The type IA topoisomerase catalytic cycle: A normal mode analysis and molecular dynamics simulation

doi:10.1002/prot.21876

	The type IA topoisomerase catalytic cycle: A normal mode analysis and molecular dynamics simulation
	Xiong, Bing1,2 ; Burk, David L.2; Shen, Jianhua1 ; Luo, Xiaomin1 ; Liu, Hong1 ; Shen, Jingkang 1; Berghuis, Albert M.2
刊名	PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS
	2008-06
卷号	71 期号:4 页码:1984-1994
关键词	topoisomerase III normal mode steered molecular dynamics correlation map protein-DNA interaction MM-PBSA
ISSN号	0887-3585
DOI	10.1002/prot.21876
文献子类	Article
英文摘要	Type LA topoisomerases alter the topological state Of DNA to relax the supercoils introduced during the DNA replication and transcription process, giving them critical roles in many cellular functions. To manipulate the DNA, type IA topoisomerases first cleave one DNA strand and form a covalent linkage between a catalytic tyrosine residue and the 5'-phosphoryl of the DNA. This is followed by a movement of domain III of the topoisomerase to accommodate the second DNA strand in the center channel of the topoisomerase. Domain III is then closed for religation of the cleaved DNA and subsequently reopened to release the passing strand. Although numerous biophysical and biochemical studies have examined this catalytic cycle, fundamental questions remain such as how domain III opens and closes during this process. We have used computational simulation methods, namely normal mode analysis and molecular dynamics, to investigate the catalytic cycle of Escherichia coli topoisomerase III as a representative of the type LA topoisomerases. It was found that domain II is intrinsically flexible and may empower the enzyme to perform its function by triggering domain III opening and closing. A molecular dynamics simulation and MM-PBSA analysis shows that topoisomerase III alone cannot overcome the large energy barrier of the conformational transition. A detailed examination of the DNA binding sites suggests that the processing DNA cooperates with the topoisomerase to accomplish this dramatic conformational change. These findings will guide future mutagenesis studies of type LA topoisomerases aimed at dissecting the driving forces and conformations in the catalytic cycle.
WOS关键词	DNA TOPOISOMERASES ; CONFORMATIONAL-CHANGES ; MECHANISM ; ENERGY ; MINIMIZATION ; PROTEINS ; BINDING ; STRAND
WOS研究方向	Biochemistry & Molecular Biology ; Biophysics
语种	英语
出版者	WILEY-LISS
WOS记录号	WOS:000255920600031
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/272914]
专题	药物化学研究室中科院受体结构与功能重点实验室新药研究国家重点实验室
通讯作者	Shen, Jingkang
作者单位	1.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China; 2.McGill Univ, Dept Biochem, Quebec City, PQ H3A 1A4, Canada
推荐引用方式 GB/T 7714	Xiong, Bing,Burk, David L.,Shen, Jianhua,et al. The type IA topoisomerase catalytic cycle: A normal mode analysis and molecular dynamics simulation[J]. PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS,2008,71(4):1984-1994.
APA	Xiong, Bing.,Burk, David L..,Shen, Jianhua.,Luo, Xiaomin.,Liu, Hong.,...&Berghuis, Albert M..(2008).The type IA topoisomerase catalytic cycle: A normal mode analysis and molecular dynamics simulation.PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS,71(4),1984-1994.
MLA	Xiong, Bing,et al."The type IA topoisomerase catalytic cycle: A normal mode analysis and molecular dynamics simulation".PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS 71.4(2008):1984-1994.