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Korean Society for Biochemistry and Molecular Biology (생화학분자생물학회)
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Characteristic of Aromatic Amino Acid Substitution at α96 of Hemoglobin

  • Choi, Jong-Whan (Department of Biochemistry, Department of Parasitology and Institute of Basic Medical Sciences, Yonsei University Wonju College of Medicine) ;
  • Lee, Jong-Hyuk (Department of Opthalmology, Department of Parasitology and Institute of Basic Medical Sciences, Yonsei University Wonju College of Medicine) ;
  • Lee, Kwang-Ho (Department of Anesthesiology and Pain Medicine, Department of Parasitology and Institute of Basic Medical Sciences, Yonsei University Wonju College of Medicine) ;
  • Lee, Hyean-Woo (Department of Biochemistry, Department of Parasitology and Institute of Basic Medical Sciences, Yonsei University Wonju College of Medicine) ;
  • Sohn, Joon-Hyung (Department of Biochemistry, Department of Parasitology and Institute of Basic Medical Sciences, Yonsei University Wonju College of Medicine) ;
  • Yoon, Joon-Ho (Department of Biochemistry, Department of Parasitology and Institute of Basic Medical Sciences, Yonsei University Wonju College of Medicine) ;
  • Yeh, Byung-Il (Department of Biochemistry, Department of Parasitology and Institute of Basic Medical Sciences, Yonsei University Wonju College of Medicine) ;
  • Park, Seung-Kyu (Department of Biochemistry, Department of Parasitology and Institute of Basic Medical Sciences, Yonsei University Wonju College of Medicine) ;
  • Lee, Kyu-Jae (Department of Biochemistry, Department of Parasitology and Institute of Basic Medical Sciences, Yonsei University Wonju College of Medicine) ;
  • Kim, Hyun-Won (Department of Biochemistry, Department of Parasitology and Institute of Basic Medical Sciences, Yonsei University Wonju College of Medicine)
  • Published : 2005.01.31
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Abstract

Replacement of valine by tryptophan or tyrosine at position $\alpha$96 of the $\alpha$ chain ($\alpha$96Val), located in the ${\alpha}_1{\beta}_2$ 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 $\alpha$96 position. The characteristic of aromatic amino acid substitution at the $\alpha$96 of hemoglobin has been further investigated by producing double mutant r Hb ($\alpha$42Tyr$\rightarrow$ Phe, $\alpha$96Val$\rightarrow$Trp). r Hb ($\alpha$42Tyr$\rightarrow$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 $\alpha$42Tyr and $\beta$99Asp in the ${\alpha}_1{\beta}_2$ subunit interface of deoxy Hb A. The second mutation, $\alpha$96Val$\rightarrow$Trp, may compensate the functional defects of r Hb ($\alpha$42Tyr$\rightarrow$Phe), if the stability due to the introduction of trypophan at the $\alpha$96 position is strong enough to overcome the defect of r Hb ($\alpha$42Tyr$\rightarrow$Phe). Double mutant r Hb ($\alpha$42Tyr$\rightarrow$Phe, $\alpha$96Val$\rightarrow$Trp) exhibited almost no cooperativity in binding oxygen and possessed high oxygen affinity, similarly to that of r Hb ($\alpha$42Tyr$\rightarrow$Phe). $^1$H NMR spectroscopic data of r Hb ($\alpha$42Tyr$\rightarrow$Phe, $\alpha$96Val$\rightarrow$Trp) also showed a very unstable deoxy-quaternary structure. The present investigation has demonstrated that the presence of the crucible hydrogen bond between $\alpha$42Tyr and $\beta$99Asp is essential for the novel oxygen binding properties of deoxy Hb ($\alpha$96Val$\rightarrow$Trp).

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References

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