| Crystal structure of pyridoxal kinase in complex with roscovitine and derivatives. | |
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MedLine Citation:
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PMID: 15985434 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Pyridoxal kinase (PDXK) catalyzes the phosphorylation of pyridoxal, pyridoxamine, and pyridoxine in the presence of ATP and Zn2+. This constitutes an essential step in the synthesis of pyridoxal 5'-phosphate (PLP), the active form of vitamin B6, a cofactor for over 140 enzymes. (R)-Roscovitine (CYC202, Seliciclib) is a relatively selective inhibitor of cyclin-dependent kinases (CDKs), currently evaluated for the treatment of cancers, neurodegenerative disorders, renal diseases, and several viral infections. Affinity chromatography investigations have shown that (R)-roscovitine also interacts with PDXK. To understand this interaction, we determined the crystal structure of PDXK in complex with (R)-roscovitine, N6-methyl-(R)-roscovitine, and O6-(R)-roscovitine, the two latter derivatives being designed to bind to PDXK but not to CDKs. Structural analysis revealed that these three roscovitines bind similarly in the pyridoxal-binding site of PDXK rather than in the anticipated ATP-binding site. The pyridoxal pocket has thus an unexpected ability to accommodate molecules different from and larger than pyridoxal. This work provides detailed structural information on the interactions between PDXK and roscovitine and analogs. It could also aid in the design of roscovitine derivatives displaying strict selectivity for either PDXK or CDKs. |
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Authors:
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Lin Tang; Ming-Hui Li; Peng Cao; Feng Wang; Wen-Rui Chang; Stéphane Bach; Jens Reinhardt; Yoan Ferandin; Hervé Galons; Yongqin Wan; Nathanael Gray; Laurent Meijer; Tao Jiang; Dong-Cai Liang |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2005-06-28 |
Journal Detail:
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Title: The Journal of biological chemistry Volume: 280 ISSN: 0021-9258 ISO Abbreviation: J. Biol. Chem. Publication Date: 2005 Sep |
Date Detail:
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Created Date: 2005-08-29 Completed Date: 2005-10-25 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 2985121R Medline TA: J Biol Chem Country: United States |
Other Details:
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Languages: eng Pagination: 31220-9 Citation Subset: IM |
Affiliation:
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National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, 15 Datun Road, Chaoyang District, Beijing 100101, China. |
| Data Bank Information | |
Bank Name/Acc. No.:
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PDB/1YGJ; 1YGK; 1YHJ |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Binding Sites Crystallography, X-Ray Ligands Macromolecular Substances Models, Molecular Molecular Structure Nuclear Magnetic Resonance, Biomolecular Protein Kinase Inhibitors / chemistry*, metabolism Protein Structure, Tertiary* Purines / chemistry*, metabolism Pyridoxal Kinase / chemistry*, metabolism Swine |
| Chemical | |
Reg. No./Substance:
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0/Ligands; 0/Macromolecular Substances; 0/Protein Kinase Inhibitors; 0/Purines; 0/roscovitine; EC 2.7.1.35/Pyridoxal Kinase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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