• Masayoshi Takayanagi, Ikuo Kurisaki, and Masataka Nagaoka.
• 1] Venture Business Laboratory, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8601, Japan [2] Graduate School of Information Science, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8601, Japan [3] Core Research for Evolutional Science and Technology, Japan Science and Technology Agency, Honmachi, Kawaguchi 332-0012, Japan.
• Sci Rep. 2014 Apr 8; 4: 4601.

AbstractProtein 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.

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