Exploring the Dynamic Functional Landscape of Adenylate Kinase Modulated by Substrates
文献类型：期刊论文
| 作者 | Wang Y ; Gan LF ; Wang EK ; Wang J |
| 刊名 | journal of chemical theory and computation
 |
| 出版日期 | 2013 |
| 卷号 | 9期号:1页码:84-95 |
| 关键词 | CONFORMATIONAL TRANSITIONS ENERGY LANDSCAPE INDUCED-FIT ESCHERICHIA-COLI MOLECULAR-DYNAMICS LIGAND-BINDING DOMAIN CLOSURE NETWORK MODEL PROTEIN MECHANISM |
| ISSN号 | 1549-9618 |
| 通讯作者 | wang j |
| 中文摘要 | adenylate kinase (adk) has been explored widely, through both experimental and theoretical studies. however, still less is known about how the functional dynamics of adk is modulated explicitly by its natural substrates. here, we report a quantitative study of the dynamic energy landscape for adk responding to the substrate binding by integrating both experimental investigations and theoretical modeling. we make theoretical predictions which are in remarkable agreement with the single molecule experiments on the substrate-bound complex. with our combined models of adk in its apo form, in the presence of amp or atp, and in complex with both substrates, we specifically address the following key questions: (1) are there intermediate state(s) during their catalytic cycle and if so how many? (2) how many pathways are there along the open-to-closed transitions and what are their corresponding weights? (3) how do substrates influence the pathway weights and the stability of the intermediates? (4) which lid's motion is rate-limiting along the turnover cycle, the nmp or the lid domain? our models predict two major parallel stepwise pathways and two on-pathway intermediates which are denoted as i-n (nmp domain open while lid domain closed) and i-l (lid domain open and nmp domain closed), respectively. further investigation of temperature effects suggests that the i-n pathway is dominant at room temperature, but the i-l pathway is dominant at the optimal temperature. this leads us to propose that the i-l pathway is more dominant by entropy and i-n pathway by enthalpy. remarkably, our results show that even with maximum concentrations of natural substrates, adk still fluctuates between multiple functional states, reflecting an intrinsic capability of large-scale conformational fluctuations which may be essential to its biological function. the results based on the dual-ligands model provide the theoretical validation of random bisubstrate biproducts (bi-bi) mechanism for the enzymatic reaction of adk additionally, the pathway flux analysis strongly suggests that the motion of the nmp domain is the rate-determining step for the conformational cycle (opening and closing). |
| 收录类别 | SCI收录期刊论文 |
| 语种 | 英语 |
| WOS记录号 | WOS:000313378700012 |
| 公开日期 | 2014-04-18 |
| 源URL | [http://ir.ciac.jl.cn/handle/322003/50392]  |
| 专题 | 长春应用化学研究所_长春应用化学研究所知识产出_期刊论文 |
| 推荐引用方式 GB/T 7714 | Wang Y,Gan LF,Wang EK,et al. Exploring the Dynamic Functional Landscape of Adenylate Kinase Modulated by Substrates[J]. journal of chemical theory and computation,2013,9(1):84-95. |
| APA | Wang Y,Gan LF,Wang EK,&Wang J.(2013).Exploring the Dynamic Functional Landscape of Adenylate Kinase Modulated by Substrates.journal of chemical theory and computation,9(1),84-95. |
| MLA | Wang Y,et al."Exploring the Dynamic Functional Landscape of Adenylate Kinase Modulated by Substrates".journal of chemical theory and computation 9.1(2013):84-95. |
入库方式： OAI收割
来源：长春应用化学研究所
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