3D Computational Modeling of Human P-gp NBD2 with Papyriferic Acid Derivatives

다국어 초록 (Multilingual Abstract)

Human P-gp is one of the protein responsible for the multidrug resistance (MDR) develpment. MDR is a major cause of the cancer chemotherapy. In this paper, we performed homology modeling, docking study of papayriferic acid into the P-gp nucleotide binding domain (NBD2). For human P-gp, X-ray crystal structure is not known yet. We developed homology model for human NBD2 using HlyB ABC transporter structure (PDB code: 1XEF, resolution 2.5 ${\AA}$). Docking study was performed using Autodock. Docking result was analyzed, which shows that ligand docks into steroid binding site and interacts through hydrophobic and hydrophilic interactions.

참고문헌 (Reference)

1 N. Eswar, "Tools for comparative protein structure modeling and analysis.”" 31 : 3375-3380, 2003

2 H. Glavinas, "The role of ABC transporters in drug resistance, metabolism and toxicity" 1 : 27-42, 2004

3 K. Ueda, "The human multidrug resistance (Mdr1) gene - cDNA cloning and transcription initiation" 262 : 505-508, 1987

4 S. F. Zhou, "Structure, function and regulation of Pglycoprotein and its clinical relevance in drug disposition" 38 : 802-832, 2008

5 "S. H. R. SYBYL8.1; Tripos Inc., St. Louis, MO 63144, USA"

6 J. Xiong, "Papyriferic acid derivatives as reversal agents of multidrug resistance in cancer cells" 18 : 2964-2975, 2010

7 S. Mares-Sámano, "Identification of putative steroid-binding sites in human ABCB1 and ABCG2" 44 : 3601-3611, 2009

8 F. Thiebaut, "Cellularlocalization of the multidrug-resistance gene-product p-glycoprotein in normal human-tissues" 84 : 7735-7738, 1987

9 G. M. Morris, "Automated docking using a Lamarckian genetic algorithm and an empirical binding free energy function" 19 : 1639-1662, 1998

10 F. J. Sharom, "ABC multidrug transporters: structure, function and role in chemoresistance" 9 : 105-127, 2008