中国科学院机构知识库网格
Chinese Academy of Sciences Institutional Repositories Grid
The Key Residues of Active Sites on the Catalytic Fragment for Paclitaxel Interacting with Poly (ADP-Ribose) Polymerase

文献类型:期刊论文

作者Wang, Yue1; Bian, Fuyong1; Deng, Shengrong; Shi, Qiang2; Ge, Maofa2; Wang, Shu2; Zhang, Xingkang2; Xu, Sichuan1,2
刊名JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
出版日期2011-06-01
卷号28期号:6页码:881-893
关键词Binding Pocket Active Site Paclitaxel Poly(Adp-ribose) Polymerase Md Simulation Dft
ISSN号0739-1102
英文摘要Poly(ADP-ribose) polymerase (PARP) is regarded as a target protein for paclitaxel (PTX) to bind. An important issue is to identify the key residues as active sites for PTX interacting with PARP, which will help to understand the potential drug activity of PTX against cancer cells. Using docking method and MD simulation, we have constructed a refined structure of PTX docked on the catalytic function domain of PARP (PDB code: 1A26). The residues Glu327(988), Tyr246(907), Lys242(903), His165(826), Asp105(766), Gln102(763) and Gln98(759) in PARP are identified as potential sites involved in interaction with PTX according to binding energy (E-b) between PTX and single residue calculated with B3LYP/6-31G(d,p). These residues form an active binding pocket located on the surface of the catalytic fragment, possibly interacting with the required groups of PTX leading to its activity against cancer cells. It is noted that most of the active sites make conatct with the "southern hemisphere" of PTX except for one residue, Tyr246(907), which interacts with the "nourthern hemisphere" of PTX. The conformation of PTX in complex with the catalytic fragment is observed as being T-shaped, similar to that complexed with beta-tubulin. The total E-b of -269.9 kJ/mol represents the potent interaction between PTX and the catalytic fragment, implying that PTX can readily bind to the active pocket. The tight association of PTX with the catalytic fragment would inhibit PARP activation, suggesting a potential application of PTX as an effective anti neoplastic agent.
语种英语
WOS记录号WOS:000290010900004
出版者ADENINE PRESS
源URL[http://ir.iccas.ac.cn/handle/121111/72579]  
专题中国科学院化学研究所
通讯作者Xu, Sichuan
作者单位1.Yunnan Univ, Key Lab Educ, Minist Med Chem Nat Resource, Coll Chem Sci & Technol, Kunming 650091, Peoples R China
2.Chinese Acad Sci, State Key Lab Struct Chem Unstable & Stable Speci, Beijing Natl Lab Mol Sci, Inst Chem, Beijing 100190, Peoples R China
推荐引用方式
GB/T 7714
Wang, Yue,Bian, Fuyong,Deng, Shengrong,et al. The Key Residues of Active Sites on the Catalytic Fragment for Paclitaxel Interacting with Poly (ADP-Ribose) Polymerase[J]. JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS,2011,28(6):881-893.
APA Wang, Yue.,Bian, Fuyong.,Deng, Shengrong.,Shi, Qiang.,Ge, Maofa.,...&Xu, Sichuan.(2011).The Key Residues of Active Sites on the Catalytic Fragment for Paclitaxel Interacting with Poly (ADP-Ribose) Polymerase.JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS,28(6),881-893.
MLA Wang, Yue,et al."The Key Residues of Active Sites on the Catalytic Fragment for Paclitaxel Interacting with Poly (ADP-Ribose) Polymerase".JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS 28.6(2011):881-893.

入库方式: OAI收割

来源:化学研究所

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