@article{b5228bfd2c7d46aa9e19f3db8fe0d338,
title = "Non-site-specific allosteric effect of oxygen on human hemoglobin under high oxygen partial pressure",
abstract = "Protein allostery is essential for vital activities. Allosteric regulation of human hemoglobin (HbA) with two quaternary states T and R has been a paradigm of allosteric structural regulation of proteins. It is widely accepted that oxygen molecules (O2) act as a ''site-specific'' homotropic effector, or the successive O2 binding to the heme brings about the quaternary regulation. However, here we show that the site-specific allosteric effect is not necessarily only a unique mechanism of O2 allostery. Our simulation results revealed that the solution environment of high O2 partial pressure enhances the quaternary change from T to R without binding to the heme, suggesting an additional ''non-site-specific'' allosteric effect of O2. The latter effect should play a complementary role in the quaternary change by affecting the intersubunit contacts. This analysis must become a milestone in comprehensive understanding of the allosteric regulation of HbA from the molecular point of view.",
author = "Masayoshi Takayanagi and Ikuo Kurisaki and Masataka Nagaoka",
note = "Funding Information: This work was partially supported by a Grant-in-Aid for the 21st Century COE program {\textquoteleft}{\textquoteleft}Frontiers of Computational Science{\textquoteright}{\textquoteright} at Nagoya University and also by a Grant-in-Aid for Science Research from the Ministry of Education, Culture, Sport, Science and Technology in Japan and the Core Research for Evolutional Science and Technology (CREST) {\textquoteleft}{\textquoteleft}Creation of Innovative Functional Materials with Advanced Properties by Hyper-nano-space Design{\textquoteright}{\textquoteright} and {\textquoteleft}{\textquoteleft}Establishment of Molecular Technology towards the Creation of New Functions{\textquoteright}{\textquoteright} from the Japan Science and Technology Agency. I.K., also thanks for the support from Japan Society for the Promotion of Science (JSPS) by the Research Fellowship for Young Scientist.",
year = "2014",
month = apr,
day = "8",
doi = "10.1038/srep04601",
language = "English",
volume = "3",
journal = "Scientific Reports",
issn = "2045-2322",
publisher = "Nature Publishing Group",
}