Biophysical Reviews

, Volume 10, Issue 2, pp 271–284 | Cite as

A role of heme side-chains of human hemoglobin in its function revealed by circular dichroism and resonance Raman spectroscopy

  • Masako Nagai
  • Naoki Mizusawa
  • Teizo Kitagawa
  • Shigenori Nagatomo


Structural changes of heme side-chains of human adult hemoglobin (Hb A) upon ligand (O2 or CO) dissociation have been studied by circular dichroism (CD) and resonance Raman (RR) spectroscopies. We point out the occurrence of appreciable deformation of heme side-chains like vinyl and propionate groups prior to the out-of-plane displacement of heme iron. Referring to the recent fine resolved crystal structure of Hb A, the deformations of heme side-chains take place only in the β subunits. However, these changes are not observed in the isolated β chain (β4 homotetramer) and, therefore, are associated with the α–β inter-subunit interactions. For the communications between α and β subunits in Hb A regarding signals of ligand dissociation, possible routes are proposed on the basis of the time-resolved absorption, CD, MCD (magnetic CD), and RR spectroscopies. Our finding of the movements of heme side-chains would serve as one of the clues to solve the cooperative O2 binding mechanism of Hb A.


Human hemoglobin Subunits interactions Circular dichroism Resonance Raman Deformations of heme side-chains Cooperative oxygen binding 



We are grateful to the Japanese Red Cross Kanto-Koshinetsu Block Blood Center for the gift of concentrated red cells to advance this human hemoglobin study. This study was supported by a Grant-in-Aid from the Ministry of Education, Culture, Sports, Science, and Technology for Scientific Research (C) to S.N. (17K05606) and Scientific Research (B) to T.K. (24350086), and also by a research grant from the Research Center for Micro-Nano Technology, Hosei University to M.N. and N.M.

Compliance with ethical standards

Conflict of interest

Masako Nagai declares that she has no conflict of interest. Naoki Mizusawa declares that he has no conflict of interest. Teizo Kitagawa declares that he has no conflict of interest. Shigenori Nagatomo declares that he has no conflict of interest.

Ethical approval

This article does not contain any studies with human participants or animals performed by any of the authors.


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© International Union for Pure and Applied Biophysics (IUPAB) and Springer-Verlag GmbH Germany, part of Springer Nature 2017

Authors and Affiliations

  1. 1.Research Center for Micro-Nano TechnologyHosei UniversityKoganeiJapan
  2. 2.School of Health Sciences, College of Medical, Pharmaceutical and Health SciencesKanazawa UniversityKanazawaJapan
  3. 3.Picobiology Institute, Graduate School of Life ScienceUniversity of HyogoAko-gunJapan
  4. 4.Department of Chemistry, Faculty of Pure and Applied SciencesUniversity of TsukubaTsukubaJapan

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