Replacement of valine by tryptophan or tyrosine at position α96 of the α chain (α96Val), located in the α1β 2 subunit interface of hemoglobin leads to low oxygen affinity hemoglobin, and has been suggested to be due to the extra stability introduced by an aromatic amino acid at the α96 position. The characteristic of aromatic amino acid substitution at the α96 of hemoglobin has been further investigated by producing double mutant r Hb (α42Tyr → Phe, α96Val → Trp). r Hb (α42Tyr → Phe) is known to exhibit almost no cooperativity in binding oxygen, and possesses high oxygen affinity due to the disruption of the hydrogen bond between α42Tyr and β99Asp in the α1β2 subunit interface of deoxy Hb A. The second mutation, α96Val → Trp, may compensate the functional defects of r Hb (α42Tyr → Phe), if the stability due to the introduction of trypophan at the α96 position is strong enough to overcome the defect of r Hb (α42Tyr → Phe). Double mutant r Hb (α42Tyr → Phe, α96Val → Trp) exhibited almost no cooperativity in binding oxygen and possessed high oxygen affinity, similarly to that of r Hb (α42Tyr → Phe). 1H NMR spectroscopic data of r Hb (α42Tyr → Phe, α96Val → Trp) also showed a very unstable deoxy-quaternary structure. The present investigation has demonstrated that the presence of the crucible hydrogen bond between α42Tyr and β99Asp is essential for the novel oxygen binding properties of deoxy Hb (α96Val → Trp).
|Number of pages||5|
|Journal||Journal of Biochemistry and Molecular Biology|
|Publication status||Published - 2005 Dec 1|
All Science Journal Classification (ASJC) codes
- Molecular Biology