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The Key Residues of Active Sites on the Catalytic Fragment for Paclitaxel Interacting with Poly (ADP-Ribose) Polymerase
Wang, Yue1; Bian, Fuyong1; Deng, Shengrong; Shi, Qiang2; Ge, Maofa2; Wang, Shu2; Zhang, Xingkang2; Xu, Sichuan1,2
2011-06-01
Source PublicationJOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
ISSN0739-1102
Volume28Issue:6Pages:881-893
AbstractPoly(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.
KeywordBinding Pocket Active Site Paclitaxel Poly(Adp-ribose) Polymerase Md Simulation Dft
Indexed BySCI
Language英语
WOS IDWOS:000290010900004
PublisherADENINE PRESS
Citation statistics
Cited Times:14[WOS]   [WOS Record]     [Related Records in WOS]
Document Type期刊论文
Identifierhttp://ir.iccas.ac.cn/handle/121111/72580
Collection中国科学院化学研究所
Corresponding AuthorXu, Sichuan
Affiliation1.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
Recommended Citation
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.
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