2017年9月
In silico analyses of the effects of a point mutation and a pharmacological chaperone on the thermal fluctuation of phenylalanine hydroxylase
BIOPHYSICAL CHEMISTRY
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- 巻
- 228
- 号
- 開始ページ
- 47
- 終了ページ
- 54
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.1016/j.bpc.2017.06.014
- 出版者・発行元
- ELSEVIER SCIENCE BV
Phenylketonuria (PKU) is an inborn error of phenylalanine metabolism due to mutations in phenylalanine hydroxylase (PAH). Recently, small compounds, known as pharmacological chaperones (PhCs), have been identified that restore the enzymatic activity of mutant PAHs. Understanding the mechanism of the reduction in enzymatic activity due to a point mutation in PAH and its restoration by PhC binding is important for the design of more effective PhC drugs. Thermal fluctuations of an enzyme can alter its activity. Here, molecular dynamics simulation show the thermal fluctuation of PAH is increased by introduction of the A313T mutation. Moreover, a simulation using the A313T-PhC complex model was also performed. Thermal fluctuation of the mutant was found to be reduced upon PhC binding, which contributes to restoring its enzymatic activity.
- リンク情報
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- DOI
- https://doi.org/10.1016/j.bpc.2017.06.014
- Web of Science
- https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000407980700006&DestApp=WOS_CPL
- URL
- http://www.scopus.com/inward/record.url?eid=2-s2.0-85021892023&partnerID=MN8TOARS
- URL
- http://orcid.org/0000-0003-0566-4669
- ID情報
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- DOI : 10.1016/j.bpc.2017.06.014
- ISSN : 0301-4622
- eISSN : 1873-4200
- ORCIDのPut Code : 36301377
- SCOPUS ID : 85021892023
- Web of Science ID : WOS:000407980700006