期刊
PLOS ONE
卷 7, 期 7, 页码 -出版社
PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pone.0040700
关键词
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资金
- Direccion General Asuntos del Personal Academico (DGAPA)
- Universidad nacional autonoma de Mexico (UNAM)
- Programa de Apoyo a Proyectos de Investigacion e Innovacion Tecnologica (PAPIIT) [204611]
- Consejo Nacional de Ciencia y Tecnologia (CONACyT) [102370, 128156]
- Program of Postdoctoral Scholarships from DGAPA (UNAM)
Molecular dynamic (MD) simulations have been performed on Tth-MCO, a hyperthermophilic multicopper oxidase from thermus thermophilus HB27, in the apo as well as the holo form, with the aim of exploring the structural dynamic properties common to the two conformational states. According to structural comparison between this enzyme and other MCOs, the substrate in process to electron transfer in an outer-sphere event seems to transiently occupy a shallow and overall hydrophobic cavity near the Cu type 1 (T1Cu). The linker connecting the beta-strands 21 and 24 of the second domain (loop (beta 21-beta 24)(D2)) has the same conformation in both states, forming a flexible lid at the entrance of the electron-transfer cavity. Loop (beta 21-beta 24)(D2) has been tentatively assigned a role occluding the access to the electron-transfer site. The dynamic of the loop (beta 21-beta 24)(D2) has been investigated by MD simulation, and results show that the structures of both species have the same secondary and tertiary structure during almost all the MD simulations. In the simulation, loop (beta 21-beta 24)(D2) of the holo form undergoes a higher mobility than in the apo form. In fact, loop (beta 21-beta 24)(D2) of the holo form experiences a conformational change which enables exposure to the electron-transfer site (open conformation), while in the apo form the opposite effect takes place (closed conformation). To confirm the hypothesis that the open conformation might facilitate the transient electron-donor molecule occupation of the site, the simulation was extended another 40 ns with the electron-donor molecule docked into the protein cavity. Upon electron-donor molecule stabilization, loops near the cavity reduce their mobility. These findings show that coordination between the copper and the protein might play an important role in the general mobility of the enzyme, and that the open conformation seems to be required for the electron transfer process to T1Cu.
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