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• W2326269154 abstract "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 IN (NMP domain open while LID domain closed) and IL (LID domain open and NMP domain closed), respectively. Further investigation of temperature effects suggests that the IN pathway is dominant at room temperature, but the IL pathway is dominant at the optimal temperature. This leads us to propose that the IL pathway is more dominant by entropy and IN 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)." @default.
• W2326269154 created "2016-06-24" @default.
• W2326269154 creator A5013799893 @default.
• W2326269154 creator A5019823097 @default.
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• W2326269154 creator A5068298385 @default.
• W2326269154 date "2012-11-13" @default.
• W2326269154 modified "2023-09-27" @default.
• W2326269154 title "Exploring the Dynamic Functional Landscape of Adenylate Kinase Modulated by Substrates" @default.
• W2326269154 cites W1963493131 @default.
• W2326269154 cites W1966078827 @default.
• W2326269154 cites W1968127704 @default.
• W2326269154 cites W1968872901 @default.
• W2326269154 cites W1970454429 @default.
• W2326269154 cites W1973702340 @default.
• W2326269154 cites W1974303276 @default.
• W2326269154 cites W1976051941 @default.
• W2326269154 cites W1976779811 @default.
• W2326269154 cites W1978012161 @default.
• W2326269154 cites W1978741482 @default.
• W2326269154 cites W1979154012 @default.
• W2326269154 cites W1980571928 @default.
• W2326269154 cites W1987679703 @default.
• W2326269154 cites W1988214145 @default.
• W2326269154 cites W1994481437 @default.
• W2326269154 cites W1995894235 @default.
• W2326269154 cites W1997837689 @default.
• W2326269154 cites W2001804099 @default.
• W2326269154 cites W2003180932 @default.
• W2326269154 cites W2007307944 @default.
• W2326269154 cites W2010198013 @default.
• W2326269154 cites W2014425795 @default.
• W2326269154 cites W2017509211 @default.
• W2326269154 cites W2017998155 @default.
• W2326269154 cites W2022394654 @default.
• W2326269154 cites W2022860817 @default.
• W2326269154 cites W2023231003 @default.
• W2326269154 cites W2025021746 @default.
• W2326269154 cites W2031822741 @default.
• W2326269154 cites W2033580831 @default.
• W2326269154 cites W2038100259 @default.
• W2326269154 cites W2040355223 @default.
• W2326269154 cites W2041000185 @default.
• W2326269154 cites W2044626483 @default.
• W2326269154 cites W2046489890 @default.
• W2326269154 cites W2047682506 @default.
• W2326269154 cites W2055497972 @default.
• W2326269154 cites W2056637556 @default.
• W2326269154 cites W2065864578 @default.
• W2326269154 cites W2065919348 @default.
• W2326269154 cites W2066962978 @default.
• W2326269154 cites W2067204014 @default.
• W2326269154 cites W2070021750 @default.
• W2326269154 cites W2072667360 @default.
• W2326269154 cites W2078419867 @default.
• W2326269154 cites W2081555206 @default.
• W2326269154 cites W2082012059 @default.
• W2326269154 cites W2082028745 @default.
• W2326269154 cites W2085928981 @default.
• W2326269154 cites W2086840833 @default.
• W2326269154 cites W2086865609 @default.
• W2326269154 cites W2087631644 @default.
• W2326269154 cites W2094795801 @default.
• W2326269154 cites W2096929343 @default.
• W2326269154 cites W2097081229 @default.
• W2326269154 cites W2098787719 @default.
• W2326269154 cites W2102099014 @default.
• W2326269154 cites W2118180037 @default.
• W2326269154 cites W2120781005 @default.
• W2326269154 cites W2121156878 @default.
• W2326269154 cites W2125213515 @default.
• W2326269154 cites W2127362915 @default.
• W2326269154 cites W2131501854 @default.
• W2326269154 cites W2145920789 @default.
• W2326269154 cites W2149744037 @default.
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• W2326269154 cites W2313401558 @default.
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• W2326269154 doi "https://doi.org/10.1021/ct300720s" @default.
• W2326269154 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/26589012" @default.
• W2326269154 hasPublicationYear "2012" @default.
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