Crystal structure of pyridoxal kinase in complex with roscovitine and derivatives
文献类型：期刊论文
| 作者 | Tang, L; Li, MH; Cao, P; Wang, F; Chang, WR; Bach, S; Reinhardt, J; Ferandin, Y; Galons, H; Wan, YQ |
| 刊名 | Journal of biological chemistry
 |
| 出版日期 | 2005-09-02 |
| 卷号 | 280期号:35页码:31220-31229 |
| ISSN号 | 0021-9258 |
| DOI | 10.1074/jbc.m500805200 |
| 通讯作者 | Jiang, t() |
| 英文摘要 | 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 b-6, 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, n-6-methyl-(r)- roscovitine, and o-6-(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. |
| WOS关键词 | CYCLIN-DEPENDENT KINASES ; CDK INHIBITORS ; R-ROSCOVITINE ; PROTEIN ; CANCER ; PROGRAM ; BRAIN ; IDENTIFICATION ; DEREGULATION ; DISEASE |
| WOS研究方向 | Biochemistry & Molecular Biology |
| WOS类目 | Biochemistry & Molecular Biology |
| 语种 | 英语 |
| WOS记录号 | WOS:000231487800069 |
| 出版者 | AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC |
| URI标识 | http://www.irgrid.ac.cn/handle/1471x/2377361 |
| 专题 | 中国科学院大学 |
| 通讯作者 | Jiang, T |
| 作者单位 | 1.Chinese Acad Sci, Natl Lab Biomacromol, Inst Biophys, Beijing 100101, Peoples R China 2.CNRS, Cell Cycle Grp, UPS 2682, F-29682 Roscoff, Bretagne, France 3.UMR Mer & Sante 7150, Biol Stn, F-29682 Roscoff, Bretagne, France 4.Univ Paris 05, Lab Chim Organ 2, F-75270 Paris, France 5.Novartis Res Fdn, Genomics Inst, Dept Chem, San Diego, CA 92121 USA 6.Chinese Acad Sci, Grad Sch, Beijing 100039, Peoples R China |
| 推荐引用方式 GB/T 7714 | Tang, L,Li, MH,Cao, P,et al. Crystal structure of pyridoxal kinase in complex with roscovitine and derivatives[J]. Journal of biological chemistry,2005,280(35):31220-31229. |
| APA | Tang, L.,Li, MH.,Cao, P.,Wang, F.,Chang, WR.,...&Liang, DC.(2005).Crystal structure of pyridoxal kinase in complex with roscovitine and derivatives.Journal of biological chemistry,280(35),31220-31229. |
| MLA | Tang, L,et al."Crystal structure of pyridoxal kinase in complex with roscovitine and derivatives".Journal of biological chemistry 280.35(2005):31220-31229. |
入库方式： iSwitch采集
来源：中国科学院大学
浏览0
下载0
收藏0
其他版本
除非特别说明，本系统中所有内容都受版权保护，并保留所有权利。