Abstract：[Abstract] Objective To investigate the binding modes between actinonin and peptide deformylases and to characterize the informations about how to design the specific HsPDF inhibitor. Methods The combination of molecular dynamics simulation and MM/GBSA free energy calculation was employed to study the interactions between several PDF enzymes and actinonin. The detailed interactions of each residues of protein and actinonin were calculated by MM/GBSA free energy decomposition. Results Three important differences in actinonin binding to PDFs were obtained as followed: actinonin had stronger binding interaction with the motif 1 of HsPDF than the motif 2, while actinonin had lower binding interaction with the motif 1 than the motif 2 for PDF1A and PDF2. Moreover, actinonin had stronger binding affinities with Leu131 and Met145 of HsPDF, but had no interaction with the corresponding ones of PDF1A and PDF2. In addition, actinonin interacted strongly with Trp207 of HsPDF but weakly with the corresponding residue of PDF1A and PDF2. Conclusion By using the method of molecular dynamics simulation, the interaction of actinonin and PDF model are studied, differences of HsPDF and PDF in the active site with other types are expounded, based on the design thinking of specific HsPDF inhibitors of actinonin is proposed.
高 剑 王 涛 孙 杰 牟 杰. Actinonin与肽脱甲酰基酶作用模式的分子动力学模拟研究[J]. 中国医药导报, 2016, 13(3): 21-26.
GAO Jian WANG Tao SUN Jie MOU Jie. Molecular dynamics simulation on the molecular interactions of peptide deformylase and actinonin. 中国医药导报, 2016, 13(3): 21-26.
[参考文献]
[1] Leeds JA，Dean CR. Peptide deformylase as an antibacterial target：a critical assessment [J]. Current Opinion in Pharmacology，2006，6（5）：445-452.
[2] Rajagopalan PTR，Yu XC，Pei D. Peptide deformylase：a new type of mononuclear iron protein [J]. Journal of the American Chemical Society，1997，119（50）：12418-12419.
[3] Guilloteau JP，Mathieu M，Giglione C，et al. The crystal structures of four peptide deformylases bound to the antibiotic actinonin reveal two distinct types：a platform for the structure-based design of antibacterial agents [J]. J Mol Biol，2002，320（5）：951-962.
[4] Giglione C，Pierre M，Meinnel T. Peptide deformylase as a target for new generation，broad spectrum antimicrobial agents [J]. Mol Microbiol，2000，36（6）：1197-1205.
[5] Giglione C，Meinnel T. Peptide deformylase as an emerging target for antiparasitic agents [J]. Expert Opin Ther Targets，2001，5（1）：41-57.
[6] Meinnel T，Patiny L，Ragusa S，et al. Design and synthesis of substrate analogue inhibitors of peptide deformylase [J]. Biochemistry，1999，38（14）：4287-4295.
[7] Chen DZ，Patel DV，Hackbarth CJ，et al. Actinonin，a naturally occurring antibacterial agent，is a potent deformylase inhibitor [J]. Biochemistry，2000，39（6）：1256-1262.
[8] Hu X，Nguyen KT，Verlinde CL，et al. Structure-based design of a macrocyclic inhibitor for peptide deformylase [J]. Journal of Medicinal Chemistry，2003，46（18）：3771-3774.
[9] Lofland D，Difuntorum S，Waller A，et al. In vitro antibacterial activity of the peptide deformylase inhibitor BB-83698 [J]. Journal of Antimicrobial Chemotherapy，2004，53（4）：664-668.
[10] O'Dwyer K，Hackel M，Hightower S，et al. Comparative analysis of the antibacterial activity of a novel peptide deformylase inhibitor，GSK1322322 [J]. Antimicrob Agents Che-mother，2013，57（5）：2333-2342.
[11] Giglione C，Serero A，Pierre M，et al. Identification of eukaryotic peptide deformylases reveals universality of N-terminal protein processing mechanisms [J]. EMBO J，2000，19（21）：5916-5929.
[12] Meinnel T. Peptide deformylase of eukaryotic protists：a target for new antiparasitic agents? [J]. Parasitology Today，2000，16（4）：165-168.
[13] Spencer AC，Spremulli LL. Interaction of mitochondrialinitiation factor 2 with mitochondrial fMet-tRNA [J]. Nucleic Acids Research，2004，32（18）：5464-5470.
[14] Liao HX，Spremulli LL. Identification and initial characterization of translational initiation factor 2 from bovine mitochondria [J]. Journal of Biological Chemistry，1990，265（23）：13618-13622.
[15] Pereira-Castro I，Costa LTd，Amorim A，et al. Transcriptional regulation of the human mitochondrial peptide deformylase （PDF） [J]. Biochemical and Biophysical Research Communications，2012，421（4）：825-831.
[16] Liu CC，Liu BG，Yang ZW，et al. Genome-wide identification and in silico analysis of poplar peptide deformylases [J]. International Journal of Molecular Sciences，2012，13（4）：5112-5124.
[17] Escobar-Alvarez S，Gardner J，Sheth A，et al. Inhibition of human peptide deformylase disrupts mitochondrial function [J]. Mol Cell Biol，2010，30（21）：5099-5109.
[18] Randhawa H，Chikara S，Gehring D，et al. Overexpression of peptide deformylase in breast，colon，and lung cancers [J]. BMC Cancer，2013，13（1）：1-7.
[19] 林超，罗学刚，邢莹莹，等.人肽脱甲酰基酶基因pdf与肿瘤细胞生长的相关性[J].中国药科大学学报，2006， 37（5）：474-478.
[20] Lee MD，Antczak C，Li Y，et al. A new human peptide deformylase inhibitable by actinonin [J]. Biochemical and Biophysical Research Communications，2003，312（2）：309-315.
[21] Han JH，Choi YS，Kim WJ，et al. Codon optimization enhances protein expression of human peptide deformylase in E.coli [J]. Protein Expression and Purification，2010，70（2）：224-230.
[22] Escobar-Alvarez S，Goldgur Y，Yang G，et al. Structure and activity of human mitochondrial peptide deformylase，a novel cancer target [J]. J Mol Biol，2009，387（5）：1211-1228.
[23] Gao J，Wang L，Kang SG，et al. Size-dependent impact of CNTs on dynamic properties of calmodulin [J]. Nanoscale，2014，6（21）：12828-12837.
[24] Hou T，Zhang W，Case DA，et al. Characterization of domain-peptide interaction interface：a case study on the Amphiphysin-1 SH3 domain [J]. Journal of Molecular Biology，2008，376（4）：1201-1214.
[25] Hou T，McLaughlin W，Lu B，et al. Prediction of binding affinities between the human Amphiphysin-1 SH3 domain and its peptide ligands using homology modeling，molecular dynamics and molecular field analysis [J]. Journal of Proteome Research，2005，5（1）：32-43.
[26] Hou T，Wang J，Li Y，et al. assessing the performance of the MM/PBSA and MM/GBSA methods. 1. The accuracy of binding free energy calculations based on molecular dynamics simulations [J]. Journal of Chemical Information and Modeling，2010，51（1）：69-82.
[27] 崔巍，张怀，计明娟.新型二氟甲基磷酸类酪氨酸蛋白磷酸酯酶1B抑制剂的分子动力学模拟和结合自由能计算[J].物理化学学报，2009，25（4）：668-676.
[28] 侯廷军，徐筱杰.基于分子动力学模拟和连续介质模型的自由能计算方法[J].化学进展，2004，16（2）：153-158.
[29] 罗芳，高剑，成元华，等.葡萄糖苷酶抑制剂作用机理的分子动力学模拟和自由能计算[J].物理化学学报，2012， 9（9）：2191-2201.
[30] Berman HM，Westbrook J，Feng Z，et al. The protein data bank [J]. Nucleic Acids Res，2000，28（3）：235-242.
[31] Frank JA，Lorimer D，Youle M，et al. Structure and function of a cyanophage-encoded peptide deformylase [J]. ISME J，2013，7（6）：1150-1160.
[32] Fieulaine S，Boularot A，Artaud I，et al. Trapping conformational states along ligand-binding dynamics of peptide deformylase：the impact of induced fit on enzyme catalysis [J]. PLoS Biol，2011，9（5）：211-218.
[33] Yoon HJ，Kim HL，Lee SK，et al. Crystal structure of peptide deformylase from Staphylococcus aureus in complex with actinonin，a naturally occurring antibacterial agent [J]. Proteins，2004，57（3）：639-642.
[34] Park JK，Kim KH，Moon JH，et al. Characterization of peptide deformylase 2 from B cereus [J]. J Biochem Mol Biol，2007，40（6）：1050-1057.
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