Structure of human carbonmonoxyhemoglobin at 2.16 Å: a snapshot of the allosteric transition

A 2.16 Å resolution structure of high-salt human carbonmonoxyhemoglobin crystallized at pH 6.4 is reported. The quaternary structure is similar to that of `classic' R-state hemoglobin; however, subtle but significant tertiary structural changes are observed at the α₁β₂ and symmetrically equivalent α₂β₁ interfaces – these are the key subunit interfaces that govern the allosteric transition between the R and T states. Specifically, the movement and weakening of two important hydrogen bonds that are diagnostic for R-state structures, β₂His97–α₁Thr38 and β₂Arg40–α₁Thr41, have been observed. In addition, a phosphate molecule bound between the two β-­subunits (at the entrance to the central water cavity) has been identified and electron density indicates that this molecule occupies two alternate positions that are related by the dyad axis. Both positions superimpose on the 2,3-­diphosphoglycerate binding site. One phosphate conformer interacts with β₂Asn139, β₁His143 and β₁His146, while the second interacts with symmetry-related counterparts (β₁Asn139, β₂His143 and β₂His146).