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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
2
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pubmed:dateCreated |
2002-7-18
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pubmed:abstractText |
The molecular basis of the "tail helix latch" hypothesis in the gelsolin activation process has been studied by using the steered molecular dynamics simulations. In the present nanosecond scale simulations, the tail helix of gelsolin was pulled away from the S2 binding surface, and the required forces were calculated, from which the properties of binding between the tail helix and S2 domain and their dynamic unbinding processes were obtained. The force profile provides a detailed rupture mechanism that includes six major unbinding steps. In particular, the hydrogen bonds formed between Arg-207 and Asp-744 and between Arg-221 and Leu-753 are of the most important interaction pairs. The two hydrogen bond "clamps" stabilize the complex. The subsequent simulation on Arg-207-Ala (R207A) mutation of gelsolin indicated that this mutation facilitates the unbinding of the tail helix and that the contribution of the hydrogen bond between Arg-207 and Asp-744 to the binding is more than 50%, which offers a new clue for further mutagenesis study on the activation mechanism of gelsolin. Surrounding water molecules enhance the stability of the tail helix and facilitate the rupture process. Additionally, temperature also has a significant effect on the conformation of the arginine and arginine-related interactions, which revealed the molecular basis of the temperature dependence in gelsolin activation.
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/12124262-10047530,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12124262-10559185,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12124262-10583954,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12124262-10819996,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12124262-10862770,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12124262-11297932,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12124262-11997278,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12124262-2541138,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12124262-2836434,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12124262-2850369,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12124262-3020431,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12124262-3021782,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12124262-7630882,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12124262-8182748,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12124262-8584939,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12124262-875032,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12124262-9288746,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12124262-9398317,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12124262-9631289,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12124262-9826629
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Aug
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pubmed:issn |
0006-3495
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
83
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
753-62
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pubmed:dateRevised |
2009-11-18
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pubmed:meshHeading |
pubmed-meshheading:12124262-Arginine,
pubmed-meshheading:12124262-Aspartic Acid,
pubmed-meshheading:12124262-Gelsolin,
pubmed-meshheading:12124262-Hydrogen Bonding,
pubmed-meshheading:12124262-Leucine,
pubmed-meshheading:12124262-Models, Molecular,
pubmed-meshheading:12124262-Protein Binding,
pubmed-meshheading:12124262-Protein Conformation,
pubmed-meshheading:12124262-Protein Structure, Tertiary,
pubmed-meshheading:12124262-Temperature
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pubmed:year |
2002
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pubmed:articleTitle |
Steered molecular dynamics simulations on the "tail helix latch" hypothesis in the gelsolin activation process.
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pubmed:affiliation |
Center for Drug Discovery and Design, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 294 Taiyuan Road, Shanghai 200031, Peoples Republic of China.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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