Open AccessThe α1β1 contact of human hemoglobin plays a key role in stabilizing the bound dioxygen
Author(s) -
Yasuda Jun pei,
Ichikawa Takayuki,
Tsuruga Mie,
Matsuoka Ariki,
Sugawara Yoshiaki,
Shikama Keiji
Publication year - 2002
Publication title -
european journal of biochemistry
Language(s) - English
Resource type - Journals
eISSN - 1432-1033
pISSN - 0014-2956
DOI - 10.1046/j.0014-2956.2002.02635.x
Subject(s) - autoxidation , tetramer , chemistry , valency , ferric , beta (programming language) , crystallography , stereochemistry , catalysis , nucleophile , dimer , hemoglobin , medicinal chemistry , photochemistry , inorganic chemistry , organic chemistry , philosophy , linguistics , computer science , programming language , enzyme
When the α and β chains were separated from human oxyhemoglobin (HbO 2 ), each individual chain was oxidized easily to the ferric form, their rates being almost the same with a very strong acid‐catalysis. In the HbO 2 tetramer, on the other hand, both chains become considerably resistant to autoxidation over a wide range of pH values (pH 5–11). Moreover, HbA showed a biphasic autoxidation curve containing the two rate constants, i.e. k f for the fast oxidation due to the α chains, and k s for the slow oxidation to the β chains. The k f / k s ratio increased from 3.2 at pH 7.5–7.3 at pH 5.8, but became 1 : 1 at pH values higher than 8.5. In the present work, we used the valency hybrid tetramers such as (α 3+ ) 2 (βΟ 2 ) 2 and (αΟ 2 ) 2 (β 3+ ) 2 , and demonstrated that the autoxidation rate of either the α or β chains (when O 2 ‐ligated) is independent of the valency state of the corresponding counterpart chains. From these results, we have concluded that the formation of the α1β1 or α2β2 contact suppresses remarkably the autoxidation rate of the β chain and thus plays a key role in stabilizing the HbO 2 tetramer. Its mechanistic details were also given in terms of a nucleophilic displacement of O 2 – from the FeO 2 center, and the emphasis was placed on the proton‐catalyzed process performed by the distal histidine residue.