Rate constants for O2 and CO binding to the alpha and beta subunits within the R and T states of human hemoglobin.
Despite a large amount of work over the past 30 years, there is still no universal agreement on the differential reactivities of the individual alpha and beta subunits in human hemoglobin. To address this question systematically, we prepared a series of hybrid hemoglobins in which heme was replaced by chromium(III), manganese(III), nickel(II), and magnesium(II) protoporphyrin IXs in either the alpha or beta subunits to produce alpha2(M)beta2(Fe)1 and alpha2(Fe)beta2(M) tetramers. None of the abnormal metal complexes react with dioxygen or carbon monoxide. The O2 affinities of the resultant hemoglobins vary from 3 microM-1 (Cr(III)/Fe(II) hybrids) to 0.003 microM-1 (Mg(II)/Fe(II) hybrids), covering the full range expected for the various high (R) and low (T) affinity quaternary conformations, respectively, of human hemoglobin A0. The alpha and beta subunits in hemoglobin have similar O2 affinities in both quaternary states, despite the fact that the R to T transition causes significantly different structural changes in the alpha and beta heme pockets. This functional equivalence almost certainly evolved to maintain high n values for efficient O2 transport.
Department of Biophysical Engineering, Faculty of Engineering Science, Osaka University, Toyonaka, Osaka 560, Japan.
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S
Unzai
R
R
Eich
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N
Shibayama
J S
JS
Olson
H
H
Morimoto
D000494:Allosteric Regulation; D002248:Carbon Monoxide / Q000378:metabolism*; D002857:Chromium / Q000737:chemistry / Q000378:metabolism; D006454:Hemoglobins / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D008024:Ligands; D008274:Magnesium / Q000737:chemistry / Q000378:metabolism; D008345:Manganese / Q000737:chemistry / Q000378:metabolism; D009532:Nickel / Q000737:chemistry / Q000378:metabolism; D010100:Oxygen / Q000378:metabolism*; D011487:Protein Conformation; D011524:Protoporphyrins / Q000737:chemistry / Q000378:metabolism
D006454:Hemoglobins; D008024:Ligands; D011524:Protoporphyrins; D002857:Chromium; D008345:Manganese; D009532:Nickel; D002248:Carbon Monoxide; D008274:Magnesium; D010100:Oxygen