclin-dependent kinase 12 (CDK12) phosphorylates RNA Pol II C-terminal domain (CTD) to promote transcriptional elongation of large DNA damage response genes. CDK12 is frequently mutated or amplified in cancer and its l...

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Rannpháirtithe: Bullock, A
Formáid: Dataset
Foilsithe / Cruthaithe: University of Oxford 2018
Ábhair:
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author2 Bullock, A
author_facet Bullock, A
collection OXFORD
description A description of the materials and methods is included within the TEP datasheet. Cyclin-dependent kinase 12 (CDK12) phosphorylates RNA Pol II C-terminal domain (CTD) to promote transcriptional elongation of large DNA damage response genes. CDK12 is frequently mutated or amplified in cancer and its loss sensitises cells to DNA damage. Here we present 3 crystal structures of the human CDK12/CycK complex including apo, AMP-PNP and covalent inhibitor complexes. Kinase assays compare domain truncations and report the Km values for substrate. THZ531 is presented as a potent and selective inhibitor of CDK12 with nanomolar activity in leukemic cell lines.
first_indexed 2024-03-07T03:56:54Z
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spelling oxford-uuid:c32f1fc0-241b-4af7-813f-f5fb26c7d23c2022-03-27T06:14:34ZCyclin-Dependent Kinase 12 (CDK12), Human Kinase Domain; A Target Enabling PackageDatasethttp://purl.org/coar/resource_type/c_ddb1uuid:c32f1fc0-241b-4af7-813f-f5fb26c7d23cChemical BiologyStructural GenomicsDrug DiscoveryORA DepositUniversity of Oxford2018Bullock, ADixon-Clarke, SElkins, JHannett, NManz, THao, MBartkowiak, BGreenleaf, AMarto, JGeyer, MYoung, RGray, NMorin, GCheng, SZhang, TKwiatkowski, NOlson, CAbraham, BGreifenberg, AFicarro, SLiang, YA description of the materials and methods is included within the TEP datasheet. Cyclin-dependent kinase 12 (CDK12) phosphorylates RNA Pol II C-terminal domain (CTD) to promote transcriptional elongation of large DNA damage response genes. CDK12 is frequently mutated or amplified in cancer and its loss sensitises cells to DNA damage. Here we present 3 crystal structures of the human CDK12/CycK complex including apo, AMP-PNP and covalent inhibitor complexes. Kinase assays compare domain truncations and report the Km values for substrate. THZ531 is presented as a potent and selective inhibitor of CDK12 with nanomolar activity in leukemic cell lines.
spellingShingle Chemical Biology
Structural Genomics
Drug Discovery
Cyclin-Dependent Kinase 12 (CDK12), Human Kinase Domain; A Target Enabling Package
title Cyclin-Dependent Kinase 12 (CDK12), Human Kinase Domain; A Target Enabling Package
title_full Cyclin-Dependent Kinase 12 (CDK12), Human Kinase Domain; A Target Enabling Package
title_fullStr Cyclin-Dependent Kinase 12 (CDK12), Human Kinase Domain; A Target Enabling Package
title_full_unstemmed Cyclin-Dependent Kinase 12 (CDK12), Human Kinase Domain; A Target Enabling Package
title_short Cyclin-Dependent Kinase 12 (CDK12), Human Kinase Domain; A Target Enabling Package
title_sort cyclin dependent kinase 12 cdk12 human kinase domain a target enabling package
topic Chemical Biology
Structural Genomics
Drug Discovery