Non-site-specific allosteric effect of oxygen on human hemoglobin under high oxygen partial pressure.
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.
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.
Masayoshi
M
Takayanagi
Graduate School of Information Science, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8601, Japan.
Ikuo
I
Kurisaki
1] Graduate School of Information Science, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8601, Japan [2] Core Research for Evolutional Science and Technology, Japan Science and Technology Agency, Honmachi, Kawaguchi 332-0012, Japan.
Masataka
M
Nagaoka
D000494:Allosteric Regulation; D000495:Allosteric Site; D001665:Binding Sites; D006418:Heme / Q000378:metabolism*; D006454:Hemoglobins / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D008958:Models, Molecular; D008968:Molecular Conformation; D056004:Molecular Dynamics Simulation; D010100:Oxygen / Q000737:chemistry* / Q000378:metabolism; D010313:Partial Pressure; D011485:Protein Binding; D020836:Protein Structure, Quaternary
D006454:Hemoglobins; D006418:Heme; D010100:Oxygen