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| {{STRUCTURE_2rku| PDB=2rku | SCENE= }} | | {{STRUCTURE_2rku| PDB=2rku | SCENE= }} |
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| '''Structure of PLK1 in complex with BI2536'''
| | ===Structure of PLK1 in complex with BI2536=== |
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| ==Overview==
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| Polo-like kinase 1 is an important regulator of cell cycle progression whose over-expression is often associated with oncogenesis. Polo-like kinase 1 hence represents an attractive target for cancer intervention. BI 2536 (Boehringer Ingelheim, Ingelheim, Germany), a Polo-like kinase 1 inhibitor currently in clinical trials, exhibits nanomolar potency against Polo-like kinase isoforms and high selectivity against other kinases. We have previously published the crystal structures of the Polo-like kinase 1 domain in complex with AMPPNP and an Aurora A inhibitor. In this work, we present the co-crystal structure of Polo-like kinase 1 with BI 2536. The structure, in combination with selectivity data for BI 2536 and related compounds, illustrates important features for potency and selectivity. In particular, we show that the methoxy group of BI 2536 is an important specificity determinant against non-Polo-like kinases by taking advantage of a small pocket generated by Leu 132 in the hinge region of Polo-like kinase 1. The work presented here provides a framework for structure-based drug design of Polo-like kinase 1-specific inhibitors.
| | The line below this paragraph, {{ABSTRACT_PUBMED_18005335}}, adds the Publication Abstract to the page |
| | (as it appears on PubMed at http://www.pubmed.gov), where 18005335 is the PubMed ID number. |
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| | {{ABSTRACT_PUBMED_18005335}} |
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| ==About this Structure== | | ==About this Structure== |
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| [[Category: Structure of plk1]] | | [[Category: Structure of plk1]] |
| [[Category: Transferase]] | | [[Category: Transferase]] |
| ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 17:06:26 2008'' | | |
| | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Jul 27 21:20:51 2008'' |
