Structural insights for producing CK2α1-specific inhibitors
| Autor: | Takayoshi Kinoshita, Masato Tsuyuguchi, Tetsuko Nakaniwa, Isao Nakanishi, Akira Hirasawa |
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| Rok vydání: | 2019 |
| Předmět: |
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Molecular Conformational change Protein subunit Clinical Biochemistry Pharmaceutical Science Crystal structure 01 natural sciences Biochemistry Catalysis chemistry.chemical_compound Drug Discovery Humans Amino Acid Sequence Hematein Casein Kinase II Molecular Biology 010405 organic chemistry Drug discovery Organic Chemistry 0104 chemical sciences 010404 medicinal & biomolecular chemistry chemistry Molecular Medicine Casein kinase 2 Selectivity |
| Zdroj: | Bioorganicmedicinal chemistry letters. 30(2) |
| ISSN: | 1464-3405 |
| Popis: | Casein kinase 2 catalytic subunit (CK2α) is classified into two subtypes CK2α1 and CK2α2. CK2α1 is a drug discovery target, whereas CK2α2 is an off-target of CK2α1 inhibitors. High amino acid sequence homology between these subtypes hampers efforts to produce ATP competitive inhibitors that are highly selective to CK2α1. Hematein was identified previously as a non-ATP-competitive inhibitor for CK2α1, whereas this compound acts as an ATP competitive CK2α2 inhibitor. Crystal structures of CK2α1 and CK2α2 in complex with hematein revealed distinct binding features that provide structural insights for producing CK2α1-selective inhibitors. |
| Databáze: | OpenAIRE |
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