Functional and spectroscopic characterization of half-liganded iron - Zinc hybrid hemoglobin: Evidence for conformational plasticity within the T state

Uri Samuni, Laura Juszczak, David Dantsker, Imran Khan, Adam J. Friedman, José Pérez-González-de-Apodaca, Stefano Bruno, Hilda L. Hui, Judith E. Colby, Ellen Karasik, Laura D. Kwiatkowski, Andrea Mozzarelli, Robert Noble, Joel M. Friedman

Research output: Contribution to journalArticle

45 Scopus citations

Abstract

Functionally distinct conformations of HbA (human adult hemoglobin) were probed using deoxy and diliganded derivatives of symmetric Fe - Zn hybrids of HbA. To expand the range of accessible structures, different environments were utilized including solution, sol - gel encapsulation, and crystals. Further structural and functional modulation was achieved by the addition of allosteric effectors. Functional characterization included oxygen affinity measurements, CO combination rates, and geminate and bimolecular CO recombination, after photodissociation. The conformational properties were studied using visible resonance Raman spectroscopy as a probe of local tertiary structure at the iron-containing hemes and UV resonance Raman spectroscopy as a probe of elements of the globin known to be sensitive to quaternary structure. The combined results show a pattern in which there is a progression of conformational and functional properties that are consistent with a picture in which the T quaternary structure can accommodate a range of tertiary conformations (plasticity). At one end of the distribution is the equilibrium deoxy T state conformation that has the lowest ligand reactivity. At the other end of the distribution are T state conformations with higher ligand reactivity that exhibit "loosened" T state constraints within the globin including the α1β2 interface and reduced proximal strain at the heme.

Original languageEnglish (US)
Pages (from-to)8272-8288
Number of pages17
JournalBiochemistry
Volume42
Issue number27
DOIs
StatePublished - Jul 15 2003

ASJC Scopus subject areas

  • Biochemistry

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    Samuni, U., Juszczak, L., Dantsker, D., Khan, I., Friedman, A. J., Pérez-González-de-Apodaca, J., Bruno, S., Hui, H. L., Colby, J. E., Karasik, E., Kwiatkowski, L. D., Mozzarelli, A., Noble, R., & Friedman, J. M. (2003). Functional and spectroscopic characterization of half-liganded iron - Zinc hybrid hemoglobin: Evidence for conformational plasticity within the T state. Biochemistry, 42(27), 8272-8288. https://doi.org/10.1021/bi020648j